Effects of thioether substituents on the O2 reactivity of β-diketiminate-Cu(I) complexes: Probing the role of the methionine ligand in copper monooxygenases

Article abstract of DOI:10.1021/ja057745v

The activation of dioxygen by dopamine β-monooxygenase (DβM) and peptidylglycine α-hydroxylating monooxygenase (PHM) is postulated to occur at a copper site ligated by two histidine imidazoles and a methionine thioether, which is unusual because such thio

Full text of DOI:10.1021/ja057745v

Published on Web 02/15/2006
Effects of Thioether Substituents on the O2 Reactivity of
â-Diketiminate-Cu(I) Complexes: Probing the Role of the
Methionine Ligand in Copper Monooxygenases
Nermeen W. Aboelella, Benjamin F. Gherman, Lyndal M. R. Hill, John T. York,
Nicole Holm, Victor G. Young, Jr., Christopher J. Cramer, and William B. Tolman*
Contribution from the Department of Chemistry, Center for Metals in Biocatalysis, and
Minnesota Supercomputer Institute, UniVersity of Minnesota, 207 Pleasant Street SE,
Minneapolis, Minnesota 55455
Received November 23, 2005; E-mail: tolman@chem.umn.edu
Abstract: The activation of dioxygen by dopamine â-monooxygenase (DâM) and peptidylglycine R-hy-
droxylating monooxygenase (PHM) is postulated to occur at a copper site ligated by two histidine imidazoles
and a methionine thioether, which is unusual because such thioether ligation is not present in other O2-
activating copper proteins. To assess the possible role of the thioether ligand in O2 activation by DâM and
PHM, two new ligands comprising â-diketiminates with thioether substituents were synthesized and Cu(I)
and Cu(II) complexes were isolated. The Cu(II) compounds are monomeric and exhibit intramolecular
thioether coordination. While the Cu(I) complexes exhibit a multinuclear topology in the solid state, variable-
temperature 1H NMR studies implicate equilibria in solution, possibly including monomers with intramolecular
thioether coordination that are structurally defined by DFT calculations. Low-temperature oxygenation of
solutions of the Cu(I) complexes generates stable 1:1 Cu/O2 adducts, which on the basis of combined
experimental and theoretical studies adopt side-on “η2” structures with negligible Cu-thioether bonding
and significant peroxo-Cu(III) character. In contrast to previously reported findings with related ligands
lacking the thioether group, however (cf., Aboelella; et al. J. Am. Chem. Soc. 2004, 126, 16896), purging
the solutions of the thioether-containing adducts with argon results in conversion to bis(µ-oxo)dicopper(III)
species. A role for the thioether in promoting loss of O2 from the 1:1 Cu/O2 adduct and facilitating trapping
of the resulting Cu(I) complex to yield the bis(µ-oxo) species is proposed, and the possible relevance of
this role to that of the methionine in the active sites of DâM and PHM is discussed.
Introduction
of C-H bonds (of dopamine or peptide glycine terminus,
respectively) to produce physiologically significant metabolites
The binding and activation of dioxygen by copper centers is
critically important in biology1 and catalysis.2 In proteins, such
reactions often occur at active sites with multiple copper ions,3
and studies of model complexes have provided extensive insight
into the nature of relevant multicopper-O2 species.4 The
coordination and reduction of O2 also occurs at single Cu sites
in proteins,5 as exemplified by dopamine â-monooxygenase
(DâM)5,6 and peptidylglycine R-hydroxylating monooxygenase
(PHM).5,7 These enzymes perform stereospecific hydroxylations
(norepinephrine or R-amidated peptide). X-ray crystallographic
data on PHM8 and X-ray absorption spectroscopy on DâM9 and
PHM10 have revealed that these similar proteins contain two
copper ions separated by ∼11 Å, one with three imidazolyl
ligands (CuH) and the other with two imidazoles and a thioether
(CuM) provided by the respective histidine or methionine side
(4) (a) Mirica, L. M.; Ottensaelder, X.; Stack, T. D. P. Chem. ReV. 2004, 104,
1013. (b) Lewis, E. A.; Tolman, W. B. Chem. ReV. 2004, 104, 1047. (c)
Hatcher, L.; Karlin, K. D. J. Biol. Inorg. Chem. 2004, 9, 669. (d) Itoh, S.;
Fukuzumi, S. Bull. Chem. Soc. Jpn. 2002, 75, 2081. (e) Kopf, M.-A.; Karlin,
K. D. In Biomimetic Oxidations Catalyzed by Transition Metal Complexes;
Meunier, B., Ed.; Imperial College Press: London, 2000; pp 309-362. (f)
Schindler, S. Eur. J. Inorg. Chem. 2000, 2311. (g) Blackman, A. G.;
Tolman, W. B. Struct. Bonding (Berlin) 2000, 97, 179.
(5) (a) Klinman, J. P. Chem. ReV. 1996, 96, 2541. (b) Halcrow, M. A. In
ComprehensiVe Coordination Chemistry II; McCleverty, J. A., Meyer, T.
J., Eds.; Elsevier: Amsterdam, 2004; Vol. 8, pp 395-436.
(6) Stewart, L. C.; Klinman, J. P. Annu. ReV. Biochem. 1988, 57, 551.
(7) Eipper, B. A.; Stoffers, D. A.; Mains, R. E. Annu. ReV. Neurosci. 1992,
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(1) Selected recent reviews: (a) Solomon, E. I.; Sundaram, U. M.; Machonkin,
T. E. Chem. ReV. 1996, 96, 2563. (b) Solomon, E. I.; Chen, P.; Metz, M.;
Lee, S.-K.; Palmer, A. E. Angew. Chem., Int. Ed. 2001, 40, 4570. (c) Itoh,
S. In ComprehensiVe Coordination Chemistry II; McCleverty, J. A., Meyer,
T. J., Eds.; Elsevier: Amsterdam, 2004; Vol. 8, pp 369-393. (d) Lee, D.-
H.; Lucchese, B.; Karlin, K. D. In ComprehensiVe Coordination Chemistry
II; McCleverty, J. A., Meyer, T. J., Eds.; Elsevier: Amsterdam, 2004; Vol.
8, pp 437-457. (e) Halcrow, M. A.; Knowles, P. F.; Phillips, S. E. V. In
Handbook on Metalloproteins; Bertini, I., Sigel, A., Sigel, H., Eds.; Marcell
Dekker: New York, 2001; Chapter 15, pp 709-762.
(2) For recent examples, see: (a) Kirillov, A. M.; Kopylovich, M. N.; Kirillova,
M. V.; Haukka, M.; da Silva, M. F. C. G.; Pombeiro, A. J. L. Angew.
Chem., Int. Ed. 2005, 44, 4345 and references therein. (b) Marko´, I. E.;
Gautier, A.; Dumeunier, R.; Doda, K.; Philippart, F.; Brown, S. M.; Urch,
C. J. Angew. Chem., Int. Ed. 2004, 43, 1588.
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Lindley, P. F. Dalton Trans. 2005, 3507.
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S. T.; Eipper, B. A.; Mains, R. E.; Amzel, L. M. Science 2004, 304, 864.
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J. AM. CHEM. SOC. 2006, 128, 3445-3458
3445

A R T I C L E S
Aboelella et al.
Figure 2. Structurally characterized 1:1 Cu/O2 adducts.18,19 Ad ) ada-
mantyl.
Figure 1. The copper sites in PHM as determined by X-ray crystallography.8a
The water molecules on CuH are not shown. CuM is the presumed site of
dioxygen binding and reduction and is located ∼11.5 Å from CuH.
such species have been isolated and subjected to structural,
spectroscopic, and theoretical characterization. The best char-
acterized are similar insofar as they feature sterically hindered
N-donor ligands and side-on “η2” coordination of the O2 moiety
(Figure 2), but they differ with respect to their electronic
structures.18-20 Complex 1 is best formulated as a Cu(II)-
superoxide species,18b,20a whereas the strong electron-donating
capabilities of the â-diketiminate [(R2LiPr2)-, R ) Me or tBu]21
or anilido-imine ligands in 2a and 2b, respectively, underly
significant Cu(III)-peroxide character in these complexes.19,20
chains (Figure 1). Various evidence supports the notion that
O2 coordinates to CuM during the enzymes’ catalytic cycles,9b,10b
including an X-ray crystal structure of an end-on CuM-O2
adduct generated when a reduced Cu(I) form of PHM was
treated with O2 in the presence of a slow substrate.8c Recently
proposed mechanisms invoke this or related CuM-O2 adducts
as the species directly responsible for attacking the C-H bond
of the substrate, although there are differences of opinion
regarding later reaction steps.11-14
The steric bulk of (R2LiPr2 -
is critical for isolation of 2a,
)
The binding and activation of O2 at a Cu(I) center supported
by a thioether ligand as proposed for DâM and PHM is unusual,
because such thioether ligation is not present in other O2-
activating copper proteins1 and is instead typically associated
with “type 1” electron-transfer sites.15 Several different roles
for the methionine ligand in catalysis by DâM and PHM have
been suggested. For example, preferential stabilization of the
Cu(I) state of CuM by the methionine ligand has been proposed
to increase the driving force for electron transfer from CuH to
CuM.8b Such stabilization of the Cu(I) state has also been
suggested to decrease the equilibrium constant for O2 binding
to CuM, thus preventing “leakage” of reactive oxygen intermedi-
ates by ensuring that O2 reduction does not occur in the absence
of substrate.11,12 These notions are supported by the observation
by EXAFS10c and theory12 of a shorter CuM-S(Met) bond
distance in the Cu(I) form relative to the Cu(II) state. It has
also been hypothesized that the methionine ligand stabilizes a
putative Cu(II)M-oxyl intermediate, which is suggested to form
after C-H bond activation by the CuM-O2 species.12 These
proposals for the role of the methionine ligand are intuitively
appealing, yet they are provocative and deserve testing.
In synthetic chemistry, examples of thioether coordination
in complexes of Cu(I) and Cu(II) abound,16 but in no case have
Cu(I) complexes with thioether ligands been found to yield
isolable Cu/O2 intermediates upon oxygenation.17 Mononuclear
Cu/O2 complexes are typically only observed as transient
intermediates in rapid kinetics studies due to their tendency to
form peroxo- and/or bis(µ-oxo)dicopper complexes,4 but a few
because reducing the size of the arene substituents instead results
in the generation of bis(µ-oxo)dicopper complexes.19a,22 The
binding of O2 to Me2LiPr2Cu(MeCN) to yield 2a is irreversible
at low temperature, such that purging solutions with argon
removes free O2 but does not perturb 2a, thus allowing it to be
used subsequently in reactions with other reduced metal species
to generate dicopper complexes with different supporting ligands
on each metal and/or heterobimetallic complexes.19b,23 While
complexes 1 and 2 represent important models of how O2
coordination to a single copper site in a protein might occur,
both lack the thioether coordination implicated in DâM and
PHM.
We hypothesized that replacement of one of the isopropyl
substituents in (Me2LiPr2 -
) with a thioether appendage would
yield a ligand that provides the N2S(thioether) donor set found
in DâM and PHM. Moreover, we envisioned that a 1:1 Cu/O2
adduct supported by such a N2S(thioether) donor set (akin to
(17) The following are examples of air-sensitive Cu(I) complexes with thioether
ligands that nonetheless do not yield isolable Cu/O2 intermediates: (a)
Casella, L.; Gullotti, M.; Bartosek, M.; Pallanza, G.; Laurenti, E. J. Chem.
Soc., Chem. Commun. 1991, 1235. (b) Champloy, F.; Benali-Cherif, N.;
Bruno, P.; Blain, I.; Pierrot, M.; Reglier, M.; Michalowicz, A. Inorg. Chem.
1998, 37, 3910.
(18) (a) Fujisawa, K.; Tanaka, M.; Moro-oka, Y.; Kitajima, N. J. Am. Chem.
Soc. 1994, 116, 12079. (b) Chen, P.; Root, D. E.; Campochiaro, C.;
Fujisawa, K.; Solomon, E. I. J. Am. Chem. Soc. 2003, 125, 466.
(19) (a) Spencer, D. J. E.; Aboelella, N. W.; Reynolds, A. M.; Holland, P. L.;
Tolman, W. B. J. Am. Chem. Soc. 2002, 124, 2108. (b) Aboelella, N. W.;
Lewis, E. A.; Reynolds, A. M.; Brennessel, W. W.; Cramer, C. J.; Tolman,
W. B. J. Am. Chem. Soc. 2002, 124, 10660. (c) Aboelella, N. W.; Kryatov,
S. V.; Gherman, B. F.; Brennessel, W. W.; Young, V. G., Jr.; Sarangi, R.;
Rybak-Akimova, E. V.; Hodgson, K. O.; Hedman, B.; Solomon, E. I.;
Cramer, C. J.; Tolman, W. B. J. Am. Chem. Soc. 2004, 126, 16896. (d)
Reynolds, A. M.; Gherman, B. F.; Cramer, C. J.; Tolman, W. B. Inorg.
Chem. 2005, 44, 6989.
(10) (a) Eipper, B. A.; Quon, A. S. W.; Mains, R. E.; Boswell, J. S.; Blackburn,
N. J. Biochemistry 1995, 34, 2857. (b) Boswell, J. S.; Reddy, B. J.;
Kulathila, R.; Merkler, D.; Blackburn, N. J. Biochemistry 1996, 35, 12241.
(c) Blackburn, N. J.; Rhames, F. C.; Ralle, M.; Jaron, S. J. Biol. Inorg.
Chem. 2000, 5, 341.
(11) Evans, J. P.; Ahn, K.; Klinman, J. P. J. Biol. Chem. 2003, 278, 49691.
(12) Chen, P.; Solomon, E. I. J. Am. Chem. Soc. 2004, 126, 4991.
(13) Kamachi, T.; Kihara, N.; Shiota, Y.; Yoshizawa, K. Inorg. Chem. 2005,
44, 4226.
(14) Gherman, B. F.; Heppner, D. E.; Tolman, W. B.; Cramer, C. J. J. Biol.
Inorg. Chem. 2006, 11, in press.
(20) (a) Cramer, C. J.; Tolman, W. B.; Theopold, K. H.; Rheingold, A. L. Proc.
Natl. Acad. Sci. U.S.A. 2003, 100, 3635. (b) Gherman, B. F.; Cramer, C.
J. Inorg. Chem. 2004, 43, 7281.
(21) Ligand abbreviations used here are similar to those described previously.22
Thus, (R2LR′,R′′ - refers to a â-diketiminate where R refers to the R-backbone
)
substituents and R′ and R′′ refer to the ortho substituents on the aryl ring.
Thus, in 2a for R ) Me, the ligand is (Me2LiPr2)-. For simplicity, we denote
the more asymmetric ligands in Scheme 1 as (Me2LiPr,SMe - or (Me2LiPr,SPh)-.
)
(22) Spencer, D. J. E.; Reynolds, A. M.; Holland, P. L.; Jazdzewski, B. A.;
Duboq-Toia, C.; Pape, L. L.; Yokota, S.; Tachi, Y.; Itoh, S. Inorg. Chem.
2002, 41, 6307.
(15) (a) Gray, H. B.; Malmstrom, B. G.; Williams, R. J. P. J. Biol. Inorg. Chem.
2000, 551. (b) Randall, D. W.; Gamelin, D. R.; LaCroix, L. B.; Solomon,
E. I. J. Biol. Inorg. Chem. 2000, 5, 16.
(23) Aboelella, N. W.; York, J. T.; Reynolds, A. M.; Fujita, K.; Kinsinger, C.
R.; Cramer, C. J.; Riordan, C. G.; Tolman, W. B. Chem. Commun. 2004,
1716.
(16) (a) Bouwman, E.; Driessen, W. L.; Reedijk, J. Coord. Chem. ReV. 1990,
104, 143. (b) Zanello, P. Comments Inorg. Chem. 1988, 8, 45.
9
3446 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

Effects of Thioether Substituents on O2 Reactivity
A R T I C L E S
The synthesis of Me2LiPr,SMeH was problematic, as the
condensation reaction afforded a mixture of the desired product
and the symmetric species Me2LiPr2H and Me2LSMe2H according
to 1H and 13C{1H} NMR spectroscopy and mass spectrometry.
The ratio of these products was ∼45:45:10 (1H NMR) and could
be improved to ∼6:3:1 by crystallization of the crude product
Scheme 1
n
from EtOH. Treatment of the mixture with BuLi resulted in
the selective precipitation of Li(Me2LiPr,SMe) that was subse-
quently used for the preparation of copper complexes (see
below).
Notable features of the 1H NMR spectra of the â-diketimines
Me2LiPr,SXH (X ) Me or Ph) include a singlet at ∼12.5 ppm
corresponding to the -NH proton and an AB pattern for the
diastereotopic methylene protons of the thioether arm (e.g., for
R ) Me, δ ) 3.68 and 3.58 ppm, J ) 13.2 Hz). For
Li(Me2LiPr,SMe), the -NH resonance is absent and the chemical
shift difference between the thioether methylene resonances
increases significantly to ∼0.5 ppm, with two doublets observed
(an AX pattern). Similarly, large differences in the chemical
shifts of the diastereotopic methylene hydrogens were observed
in the copper complexes of the ligands (see below).
Synthesis and Characterization of Cu(II) Complexes.
Copper(II) complexes of the ligands (Me2LiPr,SX)- were prepared
to probe the coordinating ability of the thioether appendage, in
particular to assess whether intramolecular binding would occur
to an oxidized copper site such as that which would be formed
upon oxygenation of a Cu(I) precursor. Using procedures
analogous to those reported previously for the preparation of
[LCuCl]n (L ) â-diketiminate, n ) 1 or 2),19a,22,28,29 solutions
of the lithium salts Li(Me2LiPr,SX) in THF were added to a slurry
of CuCl2‚0.8THF in THF (Scheme 1). The dark purple
complexes Me2LiPr,SXCuCl were isolated in modest yields
(∼50%) after crystallization from toluene/pentane mixtures at
-20 °C.
the proposed reactive species in the enzymes) would be
accessible, given the precedent provided by the O2 chemistry
of Me2LiPr2Cu(MeCN)19a-c and the steric bulk provided by the
three remaining ortho-isopropyl group substituents of the new
ligands. Studies of such an adduct would enable comparisons
with 2 aimed at discerning the role of the thioether in dioxygen
binding and activation. Herein, we report the synthesis of two
variants of this new ligand, characterization of their complexes
with Cu(I) and Cu(II) that demonstrate thioether binding to the
metal, and the results of experimental and theoretical studies
of the oxygenation reactions of the Cu(I) complexes. Through
this work, important effects of the thioether group on the Cu(I)/
O2 chemistry have been identified that are relevant to the
possible role of the methionine ligand in O2 activation by DâM
and PHM.24
Results and Discussion
Ligand Synthesis and Characterization. The â-diketimines
Me2LiPr,SXH (X ) Me or Ph; Scheme 1) were targeted for use
as precursors of â-diketiminate ligands for coordination to Cu(I)
and Cu(II) ions. In addition to containing ortho isopropyl
substituents that we hoped would sterically favor monocopper
complex formation, the ligands feature a methylene linker
between the phenyl ring and the thioether sulfur that would result
in the formation of a favorable six-membered chelate ring upon
intramolecular binding of the thioether to a coordinated metal
ion. We prepared Me2LiPr,SXH (R ) Me or Ph) by condensing
the thioether-substituted anilines 3 (X ) Me, known;25 X )
Ph, prepared by an analogous procedure26) with 2-(2,6-diiso-
propylphenylimido)-2-pentene-4-one27 (Scheme 1). The com-
pound Me2LiPr,SPhH was isolated as an analytically pure,
crystalline solid in modest yield (33%) and was fully character-
ized, including by X-ray diffraction (Figure S1, Supporting
Information). Deprotonation of Me2LiPr,SPhH with nBuLi to yield
the â-diketiminate Li(Me2LiPr,SPh) was possible (1H NMR), but
isolation of the product was hindered by its high solubility in
organic solvents. Thus, we used either freshly prepared crude
solutions of Li(Me2LiPr,SPh) or the precursor Me2LiPr,SPhH itself
to prepare copper complexes (see below).
The X-ray crystal structures of both Cu(II) complexes indicate
that they are monomeric species in the solid state (Figure 3).
This observation attests to a degree of steric bulk imposed by
(Me2LiPr,SX - that is similar to that of (Me2LiPr2)-, which
)
supports a 3-coordinate monomeric geometry in Me2LiPr2CuCl.28
Other â-diketiminates with smaller arene and/or backbone
substituents yield chloride-bridged dimeric structures, [LCu(µ-
Cl)]2, in the solid state.29 The thioether sulfur atom is bound to
the Cu(II) center in both complexes, with a Cu-S bond distance
of 2.3793(11) Å in Me2LiPr,SMeCuCl and 2.5941(9) Å in
Me2LiPr,SPhCuCl, which contains the more bulky phenyl group
on the thioether arm. These Cu(II)-thioether bond distances
fall within the range of such distances reported previously
(2.28-2.91 Å, avg ) 2.41 Å).30 The thioether coordination
results in a significant distortion of the copper geometry away
from the trigonal planar topology of Me2LiPr2CuCl,28 such that
the chloride ligand lies below the N-Cu-N plane (by 30.1° or
24.7° for X ) Me or Ph, respectively) and has a longer bond to
the Cu(II) ion (X ) Me, 2.218(1) Å; X ) Ph, 2.1846(9) Å)
than in the 3-coordinate complex (2.127(1) Å). Overall, the
distorted tetrahedral geometries in the complexes Me2LiPr,SX
-
(24) Aspects of this work are reported in: Aboelella, N. W. Ph.D. Thesis,
University of Minnesota, 2005.
(25) Teramoto, S.; Tanaka, M.; Shimizu, H.; Fujioka, T.; Tabusa, F.; Imaizumi,
T.; Yoshida, K.; Fujiki, H.; Mori, T.; Sumida, T.; Tominaga, M. J. Med.
Chem. 2003, 46, 3033.
(26) (a) Gassman, P. G.; Gruetzmacher, G. D. J. Am. Chem. Soc. 1974, 96,
5487. (b) Gassman, P. G.; Drewes, H. R. J. Am. Chem. Soc. 1974, 96,
3002.
(27) Dove, A. P.; Gibson, V. C.; Marshall, E. L.; White, A. J. P.; Williams, D.
J. Dalton Trans. 2004, 570.
(28) Holland, P. L.; Tolman, W. B. J. Am. Chem. Soc. 1999, 121, 7270.
(29) Jazdzewski, B. A.; Holland, P. L.; Pink, M.; Young, V. G., Jr.; Spencer,
D. J. E.; Tolman, W. B. Inorg. Chem. 2001, 40, 6097.
(30) From a search of the Cambridge Crystallographic Database, CSDversion
5.26 (November 2004). Values for Cu(II) systems are based on 92 structures
and 217 Cu-S distances; for Cu(I) systems, they are based on 109 structures
and 344 Cu-S distances.
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3447

A R T I C L E S
Aboelella et al.
The UV-vis spectra of Me2LiPr,SXCuCl in CH2Cl2 resemble
that reported previously for Me2LiPr2CuCl,28 clearly indicating
that the complexes exist as monomers in solution, yet suggesting
that the thioether group dissociates to yield 3-coordinate species
(Figure S3). This latter conclusion remains tentative, however,
in view of the subtle differences between the spectra (cf., the
extinctions and widths of the near-IR feature) and the potential
complications from the presence of backbone-chlorinated byprod-
ucts.
Synthesis and Characterization of Cu(I) Complexes.
Complexes of (Me2LiPr,SX)- with Cu(I) were prepared either by
mixing Li(Me2LiPr,SMe) with CuCl or by reaction of Me2LiPr,SPh
H
32
with (Me3SiCH2Cu)4 in THF (Scheme 1). The products
correspond to the empirical formula Me2LiPr,SXCu according to
analytical data (CHN analysis, high-resolution mass spectrom-
etry). In the case of the complex with (Me2LiPr,SMe)-, addition
of 1 equiv of PPh3 yielded a monomeric adduct, Me2LiPr,SMe
-
Cu(PPh3). This adduct and its precursor Cu(I) complex were
characterized by X-ray crystallography (Figure 4).
In contrast to the monomeric structures observed for the
Cu(II) complexes Me2LiPr,SXCuCl, the Cu(I) complex of
(Me2LiPr,SMe -
) crystallizes as a tetramer, in which only one-
half of the molecule is unique, and the other half is grown by
symmetry through an inversion center. Rather than binding to
the copper center to which its N-donors are bound (i.e., in
intramolecular fashion), the thioether arm of each ligand binds
to the copper center of the adjacent Me2LiPr,SMeCu fragment.33
The lack of any intramolecular Cu-S interaction is confirmed
by distances from the copper centers to the thioether sulfurs of
the same ligand that includes its N-donors that are all greater
than 3.77 Å. The intermolecular Cu(I)-S distances of ∼2.16
Å are considerably shorter than the Cu-S distances observed
in the Cu(II)-chloride complexes discussed above (∼2.38 and
2.59 Å), a typical phenomenon27b,34,35 that may be rationalized
by hard-soft acid-base considerations (favorable interaction
of the soft thioether sulfur donor and the low-valent d10 Cu(I)
center). In a survey of the Cambridge Crystallographic Structural
Data Centre for Cu-S bond distances in Cu(I)-thioether
complexes, the average bond distance is 2.31 Å over a range
of 2.19-2.88 Å, as compared to the average Cu-S distance of
2.41 Å for Cu(II)-thioether complexes.30 Thus, the Cu(I)-
thioether bond distances here lie toward the short end of the
range for Cu(I) complexes, indicating relatively strong binding
Figure 3. Representations of the X-ray structures of (a) LiPr,SMeCuCl and
(b) LiPr,SPhCuCl. All atoms are shown as 50% thermal ellipsoids, with
hydrogen atoms omitted for clarity. Selected interatomic distances (Å) and
angles (deg) are as follows: (a) Cu1-N1, 1.906(3); Cu1-N2, 1.956(3);
Cu1-Cl1, 2.2177(11); Cu1-S1, 2.3793(11); N1-Cu1-N2, 94.26(13); N1-
Cu1-S1, 92.67(10); N2-Cu1-Cl1, 105.29(9); S1-Cu1-Cl1, 95.78(4).
(b) Cu1-N1, 1.888(2); Cu1-N2, 1.934(2); Cu1-Cl1, 2.1846(9); Cu1-
S1, 2.5941(9); N1-Cu1-N2, 94.42(10); N1-Cu1-S1, 89.48(8); N2-
Cu1-Cl1, 108.59(8); S1-Cu1-Cl1, 100.27(3).
CuCl bear some resemblance to that in the thiolate-thioether
model of oxidized type 1 “blue” copper centers, Me2LiPr2Cu-
(SCPh2CH2SMe), where the Cu(II)-S(thioether) distance is
2.403(1) Å (Figure S2).31
In the structures of both complexes, unexpected electron
density was found near the ligand backbone carbon C3 that was
too significant to be considered residual. Given the distance from
C3 (1.685(11) Å for X ) Me and 1.708(3) Å for X ) Ph), the
density was best modeled as a chlorine atom at partial
occupancy. This compositional disorder refined to a 90:10 ratio
of hydrogen:chlorine occupancy for R ) Me and a 53:47 ratio
for X ) Ph (Figure 3b). Corroborating these assignments, high-
resolution mass spectra of the complexes showed peaks at-
tributable to the parent ions both for Me2LiPr,SXCuCl and for
the backbone-chlorinated versions (see Experimental Section).
The source of the partial chlorination of the ligand backbone is
likely the CuCl2‚0.8THF reagent. However, the mechanism for
the chlorination is unknown, and such a reaction has not been
observed in previously reported â-diketiminate Cu(II)-chloride
complexes.29 Despite the compositional disorder at C3, there is
no further disorder in the X-ray structures and the R1 values of
0.0566 for X ) Me and 0.0472 for X ) Ph indicate good quality
crystal data. Most importantly, there is no disorder in the
thioether arm, and thus in the solid state, intramolecular binding
of the thioether sulfur to the Cu(II) center occurs in both the
non-chlorinated and the chlorinated species.
of the thioether arm. Nonetheless, upon reaction of [Me2LiPr,SMe
-
Cu]4 with PPh3, the thioether arm is displaced to yield a
monomeric 3-coordinate complex, Me2LiPr,SMeCu(PPh3) (Figure
4b). The Cu-N and Cu-P bond distances in this compound
are similar to those observed for the previously reported complex
Me2LiPr2Cu(PPh3).36 Finally, although the crystal structure of
(32) (a) Lappert, M. F.; Pearce, R. Chem. Commun. 1973, 24-2. (b) Jarvis, J.
A.; Kilbourn, B. T.; Pearce, R.; Lappert, M. F. Chem. Commun. 1973,
475. (c) Jarvis, J. A.; Pearce, R.; Lappert, M. F. J. Chem. Soc., Dalton
Trans. 1977, 999.
(33) Similar “intermolecular” coordination of thioether groups in oligomeric
Cu(I) complexes has been reported. See: (a) Yim, H. W.; Tran, L. M.;
Pullen, E. E.; Rabinovich, D. Inorg. Chem. 1999, 38, 6234. (b) Tanaka,
R.; Yano, T.; Nishioka, T.; Nakajo, K.; Breedlove, B. K.; Kimura, K.;
Kinoshita, I.; Isobe, K. Chem. Commun. 2002, 1686.
(34) Ambundo, E. A.; Deydier, M.-V.; Grall, A. J.; Aguera-Vega, N.; Dressel,
L. T.; Cooper, T. H.; Heeg, M. J.; Ochrymowycz, L. A.; Rorabacher, D.
B. Inorg. Chem. 1999, 38, 4233.
(35) Ohta, T.; Tachiyama, T.; Yoshizawa, K.; Yamabe, T.; Uchida, T.; Kitagawa,
T. Inorg. Chem. 2000, 39, 4358.
(36) Reynolds, A. M.; Lewis, E. A.; Aboelella, N. W.; Tolman, W. B. Chem.
Commun. 2005, 2014.
(31) Holland, P. L.; Tolman, W. B. J. Am. Chem. Soc. 2000, 122, 6331.
9
3448 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

Effects of Thioether Substituents on O2 Reactivity
A R T I C L E S
Figure 6. Selected region of the variable-temperature 1H NMR spectra of
Me2LiPr,SPhCu (THF-d8, 300 MHz) with assignments indicated (see text).
Å. Increasing the Cu-S distance leads to geometries with
steadily increasing electronic energies (Figure S4). At a Cu-S
distance of 3.0 Å, where the thioether may be considered
dissociated from Cu, the electronic energy has risen by 7.2 kcal/
mol. Increases in the Cu-S distance also correlate with
decreasing Wiberg Cu-S bond indices (Figure S5).37,38 Thus,
although the X-ray crystal structures reveal multinuclear species
for the Cu(I) complexes in the solid state, the DFT calculations
suggest that if a mononuclear species were accessible (e.g., in
solution), thioether binding would be favored.
Figure 4. Representations of the X-ray structures of (a) [Me2LiPr,SMeCu]4
and (b) Me2LiPr,SMeCu(PPh3). All atoms are shown as 50% thermal ellipsoids,
with hydrogen atoms omitted for clarity. The isopropyl groups in [Me2LiPr,SMe
-
Cu]4 also are omitted to facilitate visualization of the structure. Selected
interatomic distances (Å) and angles (deg) are as follows: (a) Cu1-N1,
1.928(3); Cu1-N2, 1.953(3); Cu1-S1, 2.1637(9); Cu2-N3, 1.963(3);
Cu2-N4, 1.935(2); Cu2-S2, 2.1581(8); N1-Cu1-N2, 98.90(11); N1-
Cu1-S1, 132.19(8); N2-Cu1-S1, 128.88(8); N3-Cu2-N4, 99.05(11);
N3-Cu2-S2, 123.72(8); N4-Cu2-S2, 136.41(8). (b) Cu1-N1, 1.956-
(3); Cu1-N2, 1.950(3); Cu1-P1, 2.1687(11); N1-Cu1-N2, 98.52(14);
N1-Cu1-P1, 128.28(11); N2-Cu1-P1, 132.66(10).
To probe the structures of the Cu(I) complexes in solution,1H
NMR spectra were recorded in different solvents (C6D6 or THF-
d8) and at various temperatures. The VT-NMR spectra recorded
between 25 and -85 °C in THF-d8 for Me2LiPr,SXCu (X ) Me
or Ph) are similar (Figures S6 and S7). Particularly revealing
portions of the spectra for Me2LiPr,SPhCu are shown with
assignments in Figure 6. At 25 °C, a singlet (“a”) is observed
for the central -CH on the ligand backbone at 4.74 ppm that
suggests the presence of a single species at this temperature.
However, the pattern for the diastereotopic thioether methylene
-CH2 protons at 3.9-4.1 ppm (“b”) deviates from that expected
for an AB or AX system, insofar as the upfield peaks are
broadened considerably more than the downfield set. We assign
this spectrum to a single molecule (species A) that participates
in a fluxional process (“high T process”) that affects one of the
diastereotopic protons more than the other, such that at 25 °C
they exhibit different line widths. Upon cooling, the intensity
Figure 5. Minimum energy structure for Me2LiPr,SMeCu determined from
DFT calculations, with metal-ligand bond distances indicated and hydrogen
atoms omitted for clarity.
Me2LiPr,SPhCu was not obtained, given its spectroscopic similari-
ties to Me2LiPr,SMeCu (vide infra), it is likely that it also displays
a similar multinuclear topology in the solid state.
In addition to X-ray crystallography, DFT calculations were
performed to determine the minimum energy structure for
Me2LiPr,SMeCu (Figure 5). Although the calculations do not
address the possibility of higher nuclearity species, they predict
that the preferred structure for a monomeric complex includes
the thioether bound to the copper with a Cu-S distance of 2.301
(37) Glendening, E. D.; Badenhoop, J. K.; Reed, A. E.; Carpenter, J. E.;
Bohmann, J. A.; Morales, C. M.; Weinhold, F. (Theoretical Chemistry
Institute, University of Wisconsin, Madison, WI, 2001); http://www.
chem.wisc.edu/∼nbo5.
(38) Wiberg, K. B. Tetrahedron 1968, 24, 1083.
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3449

A R T I C L E S
Aboelella et al.
ref
Table 1. Selected Spectroscopic Properties of Cu(I) Complexes and Cu/O2 Intermediatesa
1
1 b
complex
UV
−vis:
λ
max, nm (
ꢀ
, M-1 cm-
)
Raman (cm-
)
Me2LiPr,SMeCu(I)
Me2LiPr,SPhCu(I)
Me2LiPr,SMeCuO2
255 (sh, 16 700), 280 (sh, 13 600), 357 (18 200), 382 (16 400)
255 (sh, 15 600), 275 (sh, 13 300), 360 (16 300), 382 (15 200)
332 (26 700), 395 (sh, 2000), 610 (200)
this work
this work
this work
990/971c
991/969 (925)d
994/971c
Me2LiPr,SMeCuO2
331 (28 500), 395 (sh, 2000), 595 (200)
this work
994/970 (925)d
968 (917)e
961 (912)e
974 (908)e
592 (567)g
593 (567)g
604 (577)g
Me2LiPr2CuO2 (2a, R ) Me)
tBu2LiPr2CuO2 (2a, R ) tBu)
2b
385 (∼2400), 600 (200)
424 (2000), 638 (200)
390 (sh, 7600), 440 (10 300), 453 (11 300), 650 (200)
448 (∼11 000)f
19a
19b
19d
this work
this work
22
[(Me2LiPr,SMeCu)2(µ-O)2]
[(Me2LiPr,SPhCu)2(µ-O)2]
[(Me2LEt2Cu)2(µ-O)2]
443 (∼6000)f
426 (10 000)f
a Except as noted, all UV-vis and resonance Raman spectra were measured in THF, with extinction coefficients reported per copper. UV-vis spectra
were obtained at -80 °C, and resonance Raman spectra were obtained at -196 °C. b Reported as Raman shifts for samples prepared with 16O2 (18O2).
c ν(O-O), THF, λex ) 406.7 nm, data for compound prepared from 18O2 unavailable due to spectral overlap with a solvent peak. d ν(O-O), CH2Cl2, λex
406.7 nm. e ν(O-O), acetone, λex ) 413.1 nm. f Extinction coefficient reported per bis(µ-oxo)dicopper complex. g ν(Cu2O2), λex ) 457.9 nm.
)
of the central -CH peak at 4.74 ppm decreases while a new
-CH singlet appears at 4.83 ppm (“a”). Concurrently, the peaks
due to the thioether methylene -CH2 protons centered at 4 ppm
decrease in intensity, while two new doublets for these protons
grow in at vastly different chemical shifts (4.23 and 3.03 ppm,
J ) 18.6 Hz, “b”). The multiplets attributed to the isopropyl
substituent methine -CH protons (3.2-3.4 ppm, “c”) also
change upon cooling, but to multiple broad signals that
precluded definitive assignment.
1
We interpret the changes in the H NMR spectrum upon
cooling to indicate that the species present at higher temperature
Figure 7. UV-vis spectra in THF at -80 °C of Me2LiPr,SMeCu (dotted
line), the product of its oxygenation (solid line), and the species resulting
after purging the oxygenation product solution with argon (dashed line).
(species A) equilibrates with a second species (B) that has a
structure sufficiently different from that of A to effect a major
change in the chemical shift difference between the diaste-
reotopic thioether methylene protons.39 Within the rubric of this
hypothesis, we estimated equilibrium constants (Keq ) [B]/[A])
at each temperature by integrating the singlets for the ligand
backbone -CH protons and obtained thermodynamic parameters
from a plot of ln(Keq) versus 1/T (Figure S8): ∆H° ) -18.3(5)
kJ mol-1 and ∆S° ) -82(4) J mol-1 K-1. Although definitive
structural assignments for species A and B are not possible to
obtain with the available data, the large chemical shift difference
between the thioether methylene signals in species B and the
significantly negative entropy value for its equilibration with
species A are consistent with B being an oligomeric species
with intermolecular thioether coordination akin to that of
[Me2LiPr,SMeCu]4 identified in the crystalline state. Accordingly,
we postulate that species A is a monomeric species such as
that defined by theory (Figure 5) and that the “high T process”
discussed above entails rapid coordination and decoordination
of the thioether arm, perhaps with involvement of THF solvent.
Notwithstanding the necessarily tentative nature of these
particular structural hypotheses, it is clear that the Cu(I)
°C in THF or toluene lead to significant changes in the electronic
absorption spectra (Figure 7, for X ) Me). Upon oxygenation,
the yellow Cu(I) solution becomes bright green, a shift in the
high energy π-π* transitions occurs, and a very slight shoulder
appears at ∼395 nm for both complexes, along with a less
intense broad feature at ∼600 nm. The oxygenated solutions
are EPR silent. The UV-vis absorption features degrade upon
warming the solutions to room temperature, indicating the
formation of thermally unstable intermediates. The similarity
of these spectroscopic features to those observed for the
previously reported systems R2LiPr2CuO2 (R ) Me or tBu, Table
1)19b suggests that related 1:1 Cu/O2 adducts are formed in the
thioether-appended ligand system.
Resonance Raman spectroscopy was used to further charac-
terize the oxygenation intermediates. Initial data for the species
prepared with 16O2 were acquired using THF solutions (λex
)
)
406.7 nm, Table 1), but a peak derived from solvent (929 cm-1
obscured the key region of the spectrum in samples prepared
using 18O2. To observe Raman features for both 16O2- and 18O2-
derived samples, we therefore examined the low-temperature
oxygenations of Me2LiPr,SXCu in CH2Cl2. At room temperature,
solutions of the Cu(I) complexes in CH2Cl2 showed signs of
decay within minutes, presumably due to a chlorination reaction
similar to that which has been described for other Cu(I)
compounds.40 Nevertheless, by working quickly the oxygenation
complexes of (Me2LiPr,SX -
undergo fluxional processes in
)
solution that involve significant changes in the chemical
environment of the thioether arm. These changes are most
consistent with alterations in the mode of copper coordination
by the thioether group.
Oxygenation Reactions of Cu(I) Complexes: 1:1 Cu/O2
Adducts. The reactions of Me2LiPr,SXCu with dioxygen at -80
(40) (a) Osako, T.; Karlin, K. D.; Itoh, S. Inorg. Chem. 2005, 44, 410. (b)
Lucchese, B.; Humphreys, K. J.; Lee, D.-H.; Incarvito, C. D.; Sommer, R.
D.; Rheingold, A. L.; Karlin, K. D. Inorg. Chem. 2004, 43, 5987. (c)
Jacobson, R. R.; Tyekla´r, Z.; Karlin, K. D. Inorg. Chim. Acta 1991, 181,
111.
(39) The UV-vis spectra of Me2LiPr,SRCu in THF also change upon cooling
(data not shown), consistent with the hypothesis of equilibria between
multiple species in solution. These data do not allow structural assignments
to be determined, however.
9
3450 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

Effects of Thioether Substituents on O2 Reactivity
A R T I C L E S
Figure 8. Resonance Raman spectra with O-isotope sensitive peaks labeled of frozen solutions (77 K) of (a) the product of the reaction of Me2LiPr,SMeCu
in CH2Cl2 with 16O2 (solid line) or 18O2 (dashed line), using λex ) 406.7 nm, and (b) the species resulting from argon purging of the oxygenation product
Me2LiPr,SMeCuO2 obtained using 16O2 (solid line) or 18O2 (dashed line), using λex ) 457.9 nm.
Table 2. Computed DFT/CASPT2 Free Energies (kcal/mol) for
reactions could be performed without significant decomposition
of the Cu(I) precursors. The UV-vis and resonance Raman data
in CH2Cl2 were similar to those obtained in THF, with the added
benefit of being able to observe new peaks in the spectrum
acquired on the samples prepared with 18O2. The data are shown
in Figures 8a (X ) Me) and S9 (X ) Ph), with all oxygen-
isotope sensitive features listed in Table 1. For both complexes,
two peaks at ∼970 and ∼992 cm-1 shift to a single peak at
925 cm-1 upon 18O substitution. These peaks are in the same
region as the O-O stretching vibration identified in 2,19
suggesting an analogous assignment. In addition, weak features
at 489 cm-1 (X ) Me) or 494 cm-1 (X ) Ph) are also 18O-
isotope sensitive (∆18O ≈ 14 cm-1); these are consistent with
Cu-O vibrations. We hypothesize that the two O-isotope-
sensitive bands in the 16O2 spectrum between 970 and 992 cm-1
are Fermi doublets arising from coupling of the O-O stretch
to a harmonic of the low-frequency feature.41 In support of this
notion, the second overtone (2ν) of the low-frequency feature
is 978 cm-1 (X ) Me) or 988 cm-1 (X ) Ph), in close
agreement with the average of the two observed peaks, 980 cm-1
(X ) Me) or 982 cm-1 (X ) Ph). In line with the hypothesis
of a Fermi doublet, the coupling disappears in the 18O2 spectrum
because in this case 2ν is ∼958 cm-1, far from the ν(18O-18O)
at 925 cm-1. Finally, on the basis of the observed Raman shift
for the 18O-18O stretch (925 cm-1), the calculated 16O-16O
stretch should appear at 981 cm-1 (∆18O2(calc) ) 56 cm-1),
which closely matches the average of the doublets. Taken
together, the data are most consistent with a ν(16O-16O) for
both complexes at ∼981 cm-1 that appears as a doublet due to
Fermi coupling to the second overtone of the ν(Cu-16O) at
Me2LiPr,SMeCuO2 Relative to the η2 Singlet Case
gas phase
THF
80
25
°
C
−
°
C
η1 singlet
η1 triplet
η2 singlet
η2 triplet
7.0
18.4
0.0
6.0
19.8
0.0
15.0
16.4
Figure 9. Minimum energy structures calculated using DFT of (a)
Me2LiPr,SMeCuO2 and (b) [(Me2LH,SMeCu)2(µ-O)2] (hydrogen atoms omitted
for clarity, with distances in Å). Selected distances for the structure in (b)
are: Cu-Cu, 2.926 Å; O-O, 2.301 Å; Cu-O, 1.86 Å; Cu-S, 4.84 Å.
Me2LiPr,SMeCu has effectively dissociated and the Cu-S distance
has increased by 0.7 Å to 3.033 Å (Figure 9a). Further increasing
this interatomic distance leads to a steady but minimal increase
(<1 kcal/mol) in energy (Figure S10). Decreasing the Cu-S
separation back to that observed in Me2LiPr,SMeCu leads to a
much sharper increase in energy; in particular, at 2.30 Å, the
electronic energy is increased by 11 kcal/mol. This result can
be contrasted with the optimized structure for the end-on adduct,
in which the thioether remains ligated to Cu at a distance of
2.550 Å (Figure S11). A structure similar to the side-on case in
which the Cu-S bond is severed occurs at a local minimum
with an electronic energy higher by 1.3 kcal/mol and a Cu-S
distance of ∼2.95 Å (Figure S12). Comparison of the end-on
and side-on structures reveals that if one were to move from
the former to the latter (η1 f η2 isomerization) a steric clash
between the thioether group and the oxygen atom distal from
the Cu center develops, which rationalizes the longer Cu-S
distance in the side-on case. In addition, the significant Cu-
(III)-peroxo character (vide infra) of the side-on adduct would
disfavor axial ligation of the thioether due to the bonding
preferences of the d8 metal center.
∼493 cm-1
.
The similarity of the UV-vis features and ν(O-O) values
for the oxygenation products of Me2LiPr,SXCu to those of 2a
and 2b (Table 1) comprises strong evidence that they exhibit
analogous side-on (η2) O2 coordination. Further insight was
provided by DFT/CASPT2 calculations, which concluded the
side-on singlet Cu-O2 adduct to be most stable among the
singlet and triplet end-on and side-on possibilities for Me2LiPr,SMe
-
CuO2 (Table 2). The triplet cases are distinctly higher in energy
than the corresponding singlets and will not be discussed any
further here. For the η2 adduct, the Cu-S bond present in
(41) Czernuszewicz, R. S.; Spiro, T. G. In Inorganic Electronic Structure and
Spectroscopy Vol. 1, Methodology; Solomon, E. I., Lever, A. B. P., Eds.;
John Wiley & Sons: New York, 1999; pp 353-441.
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3451

A R T I C L E S
Aboelella et al.
Table 3. Computed and Experimentally Determined ν(O-O) and
ν(Cu-O) (cm-1) for the Singlet States of Me2LiPr,SMeCuO2
essentially identical once the Cu-S ligation is removed. The
slight asymmetry that is present with regard to Cu-O distances
in Me2LiPr,SMeCuO2 can be attributed to the steric effect of the
thioether appendage, which causes the proximal Cu-O bond
to be 0.016 Å longer than the distal counterpart (Figure 9a).
On the other hand, the η1 Me2LiPr,SMeCuO2 isomer is ∼3 kcal/
mol less stable versus the η2 isomer as compared to the
corresponding difference in 2a. This occurs despite the presence
of the Cu-S bond in the η1 Me2LiPr,SMeCuO2 isomer, which
confers 1.3 kcal/mol of stability to this structure (cf., Figures
S11, S12). Instead, the difference is attributable to the spatial
proximity of the thioether to the dioxygen moiety, which forces
O2 to bind at an angle (i.e., the difference in N-Cu-O bond
angles is 52.4°), decreasing the favorable orbital overlap between
the Cu d and O2 π* orbitals in the Cu/O2 bonding molecular
orbital (Figure S14).
vibration
16O
−
16O
∆(
18O
−
16O)a
∆(
16O
−
18O)a
∆( −
18O 18O)
η1 computed
η2 computed
O-O
O-O
1194.6
1055.7
981
437.2
461.4
489
36.2
29.3
n/a
19
4.7
n/a
35.9
29.2
n/a
16.8
4.6
70.7
59.9
56
20.0
13.5
14
experimental O-O
η1 computed
η2 computed
experimental Cu-O
Cu-O
Cu-O
n/a
a The first O is the oxygen having the shortest distance to Cu.
Comparison of the computed and experimental O-O and
Cu-O stretch frequencies in the 1:1 adducts (Table 3) shows
that the calculated side-on structure is most consistent with the
experimental ν(16O2) and ∆ν(18O2) data. Although the calculated
ν(O-O) values of the mixed-label isotopomers (i.e., 16O-18O
vs 18O-16O) are nearly identical in the η2 structure, as would
be expected with a symmetrically coordinated O2 ligand, the
results are similar in the asymmetrically bound η1 case. These
findings are in agreement with previous work that has shown
that using isotopomeric splitting to differentiate end-on and side-
on coordination is problematic.42,43
As has been concluded for the 1:1 adducts 2a and 2b,19c,d
the side-on Me2LiPr,SMeCuO2 structure lies intermediate along
the continuum20 between the Cu(II)-superoxo and Cu(III)-
peroxo extremes, although somewhat closer to the peroxo limit.
This conclusion is based upon a collective assessment of the
geometric, vibrational, and electronic data for the structure. The
O-O bond length of 1.354 Å is nearly the average of the ∼1.3
and ∼1.4 Å distances associated with superoxide and peroxide,
respectively. The vibrational frequencies characteristic of su-
peroxo ligands (1075-1200 cm-1) and peroxo ligands (790-
930 cm-1) also frame the computed and experimental ν(O-O)
values. Occupation numbers from the CAS calculation for the
two orbitals that most contribute to the multideterminantal
character of the side-on adduct (Figure S13) are 1.64 and 0.39
and imply that the structure lies approximately two thirds of
the way toward Cu(III)-peroxo.44
Reactivity of the 1:1 Cu/O2 Adducts. (a) Argon Purging.
While the above evidence suggests that the thioether substituent
does not appreciably affect the electronic structure and O2
coordination mode relative to the complexes 2a and 2b, other
evidence indicates that it does influence the thermodynamics
of dioxygen binding. Whereas the formation of 2a and 2b is
irreversible, such that free dioxygen may be removed from
solutions of these complexes without degradation, prolonged
and vigorous bubbling of argon through O2-saturated THF or
toluene solutions of Me2LiPr,SXCuO2 at -80 °C resulted in a
color change from bright green to yellow-brown and develop-
ment of an intense UV-vis absorption feature at ∼445 nm
(Figure 7). The rate of formation of the yellow-brown species
is highly dependent on the rate of argon bubbling through the
solution (faster rate with more rapid bubbling); conversion was
not observed if the bubbling was gentle or performed for only
a short time. The ∼445 nm feature decays upon warming the
solutions to room temperature, indicating that it arises from a
thermally unstable species, and closely resembles a signature
absorption band of the bis(µ-oxo)dicopper(III) core. Diagnostic
features for this core were also observed in resonance Raman
spectra (THF, λex ) 457.9 nm, 77 K) obtained for samples
prepared with 16O2 or 18O2 (Figures 8b (X ) Me) and S15 (X
) Ph)). For example, for X ) Me, we observed a band at 592
cm-1 with ∆18O ) 25 cm-1 (Table 1), which are typical values
for the symmetric Cu2O2 core vibration.4a,45 Thus, on the basis
of the available spectroscopic evidence, we propose that argon
purging results in the formation of [(Me2LiPr,SXCu)2(µ-O)2].
The free energy change for the reaction of Me2LiPr,SMeCu with
dioxygen to form the singlet side-on Me2LiPr,SMeCuO2 is -20.5
kcal/mol at the experimental conditions of THF solvent and -80
°C and assuming standard 1 M concentrations. When basis set
superposition error (BSSE) is accounted for via counterpoise
calculations, ∆G increases by 5.5 kcal/mol to -15.0 kcal/mol.
The oxygenation reaction is thus predicted to be exergonic. At
the initial experimental reactant concentrations (0.2-10 mM),
the reaction proceeds to virtual completion; at the O2 binding
equilibrium, the amount of free Cu(I) complex relative to
Me2LiPr,SXCuO2 is predicted to be extremely small (0.03-0.23
ppm).
Theoretical calculations corroborate generation of [(Me2LiPr,SMe
-
Cu)2(µ-O)2] rather than its µ-η2:η2-peroxo isomer and provide
structural and energetic insights. Using a slightly truncated
model system in which the isopropyl groups were changed to
hydrogen atoms for computational expediency, calculations were
performed with the BLYP46 density functional using both
restricted and unrestricted methodologies. Singlet geometries
for both [(Me2LH,SMeCu)2(µ-O)2] and [(Me2LH,SMeCu)2(µ-η2:η2-
O2)] were optimized using the DZP basis and final energies
were determined using the TZP basis47 (see computational
Overall, the side-on theoretical structure for Me2LiPr,SMeCuO2
bears much similarity to the analogous O2 adduct 2a.19a-c
Coordination of dioxygen to Cu is nearly symmetric in both
systems, which may be expected considering the Cu ligation is
(42) Kinsinger, C. R.; Gherman, B. F.; Gagliardi, L.; Cramer, C. J. J. Biol.
Inorg. Chem. 2005, 10, 778-789.
(43) Schatz, M.; Raab, V.; Foxon, S. P.; Brehm, G.; Schneider, S.; Reiher, M.;
Holthausen, M. C.; Sundermeyer, J.; Schindler, S. Angew. Chem., Int. Ed.
2004, 43, 4360.
(44) Occupation numbers of 1.00 and 1.00 correspond to a pure Cu(II)-superoxo
mesomer, while 2.00 and 0.00 correspond to a pure Cu(III)-peroxo
mesomer. Occupation numbers between these two extremes provide a
quantitative measure of the point at which structures lie along the continuum
between these mesomers.
(45) (a) Mahapatra, S.; Halfen, J. A.; Wilkinson, E. C.; Pan, G.; Wang, X.;
Young, V. G., Jr.; Cramer, C. J.; Que, L., Jr.; Tolman, W. B. J. Am. Chem.
Soc. 1996, 118, 11555. (b) Henson, M. J.; Mukherjee, P.; Root, D. E.;
Stack, T. D. P.; Solomon, E. I. J. Am. Chem. Soc. 1999, 121, 10332.
(46) (a) Johnson, B. G.; Gill, P. M. W.; Pople, J. A. J. Chem. Phys. 1993, 98,
5612. (b) Becke, A. D. J. Chem. Phys. 1993, 98, 1372. (c) Lee, C. T.;
Yang, W. T.; Parr, R. G. Phys. ReV. B 1988, 37, 785.
(47) Siegbahn, P. E. M. J. Biol. Inorg. Chem. 2003, 8, 577.
9
3452 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

Effects of Thioether Substituents on O2 Reactivity
A R T I C L E S
Scheme 2
methods section). Solvation energies were calculated as well,
but vibrational frequency calculations proved prohibitively
expensive due to the ∼90-atom model size. Unrestricted
calculations on both the bis(µ-oxo) and the µ-η2:η2-peroxo
isomers converged to the restricted solution. The electronic
energy including solvation at -80 °C in THF (Esolv) was 9.3
kcal/mol lower for the bis(µ-oxo)dicopper(III) geometry (Figure
9b).48 This energy difference changes to 8.0 kcal/mol in the
gas phase, indicating that the bis(µ-oxo) geometry is better
solvated by 1.3 kcal/mol. The effect is less than was seen in
comparable calculations on {[(NH3)3Cu]2(µ-O)2}2+ and {[(NH3)3-
Cu]2(µ-η2:η2-O2)}2+ 49
, likely due to the steric bulk of the methyl
and phenyl groups partially screening the larger core charges
in the bis(µ-oxo) versus peroxo isomers. The geometry for the
triplet state of the [(Me2LH,SMeCu)2(µ-η2:η2-O2)] peroxo isomer
has a butterflied core, in contrast to the planar core of the singlet
state (Figure S16), and was computed to be 5.3 kcal/mol higher
in energy than the corresponding singlet and 14.6 kcal/mol less
stable than the bis(µ-oxo) form.
The optimized [(Me2LH,SMeCu)2(µ-O)2] structure shows no
copper-sulfur interactions, with the interatomic Cu-S distances
of 4.84 Å and the Cu centers having distorted square planar
the energy of reaction, which was then determined to be -20.8
kcal/mol at 193 K in THF (assuming standard state concentra-
tions of reactants). If the ∆S of this bimolecular reaction is
approximated to be on the order of -40 cal/mol‚K (e.g., on the
basis of comparison with computed ∆S of the oxygenation
reaction),50 the free energy of reaction is estimated to be -13
kcal/mol. The reaction to form [(Me2LH,SMeCu)2(µ-O)2] is thus
thermodynamically favorable, consistent with the experimental
results.
coordination geometries. Orientations of the two (Me2LH,SMe -
)
ligands were explored in which the two thioether appendages
were either anti or syn relative to the Cu2O2 plane, with the
latter leading to structures 1-2 kcal/mol lower in energy. The
small energy difference is unsurprising given the lack of Cu-S
bonding and the large distance (∼4.3 Å) between the thioether
appendages even when they are in the syn configuration.
To determine the energy of formation of [(Me2LH,SMeCu)2-
(µ-O)2] from Me2LH,SMeCuO2 and Me2LH,SMeCu, geometry
optimization followed by single-point energy calculations for
the 1:1 adduct and Cu(I) complex were carried out at the BLYP/
DZP and BLYP/TZP levels of theory, respectively. No CASPT2
To rationalize the experimentally observed formation of
[(Me2LiPr,SXCu)2(µ-O)2] from Me2LiPr,SXCuO2, we propose that
(i) argon purging promotes O2 loss from Me2LiPr,SXCuO2 to yield
a Cu(I) species, which (ii) is trapped by unreacted Me2LiPr,SX
-
CuO2 (Scheme 2). Both the absence of an observable amount
of bis(µ-oxo)dicopper complex generated during the oxygenation
of the Cu(I) starting material (performed with an excess of O2)
correction was made to the energy computed for Me2LH,SMe
-
and the need for forceful purging of solutions of Me2LiPr,SX
-
CuO2. Rather, it is presumed that the error in this energy is
approximately equal to the error in the BLYP energy for the
bis(µ-oxo) energy; that is, that BLYP improperly destabilizes
both to the same degree. This error cancels out in computing
CuO2 to induce bis(µ-oxo)dicopper complex formation suggests
that there is an O2 binding equilibrium characterized by very
slow dissociation of O2 (koff) at -80 °C and a relatively large
equilibrium constant (Keq). This conclusion is supported by the
magnitude of the computed free energy of oxygenation (-15.0
kcal/mol) for Me2LiPr,SMeCu. According to this model, rapid
purging is required so that the dissociated O2 is removed from
solution faster than it can be trapped by the generated Cu(I)
species to reform Me2LiPr,SXCuO2. Once the O2 is removed, the
(48) Reliable computation of the energy difference between structures with bis-
(µ-oxo)dicopper(III) and (µ-η2:η2-peroxo)dicopper(II) cores has proven to
be a difficult task. B3LYP and CASPT2 calculations have given conflicting
results for the relative energies in model systems with three ammonia ligands
per copper center.48a Delicate treatment of nondynamic electron correlation
in the two isomers has been shown to be critical.48a Multireference
configuration interaction (MRCI) methods have proved reliable, but are
applicable only to the very smallest of models.48b A thorough comparison
of the bis(µ-oxo) versus peroxo energy difference predicted by numerous
hybrid and pure density functionals as compared to MRCI, completely
renormalized coupled-cluster (CR-CC), and experimental results demon-
strated that pure density functionals (and in particular BLYP) were
considerably more accurate than their hybrid counterparts.48c This is largely
due to nondynamic correlation making a larger contribution to the energy
of the bis(µ-oxo)dicopper(III) core than to the (µ-η2:η2-peroxo)dicopper-
(II) core.48a Hybrid functionals, to the extent that they contain exact
exchange, suppress the nondynamic correlation nonspecifically incorporated
through the exchange functional, which detrimentally raises the relative
energy of the bis(µ-oxo) form. Consequently, we applied the pure functional
BLYP to the [(Me2LH,SMeCu)2(µ-O)2] and [(Me2LH,SMeCu)2(µ-η2:η2-O2)]
structures here. If B3LYP is utilized instead, Esolv is computed to be 3.5
kcal/mol higher for the bis(µ-oxo) than the peroxo isomer, an error versus
BLYP of 12.8 kcal/mol. This is consistent with the predictions from refs
48b and c that 5-7 kcal/mol of error should be expected per 10% Hartree-
Fock (HF) exchange present in the hybrid functional (B3LYP contains 20%
HF exchange). (a) Flock, M.; Pierloot, K. J. Phys. Chem. A 1999, 103, 95.
(b) Rode, M. F.; Werner, H.-J. Theor. Chem. Acc. 2005, 114, 309. (c)
Cramer, C. J.; Wloch, M.; Piecuch, P.; Puzzarini, C.; Gagliardi, L. J. Phys.
Chem. A 2006, 110, 1991.
Cu(I) species reacts irreversibly with the remaining Me2LiPr,SX
-
CuO2 to yield the bis(µ-oxo)dicopper intermediate. It is also
possible that the vigorous bubbling slightly warms the solution,
allowing for faster dissociation (koff) and/or reaction to form
the bis(µ-oxo)dicopper product.
In contrast, formation of a bis(µ-oxo)dicopper complex is not
observed under any conditions for the systems ligated by
(R2LiPr2)-.19 Multiple possible effects of the thioether substituent
(50) ∆S for the dimerization reaction is estimated as follows. The assumption
is first made that ∆Srot and ∆Svib are equal for the oxygenation and
dimerization reactions. The translational entropy for dioxygen, Me2LiPr,SMe
-
Cu, Me2LiPr,SMeCuO2, and [(Me2LiPr,SMeCu)2(µ-O)2] can be computed from
statistical mechanics, leading to ∆Strans ) -36.1 eu for the oxygenation
reaction and ∆Strans ) -41.6 eu for the dimerization reaction. The total
∆S for the oxygenation reaction (computed on the basis of vibrational
frequency calculations for all species in this reaction) is -34.6 eu. The
total ∆S for the dimerization reaction is then estimated to be -34.6 eu +
∆∆Strans ) -40 eu.
(49) Cramer, C. J.; Smith, B. A.; Tolman, W. B. J. Am. Chem. Soc. 1996, 118,
11283.
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3453

A R T I C L E S
Aboelella et al.
in (Me2LiPr,SX -
)
may be envisioned to underly these key
to model the N2S(thioether) ligand set of the postulated catalytic
“CuM” site of DâM and PHM. Copper(I) and (II) complexes of
these ligands have been prepared and characterized. Intramo-
lecular thioether coordination occurs in the monomeric Cu(II)
compounds. In the case of one Cu(I) complex, X-ray crystal-
lography indicates that a multinuclear structure is adopted in
the solid state wherein the thioether group of a ligand bound to
one copper ion binds to an adjacent metal center. Variable-
temperature 1H NMR studies of the Cu(I) compounds indicate
complex behavior in solution, which we attribute to equilibria
among species of varying nuclearity. Theoretical calculations
support the notion of thioether coordination in mononuclear Cu-
(I) species that may be present in solution. Low-temperature
oxygenation of solutions of the Cu(I) complexes generates stable
1:1 Cu/O2 adducts, which on the basis of UV-vis and resonance
Raman spectroscopic data and DFT calculations adopt side-on
“η2” structures with negligible Cu-thioether bonding and
significant peroxo-Cu(III) character similar to previously
reported analogues (2a and 2b)19 that lack the thioether group.
In contrast to 2a and 2b, however, purging the solutions of the
thioether-containing adducts with argon results in conversion
to bis(µ-oxo)dicopper(III) species, identified as such by spec-
troscopy and theory. Loss of O2 from the 1:1 Cu/O2 adduct
followed by rapid trapping of the product Cu(I) complex by
remaining adduct rationalizes the formation of the bis(µ-oxo)-
dicopper(III) complex. Thus, while the structure of the 1:1 Cu/
O2 adduct is not perturbed by the thioether substituent, the
equilibrium constant for O2 binding is decreased and bis(µ-oxo)
complex formation is enabled when the thioether group is
present.
differences in Cu/O2 chemistry. By coordinating to the Cu(I)
complex (a possibility supported by NMR, X-ray crystal-
lographic, and DFT results, see above), the thioether may inhibit
O2 binding (decrease kon), faciliate O2 dissociation (increase koff),
or both. Any of these effects would result in a smaller Keq as
compared to the system supported by (R2LiPr2)-, for which O2
binding is effectively irreversible at -80 °C. The reduced steric
demand of the thioether arm in (Me2LiPr,SX -
isopropyl substituent it replaces in (R2LiPr2 -
)
relative to the
)
is also probably
important, for such a reduction in size is necessary to access
the rather compact bis(µ-oxo)dicopper core. Indeed, it is known
that Cu(I) complexes of â-diketiminates that are less sterically
hindered than (R2LiPr2 -
fail to yield observable 1:1 Cu/O2
)
adducts and instead form bis(µ-oxo)dicopper species upon low-
temperature oxygenation.22 It is thus unusual to be able to
observe both the 1:1 Cu/O2 adduct and the bis(µ-oxo)dicopper
complex as stable intermediates with a single supporting ligand
system, further attesting to the novel properties of (Me2LiPr,SX)-.
(b) Reaction with PPh3. The addition of 1 equiv of PPh3 to
a solution of Me2LiPr,SXCuO2 that had been deoxygenated (by
slow argon purge, to avoid bis(µ-oxo)dicopper complex forma-
tion) resulted in the gradual decay of the spectral features
associated with the 1:1 Cu/O2 adduct, with an approximate time
to completion of 45 min for X ) Me and 150 min for X ) Ph
as judged by UV-vis spectroscopy (THF, -80 °C, 0.5 mM).
Characterization by 1H and 31P NMR spectroscopy of the
products resulting from warming of the reaction solutions to
room temperature indicated the formation of Me2LiPr,SXCu(PPh3)
(Scheme 1). Support for this assignment was obtained by
comparison of the data to that acquired for an independently
synthesized sample of Me2LiPr,SMeCu(PPh3), which was structur-
ally defined by X-ray crystallography (see above, Figure 4b).
In the case of X ) Me, the 31P NMR data also showed a small
amount of OPPh3 (∼14% by integration), but no oxidized
phosphine was observed in the case of X ) Ph.
The results reported herein provide precedence for a similar
influence of the methionine ligand on the kinetics and/or
thermodynamics of O2 binding to the CuM site in DâM and
PHM. Thus, the synthetic modeling work supports the notion11,12
that the methionine ligand may disfavor O2 binding, perhaps to
prevent leakage of oxidizing equivalents and/or to control the
timing of electron-transfer events. Recent theoretical calculations
suggest that the methionine may also induce other effects,
including preferential stabilization of an end-on geometry for a
Cu/O2 adduct in which the dioxygen moiety is less reduced than
in the well-characterized synthetic side-on systems.14 Testing
of these notions through experiment remains an important goal
for future research.
The finding that PPh3 displaces O2 from Me2LiPr,SXCuO2 to
yield a Cu(I) phosphine adduct parallels the results of the
analogous reaction with Me2LiPr2CuO2 (2a, R ) Me), although
the rates are significantly different.36 At -80 °C, the parent
complex Me2LiPr2CuO2 is unreactive with PPh3, and only yields
the phosphine adduct upon warming, whereas conversion of the
thioether-substituted system occurs at -80 °C. An associative
mechanism was determined previously on the basis of kinetic
data for the reaction of Me2LiPr2CuO2 with the less hindered
reagent PMePh2.36 Such an associative pathway may underly
the faster rate of the reaction of PPh3 with the thioether-
substituted system, which is less sterically encumbered. Alter-
natively, thioether-induced pre-equilibrium loss of O2 from
Me2LiPr,SXCuO2 (as proposed to occur upon argon purging, as
described above) could provide Me2LiPr,SXCu, which would then
be trapped by PPh3. The difference in rate between the ligands
(X ) Me > X ) Ph) reflects their steric profiles, which would
be expected to be manifested similarly in the associative and
pre-equilibrium dissociative paths. Distinguishing between these
possibilities will require extensive kinetic studies that have yet
to be performed.
Experimental Section
General Considerations. All reagents were obtained from com-
mercial sources and used without further purification, unless otherwise
stated. The solvents THF, toluene, pentane, and Et2O were dried over
Na/benzophenone and distilled under nitrogen or passed through solvent
purification columns (Glass Contour, Laguna, CA). All metal complexes
were prepared and stored in a Vacuum Atmospheres inert atmosphere
glovebox under a dry nitrogen atmosphere or were manipulated using
standard inert atmosphere vacuum and Schlenk techniques. The copper
reagents (Me3SiCH2Cu)432 and CuCl2‚0.8THF51 were prepared according
to literature procedures. 6-iPr-2-Methylthiomethylaniline25,26,52 and
2-(2,6-diisopropylphenylimido)-2-pentene-4-one27 were prepared ac-
cording to literature procedures. Labeled dioxygen was purchased from
Cambridge Isotopes, Inc. or Icon Isotopes, Inc.
Conclusion
(51) So, J.-H.; Boudjouk, P. Inorg. Chem. 1990, 29, 1592.
(52) Note that this reaction is performed at -80 °C, not at 80 °C as stated in
ref 25.
In summary, we have prepared two new ligands comprised
of bidentate â-diketiminates with thioether substituents designed
9
3454 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

Effects of Thioether Substituents on O2 Reactivity
A R T I C L E S
Physical Methods. NMR spectra were recorded on either Varian
an orange solid, which was further recrystallized from 75 mL of boiling
EtOH. The volume was reduced to approximately 25 mL, and the
solution was cooled to room temperature before placing in a -25 °C
freezer. The resulting off-white crystals were isolated via vacuum
filtration, washed with a minimal amount of cold EtOH (-80 °C), and
dried in vacuo (2.74 g, 30%). Note: Despite repeated attempts at
recrystallization, the crystalline product is a mixture of the desired
VI-300 or VXR-300 spectrometers. Chemical shifts (δ) for 1H and 13
C
NMR spectra are reported versus tetramethylsilane and were referenced
to residual protium in the deuterated solvent. 31P NMR spectra are
referenced externally to 85% H3PO4. UV-vis spectra were recorded
on an HP8453 (190-1100 nm) diode array spectrophotometer. Low-
temperature spectra were acquired through the use of a Unisoko low-
temperature UV-vis cell holder. When necessary, UV-vis spectra were
corrected for drifting baselines due to minimal frosting of the UV cells
caused by the low-temperature device. This was achieved by subtracting
the average of a region with no absorbance (i.e., baseline, typically
950-1000 nm) from the entire spectrum. X-band EPR spectra were
recorded on a Bruker E-500 spectrometer, with an Oxford Instruments
EPR-10 liquid helium cryostat (4-20 K, 9.61 GHz). Quantitation of
EPR signal intensity was accomplished by comparing the double
integration of the derivative spectrum to that of H(Me2LiPr2)CuCl28 in
1:1 toluene/CH2Cl2. Resonance Raman spectra were collected on an
Acton AM-506 spectrometer using a Princeton Instruments liquid N2
cooled (LN1100-PB) CCD detector and ST-1385 controller interfaced
with Winspec software. A Spectra-Physics BeamLok 2060-KR-V
Krypton ion laser was used to excite at 406.7 or 457.9 nm. The spectra
were obtained at -196 °C using a backscattering geometry; samples
were frozen in a copper cup attached to a liquid nitrogen cooled
coldfinger. Raman shifts were either externally referenced to liquid
indene or internally referenced to solvent. Baseline corrections (poly-
nomial fits) were carried out using Grams/32 Spectral Notebase Version
4.04 (Galactic). Elemental analyses were performed by Atlantic
Microlab, Inc.
product, Me2
LiPr,SMeH, and the byproducts, Me2LiPr2H and Me2LSMe2H.
Performing the reaction under nitrogen, as described above, optimizes
the yield of product relative to byproducts to an approximate ratio of
6:3:1 by NMR spectroscopy. 1H NMR (300 MHz, C6D6): δ 12.41 (s,
1H), 7.23-7.02 (m, 6H), 4.90 (s, 1H), 3.68 (d, J ) 13.2 Hz, 1H), 3.58
(d, J ) 13.2 Hz, 1H), 3.42-3.18 (m, 3H), 1.80 (s, 3H), 1.75 (s, 3H),
1.62 (s, 3H), 1.21-1.10 (m, 18H) ppm. 13C{1H} NMR (75 MHz,
C6D6): δ 164.2, 159.4, 144.5, 144.3, 141.6, 138.5, 130.4, 127.2, 126.3,
124.7, 124.0, 123.4, 123.3, 123.2, 93.8, 35.5, 28.5, 28.4, 28.0, 24.7,
24.4, 24.3, 23.4, 23.3, 23.1, 21.7, 20.6, 15.8 ppm. HRESIMS: calcd
for C28H41N2S ([M + H]+), 437.2985. Found: m/z ) 437.2987.
Me2LiPr,SPhH. Under nitrogen, a 250 mL two-neck flask was
equipped with a Dean Stark apparatus, and 2-(2,6-diisopropylphenyl-
imido)-2-pentene-4-one (5.54 g, 0.021 mol) and 6-isopropyl-2-phen-
yllthiomethylaniline (5.45 g, 0.021 mol) were dissolved in dry toluene
(150 mL). Methanesulfonic acid (1.4 mL, 0.022 mol) was added, and
the reaction mixture was refluxed under nitrogen overnight. Ap-
proximately 100 mL of toluene was removed by distillation before the
remainder of the solvent was removed under reduced pressure.
Approximately 100 mL of CH2Cl2 and 100 mL of saturated Na2CO3
were added to the resulting brown oil and stirred for 5 min. The layers
were separated, and the aqueous layer was washed with CH2Cl2 (2 ×
50 mL). The organics were combined and washed with 100 mL of
saturated NaCl solution, then dried over anhydrous MgSO4 and filtered.
The solvent was removed from the filtrate under reduced pressure to
yield a brown solid. MeOH was added (20 mL), and the mixture was
stirred vigorously to yield a tan precipitate, which was isolated via
vacuum filtration. The solid was recrystallized from 100 mL of boiling
EtOH, allowed to cool to room temperature, and then stored at -4 °C.
The resulting crystals were isolated and washed with cold EtOH (-80
°C) (3.50 g, 33%). 1H NMR (300 MHz, C6D6): δ 12.46 (s, 1H), 7.40-
6.90 (m, 11H), 4.90 (s, 1H), 4.21 (d, J ) 12.4 Hz, 1H), 4.11 (d, J )
12.4 Hz, 1H), 3.35-3.18 (m, 3H), 1.81 (s, 3H), 1.61 (s, 3H), 1.21-
1.14 (m, 9H), 1.12 (d, J ) 6.9 Hz, 6H), 1.06 (d, J ) 6.9 Hz, 3H) ppm.
13C{1H} NMR (75 MHz, C6D6): δ 165.0, 158.9, 145.1, 144.7, 144.6,
143.2, 141.2, 137.9, 137.7, 129.9, 129.1, 128.9, 127.4, 126.5, 126.2,
125.1, 124.0, 123.4, 123.3, 93.9, 36.3, 28.5, 28.0, 24.7, 24.6, 24.3, 23.3,
23.2, 23.0, 21.9, 20.5 ppm. Anal. Calcd for C33H42N2S: C, 79.47; H,
8.49; N, 5.62. Found: C, 79.31; H, 8.47; N, 5.59.
6-Isopropyl-2-phenylthiomethylaniline. This compound was pre-
pared in a manner analogous to published procedures for 6-isopropyl-
2-methylthiomethylaniline and related anilines.25,26 Under nitrogen, dry
CH2Cl2 (125 mL) was cooled to -80 °C in a 250 mL two-neck flask.
To this were added 2-isopropylaniline (12 mL, 0.083 mol) and
thioanisole (11 mL, 0.094 mol) while maintaining a temperature of
-80 °C. N-Chlorosuccinimide (12.67 g, 0.095 mol) was added in
portions over 30 min. The mixture was stirred and warmed to room
temperature to yield a dark orange solution. Triethylamine (14.5 mL,
0.10 mol) was added, which caused the solution to turn very dark purple,
and the mixture was then refluxed for 1 day. The reaction mixture was
then cooled to room temperature and extracted with 10% w/v NaOH
(2 × 250 mL). The combined organic layers were dried over Na2SO4,
filtered, and the solvent was removed under reduced pressure to yield
a dark red oil, which was purified by silica gel column chromatography
1
(90:10 hexanes/ethyl acetate). Yield ) 6.12 g (29%). H NMR (300
MHz, CDCl3): δ 7.38-7.20 (m, 5H), 7.10 (dd, J ) 1.5, 7.8 Hz, 1H),
6.91 (dd, J ) 1.5, 7.5 Hz, 1H), 6.70 (t, J ) 7.8 Hz, 1H), 4.14 (s, 2H),
4.11 (br. s, 2H), 2.94 (heptet, J ) 6.9 Hz, 1H), 1.27 (d, J ) 6.9 Hz,
6H). 13C{1H} NMR (75 MHz, CDCl3): δ 142.5, 136.3, 133.3, 130.3,
129.1, 128.6, 126.7, 125.2, 120.8, 118.6, 37.5, 27.9, 22.6. Anal. Calcd
for C15H17NS: C, 74.66; H, 7.44; N, 5.44. Found: C, 74.20; H, 7.49;
N, 5.38.
Me2LiPr,SMeH. Under nitrogen in a 250 mL two-neck flask equipped
with a Dean Stark apparatus, 2-(2,6-diisopropylphenylimido)-2-pentene-
4-one (5.49 g, 0.021 mol) and 6-isopropyl-2-methylthiomethylaniline
(4.37, 0.022 mol) were dissolved in dry toluene (150 mL). Methane-
sulfonic acid (1.4 mL, 0.022 mol) was added, and the reaction mixture
was refluxed under nitrogen overnight. Approximately 100 mL of
toluene was removed by distillation before the remainder of the solvent
was removed under reduced pressure. Approximately 100 mL of CH2-
Cl2 and 100 mL of saturated Na2CO3 were added to the resulting brown
oil and stirred for 5 min. The layers were separated, and the aqueous
layer was washed with CH2Cl2 (3 × 50 mL). The organics were
combined and washed with 100 mL of saturated NaCl solution, then
dried over anhydrous Na2SO4 and filtered. The solvent was removed
from the filtrate under reduced pressure to yield an orange oil. EtOH
was added (10 mL) and then removed under reduced pressure to yield
Me2LiPr,SMeLi. A 2.5 M solution of nBuLi in hexane (0.58 mL, 1.45
mmol) was added to a stirring solution of the ∼ 6:3:1 mixture of
Me2LiPr,SMeH and the byproducts Me2LiPr2H and Me2LSMe2H (0.630 g
of the mixture, which corresponds to ∼0.380 g, ∼0.87 mmol of
Me2LiPr,SMeH) in 5 mL of pentane. The desired product precipitated
out of solution as a white solid, and the reaction mixture was allowed
to stir for 1 h. The solid was collected via vacuum filtration and washed
1
with cold pentane (0.369 g, ∼96% based on Me2LiPr,SMeH). H NMR
(300 MHz, C6D6): δ 7.26-7.12 (m, 4H), 6.92 (t, 1H), 6.72, (dd, J )
7.5, 1.5 Hz, 1H), 4.92 (s, 1H), 3.50-3.39 (m, 4H), 2.91 (d, J ) 12.3
Hz, 1H), 1.89 (s, 3H), 1.80 (s, 3H), 1.31-1.19 (m, 21H) ppm. 13C-
{1H} NMR (75 MHz, C6D6): 183.0, 165.3, 161.8, 150.8, 149.5, 142.2,
141.5, 141.2, 129.2, 126.3, 124.1, 123.8, 122.1, 93.5, 37.8, 28.5, 28.3,
28.1, 25.1, 25.0, 24.9, 24.8, 24.1, 23.7, 23.3, 23.0, 14.5 ppm.
Me2LiPr,SMeCu. A solution of Me2LiPr,SMeLi (249 mg, 0.56 mmol) in
4 mL of THF was added to a slurry of CuCl (56.0 mg, 0.57 mmol) in
4 mL of THF. The solution immediately became bright yellow and
was stirred for 1 h. The solvent was removed under reduced pressure,
and the residue was extracted with ∼15 mL of pentane. The extract
was filtered through Celite, and the solvent was then removed under
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3455

A R T I C L E S
Aboelella et al.
reduced pressure. The resulting yellow residue was stirred in pentane
for 5 min. A yellow precipitate formed, which was isolated via vacuum
filtration, washed with 5 mL of cold (-20 °C) pentane, and dried in
(ꢀ, M-1 cm-1)]: 275 (9200), 340 (15 900), 487 (1800), 598 (670), 875
(500). HRESIMS: calcd for C33H41N2SclCu, 595.1970 (M+). Found:
m/z ) 595.1983. HREIMS: calcd for C33H40N2SCl2Cu, 629.1585 (M+).
Found: m/z ) 629.1627.
1
vacuo (214 mg, 76%). H NMR (300 MHz, C6D6): δ 7.27-7.15 (m,
Me2LiPr,SMeCu(PPh3). A solution of PPh3 (22.3 mg, 0.085 mmol)
4H), 6.88 (t, J ) 7.5 Hz, 1H), 6.77 (d, J ) 7.5 Hz, 1H), 4.88 (s, 1H),
3.66 (heptet, J ) 6.6 Hz, 1H), 3.51-3.43 (m, 2H), 3.34 (heptet, J )
6.6 Hz, 1H), 3.15 (d, J ) 11.4 Hz, 1H), 1.89 (s, 3H), 1.77 (s, 3H),
1.40 (d, J ) 6.6 Hz, 3H), 1.31-1.27 (m, 12H), 1.18 (s, 3H), 1.09 (d,
J ) 6.9 Hz, 3H) ppm. UV-vis (THF) [λmax, nm (ꢀ, M-1 cm-1)]: (27
°C) 253 (sh, 16 700), 280 (sh, 11 200), 382 (19 500); (-80 °C) 255
(sh, 16 700), 280 (sh, 13 600), 357 (18 200), 382 (16 400). HRES-
IMS: calcd for C28H40N2Scu, 499.2203 ([M + H]+). Found: m/z )
499.2230. Anal. Calcd for C28H39N2SCu: C, 67.36; H, 7.87; N, 5.61.
Found: C, 66.99; H, 7.95; N, 5.30
in 2 mL of THF was added to a bright yellow suspension of Me2LiPr,SMe
-
Cu (42.6 mg, 0.085 mmol) in 4 mL of THF. The solution immediately
bleached and became cloudy. After being stirred for 1 h, the mixture
became clear and pale yellow. The solvent was then removed under
reduced pressure to yield a sticky pale yellow residue. Repeated cycles
of dissolution in pentane (∼2 mL) and subsequent evaporation under
reduced pressure eventually yielded an off-white solid (2-3 repetitions)
(30.0 mg, 46%). X-ray quality crystals were obtained by slow
evaporation of a concentrated Et2O solution at -20 °C. 1H NMR (C6D6,
300 MHz): δ 7.26-6.87 (m, 21H), 5.16 (s, 1H), 3.91 (d, J ) 13.5 Hz,
1H), 3.70-3.47 (m, 3H), 3.18 (d, J ) 13.5 Hz, 1H), 1.97 (s, 3H), 1.87
(s, 3H), 1.73 (s, 3H), 1.28-1.22 (m, 9H), 0.98 (d, J ) 6.9 Hz, 3H),
0.89-0.84 (m, 6H). ppm. 31P{1H} NMR (C6D6, 121.5 MHz): δ 3.79
ppm. Anal. Calcd for C46H54CuN2SP: C, 72.55; H, 7.15; N, 3.68.
Found: C, 72.79; H, 7.07, N, 3.67.
Me2LiPr,SPhCu. A solution of Me2LiPr,SPhH (0.175 g, 0.35 mmol) in
5 mL of THF was added to solid (Me3SiCH2Cu)4 (53.4 mg, 0.088
mmol) in a foil-wrapped vial. (Note: (Me3SiCH2Cu)4 is light-sensitive;
thus care must be taken to exclude excessive light.) The reaction mixture
was stirred for 4.5 h and then filtered through Celite. The yellow filtrate
was placed in a -20 °C freezer to precipitate the product as an off-
white solid. The precipitate was collected via vacuum filtration, washed
X-ray Crystallography. General Procedure. A crystal of appropri-
ate size was placed on the tip of a 0.1 mm diameter glass capillary and
mounted on either a Siemens or a Bruker SMART Platfrom CCD
diffractometer for data collection at 173(2) K. The data collection was
carried out using Mo KR radiation (graphite monochromator) with an
appropriate frame time for the size and quality of the crystal. A
randomly oriented region of reciprocal space was surveyed to the extent
of one sphere and to a resolution of either 0.84 or 0.77 Å. At least
three major sets of frames were collected with 0.30° steps in ω at
different φ settings and a detector position of -28° in 2θ. The intensity
data were corrected for absorption and decay (SADABS).54 Integration
of the actual data was performed using SAINT.55 The structure was
solved using Sir9756 (unless otherwise stated) and refined using
SHELXL-97 (Sheldrick, 1997).57 A direct methods solution was
calculated, which provided most non-hydrogen atoms from the E-map.
The remaining non-hydrogen atoms were located using full-matrix least
squares/difference Fourier cycles. All non-hydrogen atoms were refined
with anisotropic displacement parameters, unless stated otherwise. All
hydrogen atoms were placed in ideal positions and refined as riding
atoms with relative isotropic displacement parameters, unless stated
otherwise. Further crystal and collection details are provided in the
Supporting Information (CIF).
Me2LiPr,SPhH. X-ray quality crystals were grown from a concentrated
EtOH solution. The N-H hydrogen was found by the E-map and
refined accordingly. All other hydrogen atoms were placed in ideal
positions and refined as riding atoms. Electron density corresponding
to partial occupancy of hydrogen was found at both ligand nitrogen
atoms, N1 and N2, indicating the hydrogen atom could reside at either
nitrogen. In addition, each hydrogen electron density is within hydrogen-
bonding distance of the other nitrogen. The hydrogen was thus modeled
as disordered over two positions, H1 and H2, and refined to occupancies
of 30% and 60%, respectively. The final full matrix least squares
refinement converged to R1 ) 0.0561 and wR2 ) 0.1289 (F2, all data).
[Me2LiPr,SMeCu]4. X-ray quality crystals were obtained from vapor
diffusion of diethyl ether into a THF solution at -20 °C. Data collection
was carried out on a Bruker Kappa SMART 6000 system at 100(1) K.
The data collection was carried out using 0.4860 Å radiation (double-
diamond monochromator) with a frame time of 1 s and a detector
distance of 5.0 cm.58 A randomly oriented region of reciprocal space
1
with ∼2 mL of cold pentane, and dried in vacuo (0.129 g, 65%). H
NMR (300 MHz, C6D6): δ 7.20-7.11 (m, 4H), 6.86 (d, J ) 7.2 Hz,
2H), 6.79-6.64 (m, 4H), 6.43 (d, J ) 6.9 Hz, 1H), 4.94 (s, 1H), 3.73-
3.46 (m, 4H), 3.38 (septet, J ) 6.6 Hz, 1H), 1.93 (s, 3H), 1.79 (s, 3H),
1.31-1.26 (m, 15H), 1.17 (d, J ) 6.6 Hz, 3H) ppm. UV-vis (THF)
[λmax, nm (ꢀ, M-1 cm-1)]: (27 °C) 242 (sh, 22 000), 282 (sh, 10 800),
380 (19 200); (-80 °C) 255 (sh, 15 600), 275 (sh, 13 300), 360 (16 300),
382 (15 200). HRESIMS: calcd for C33H42N2Scu, 561.2359 ([M +
H]+). Found: m/z ) 561.2345. Anal. Calcd for C33H41N2SCu: C, 70.61;
H, 7.36; N, 4.99. Found: C, 69.63; H, 7.48; N, 4.76.
Me2LiPr,SMeCuCl. A solution of Me2LiPr,SMeLi (169 mg, 0.38 mmol)
in 2 mL of THF was added to a slurry of CuCl2‚0.8THF (78.4 mg,
0.38 mmol) in 1 mL of THF. The solution turned dark brown/purple
immediately. The reaction mixture was stirred for 4 h, and then the
solvent was removed under reduced pressure. The resulting residue was
dissolved in ∼8 mL of toluene and filtered through Celite. The volume
of the filtrate was reduced to approximately 4 mL under reduced
pressure, and approximately 3 mL of pentane was added to the solution.
The mixture was then placed in a -20 °C freezer for 5-6 days to
produce dark purple/brown crystals (94.4 mg, ∼46%).53 X-ray quality
crystals were grown from a 2:1 toluene/pentane solution. Note: The
isolated single crystals contain a mixture of the desired product, as
well as a byproduct, with a chlorine in the central methine position of
the ligand backbone. UV-vis (CH2Cl2) [λmax, nm (ꢀ, M-1 cm-1)]: 279
(9000), 329 (16 700), 450 (1600), 577 (760), 850 (580). HRESIMS:
calcd for C28H40N2SclCu, 534.1891 ([M + H]+). Found: m/z )
534.1894. HREIMS: calcd for C28H38N2SCl2Cu, 567.1429 (M+).
Found: m/z ) 567.1411.
n
Me2LiPr,SPhCuCl. A 2.5 M solution of BuLi in hexanes (0.16 mL,
0.40 mmol) was added to Me2LiPr,SPhH (208 mg, 0.42 mmol) in ∼10
mL of pentane. The solution was stirred for 1 h. The solvent was then
removed under reduced pressure to leave an orange residue. The residue
was dissolved in ∼4 mL of THF and added to a slurry of CuCl2‚0.8THF
(76.7 mg, 0.40 mmol) and stirred for 5 h. The solution became deep
purple. The solvent was removed under reduced pressure, and the
resulting residue was dissolved in ∼4 mL of toluene. The solution was
filtered through Celite, and ∼4 mL of pentane was added and the
mixture placed in a -20 °C freezer for 5-6 days. The resulting X-ray
quality crystals were isolated and washed with pentane (112 mg,
∼47%).53 Note: The isolated single crystals contain a mixture of the
desired product, as well as a byproduct with a chlorine in the central
methine position of the ligand backbone. UV-vis (CH2Cl2) [λmax, nm
(54) An empirical correction for absorption anisotropy. Blessing, R. Acta
Crystallogr. 1995, A51, 33.
(55) SAINT V6.2; Bruker Analytical X-ray Systems: Madison, WI, 2001.
(56) Altomare, A.; Burla, M. C.; Cascarano, G.; Giacovazzo, C.; Guagliardi,
A.; Moliterni, G. G.; Polidori, G.; Spagna, R. J. Appl. Crystallogr. 1998,
32, 115.
(53) This yield assumes no chloride incorporation in the backbone, although it
is indicated by X-ray crystallography.
(57) SHELXTL V6.10; Bruker Analytical X-ray Systems: Madison, WI, 2000.
(58) Data were collected at APS ChemMatCARS 15-ID-C.
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3456 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006

Effects of Thioether Substituents on O2 Reactivity
A R T I C L E S
was surveyed to the extent of 2.0 hemispheres and to a resolution of
0.84 Å. Two sets of frames were collected with 0.30° steps in ω and
one complete rotation of φ. The structure was solved using Bruker
SHELXTL.57 The structure consists of a tetramer of copper complexes.
Only one-half of the tetramer is unique, with the other half generated
by symmetry through an inversion center. There is a large librational
motion of the isopropyl group (C42, C43, C44) about the C37-C42
bond, which causes disorder of the isopropyl group. This disorder was
modeled by splitting these atoms into two parts with fixed 50/50
occupancy. The final full matrix least squares refinement converged
to R1 ) 0.0483 and wR2 ) 0.1190 (F2, all data).
argon through the solution for ∼10 min. One equivalent of PPh3 (0.22
mL, 120 mM) dissolved in THF was introduced via syringe (0.22 mL),
and the solutions were stirred for 80 min at -80 °C. The color faded
to yellow (X ) Me) or orange (X ) Ph). Upon warming to room
temperature, further bleaching to pale yellow was observed. The solvent
was removed under reduced pressure, and the resulting residue was
dissolved in anaerobic and dry C6D6. 31P{1H} NMR (C6D6, 121.5 MHz)
X ) Me: δ 3.83 (Me2LiPr,SMeCu(PPh3), 86%), 25.48 (OPPh3, 14%)
ppm. X ) Ph: δ 3.94 ppm (Me2LiPr,SPhCu(PPh3)).
Computational Methods. (A) Density Functional Calculations.
Geometry optimizations were carried out with the Jaguar suite, version
5.0, of ab initio quantum chemistry programs.60 Because it has been
demonstrated to be successful in predicting ligand-Cu(I) and -Cu(II)
bond dissociation energies,61 density functional theory (DFT) with the
B3LYP functional46 was used for geometry optimizations. Calculations
were carried out at the restricted (RDFT) and unrestricted (UDFT) levels
for singlet and triplet cases, respectively, according to the prescription
identified in previous studies of 1:1 adducts of Cu(I) and dioxy-
gen.14,19c,d,20b The lacvp** effective core potential basis62 was used for
Cu, while the double-ú plus polarization (DZP) 6-31G** basis set was
used for all other atoms.
Me2LiPr,SMeCuCl. X-ray quality crystals were grown from a 2:1
toluene/pentane mixture at -20 °C. This structure displays a minor
compositional disorder in which the atom attached to C3 is either a
hydrogen, as expected, or a chlorine (90:10, H:Cl). There is no other
disorder in the main molecule. A toluene solvent molecule is present
in the crystal structure; however, it is highly disordered and attempts
to model it were unsuccessful. Thus, it was removed using the program
PLATON/SQUEEZE.59 A void volume of 858.3 Å3 (with 196 electrons)
out of a unit cell volume of 3378.1 Å, 25.4%, was found. The final
full matrix least squares refinement converged to R1 ) 0.0566 and
wR2 ) 0.1334 (F2, all data).
Vibrational frequencies were calculated analytically and served to
verify the B3LYP/DZP optimized geometries as minima. The calcula-
tions also enabled the determination of free energies by allowing for
zero-point, enthalpy, and entropy corrections to be made. To optimize
comparison of computed ν(O-O) values with those determined
experimentally,20 structures were reoptimized with B3LYP using the
polarized triple-ú (TZP) 6-311G** basis set on all atoms, except for
Cu, for which the lacv3p** basis set (a triple-ú basis compatible with
the effective core potential)62 was used. Frequencies at this level were
scaled by 0.97 prior to reporting.63 All vibrational frequency calculations
were performed with a truncated ligand system for the sake of
computational tractability: the three isopropyl groups are replaced with
hydrogen atoms, and the positions of these atoms are optimized while
holding the remainder of the structure fixed.
Me2LiPr,SPhCuCl. X-ray quality crystals were grown from a 1:1
toluene/pentane solution at -20 °C. This structure displays a compo-
sitional disorder in which the atom attached to C3 is either a hydrogen,
as expected, or a chlorine (53:47, H:Cl). There is no other disorder in
the main molecule. The toluene solvent molecule contains a few large
thermal ellipsoids. FLAT and DELU restraints were applied to the
toluene to improve the model. However, further attempts to model the
disorder did not lead to any improvement. The final full matrix least
squares refinement converged to R1 ) 0.0472 and wR2 ) 0.1424 (F2,
all data).
Me2LiPr,SMeCu(PPh3). X-ray quality crystals were obtained from
evaporation of a diethyl ether solution at -20 °C. The structure was
solved using SHELXS-9757 and refined using SHELXL-97 (Sheldrick,
1997).57 The final full matrix least squares refinement converged to
R1 ) 0.0503 and wR2 ) 0.1201 (F2, all data)
Single-point solvation energies for the optimized geometries were
calculated using the self-consistent reaction field method as imple-
mented in the Poisson-Boltzmann solver in Jaguar.64 The dielectric
constant ꢀ for THF, which is used as the solvent for the purpose of
comparison to experimental data, was taken to be 7.43 at 25 °C and
12.27 at -80 °C.65 Computed gas-phase free energies for all species
were converted from the 1 atm to the 1 M standard state by addition
of a factor of -RT*ln(A), where R is the universal gas constant and A
is the molar volume of an ideal gas at 1 atm and a given temperature
T.66 Molar equilibrium concentrations for reactants and products in
complexation reactions were computed from equilibrium constants
determined as Keq ) exp(-∆G/RT).
(B) Multireference Calculations. Accurately modeling the open-
shell singlet character of 1:1 adducts of Cu(I) and dioxygen, in particular
those with a significant degree of Cu(II)-superoxo character, neces-
sitates the use of methods beyond DFT. Although closed-shell singlet
and high-spin triplet Kohn-Sham wave functions can be expressed as
single Slater determinants, such open-shell singlet states are not a priori
UV-Visible Absorption Spectroscopy. Formation of Me2-
LiPr,SXCuO2. In a typical experiment, a 0.2-0.4 mM solution of
Me2LiPr,SXCu in THF, toluene, or CH2Cl2 was placed in a UV cell in
an inert atmosphere glovebox. The cuvette was sealed and brought out
of the glovebox and cooled to -80 °C. The solution was oxygenated
via bubbling excess dry O2 for approximately 10 min, although the
reaction is complete almost immediately.
Formation of [(Me2LiPr,SXCu)2(µ-O)2]. The 1:1 adduct, Me2LiPr,SX
-
CuO2, was prepared as described above (0.2-0.4 mM). Argon was
then vigorously bubbled through the solution at -80 °C to produce
the brown species, [(Me2LiPr,SXCu)2(µ-O)2].
Resonance Raman Spectroscopy. Samples were prepared via the
same protocols as described above for the UV-visible absorption
spectroscopy experiments, except the initial Cu(I) concentrations were
∼10 mM. Samples for 18O2-labeled resonance Raman experiments were
prepared via freezing a solution of Me2LiPr,SXCu in a 10-mL Schlenk
flask, evacuating the headspace, and vacuum transferring approximately
10 mL of 18O2 gas. The Schlenk flask was then warmed to -80 °C
(60) Jaguar 5.0; Schrodinger, LLC: Portland, OR, 2002.
(61) Ducere, J.-M.; Goursot, A.; Berthomieu, D. J. Phys. Chem. A 2005, 109,
400.
(62) (a) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270. (b) Wadt, W.
R.; Hay, P. J. J. Chem. Phys. 1985, 82, 284. (c) Hay, P. J.; Wadt, W. R.
J. Chem. Phys. 1985, 82, 299.
(63) Bauschlicher, C. W.; Partridge, H. J. Chem. Phys. 1995, 103, 1788.
(64) (a) Marten, B.; Kim, K.; Cortis, C.; Friesner, R. A.; Murphy, R. B.;
Ringnalda, M. N.; Sitkoff, D.; Honig, B. J. Phys. Chem. 1996, 100, 11775.
(b) Tannor, D. J.; Marten, B.; Murphy, R.; Friesner, R. A.; Sitkoff, D.;
Nicholls, A.; Ringnalda, M.; Goddard, W. A.; Honig, B. J. Am. Chem.
Soc. 1994, 116, 11875.
with vigorous stirring to produce the mononuclear adducts, Me2LiPr,SX
-
CuO2. The 18O2-labeled bis(µ-oxo) species, (Me2LiPr,SXCu)2(µ-O)2, was
prepared via bubbling argon vigorously through this solution.
Reactivity Studies of Me2LiPr,SXCuO2 with PPh3. A solution of
H(Me2LiPr,SX)Cu (ca. 2.6 mL, 10 mM)) in THF was placed in a 10 mL
Schlenk flask under anaerobic conditions, cooled to -80 °C, and
oxygenated by bubbling dry O2 to produce a dark green solution of
Me2LiPr,SXCuO2. The solutions were deoxygenated by bubbling dry
(65) (a) Carvajal, C.; Tolle, K. J.; Smid, J.; Szwarc, M. J. Am. Chem. Soc. 1965,
87, 5548. (b) Metz, D. J.; Glines, A. J. Phys. Chem. 1967, 71, 1158.
(66) Cramer, C. J. Essentials of Computational Chemistry. Theories and Models;
John Wiley & Sons, Ltd.: West Sussex, England, 2002.
(59) Spek, A. L. Acta Crystallogr. 1990, A46, C34. Spek, A. L. PLATON, A
Multipurpose Crystallographic Tool, Utrecht University, Utrecht, The
Netherlands, 2000.
9
J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006 3457

A R T I C L E S
Aboelella et al.
representable within the framework of Kohn-Sham DFT because they
formally can only be expressed by at least two determinants. The
multideterminantal nature of the 1:1 singlet adducts can be accounted
for using single-point multireference second-order perturbation theory
(CASPT2) calculations.67,68 These computations also yield accurate
singlet-triplet energy differences. The complete active space (CAS)
for the reference wave function contains 18 electrons and 12 orbitals
comprised from the Cu valence electrons/orbitals and the O2 σ2p, σ2p*,
π2p, and π2p* electrons/orbitals. Removal of orbitals with occupation
numbers greater than 1.999 led to a final (12,9) active space. All CAS
and CASPT2 calculations were carried out with the MOLCAS
program.69 A triple-ú quality 17-electron relativistic effective core
potential basis set was used for Cu,70 and a TZP atomic natural orbital
basis was used for S, O, N, and H(-N).71 To keep calculations tractable,
carbon was treated with the 3-21G basis72 and H(-C) with the STO-
3G basis.73 As an additional step to facilitate these intensive calculations,
a simplified version of the ligand system was used in which the
backbone methyl groups and 2,6-diisopropylphenyl flanking groups (but
retaining the thioether ligation to Cu) were transmuted to H atoms.
The positions of these capping hydrogen atoms were optimized at the
B3LYP/DZP level prior to CASPT2 calculations. The difference ∆ (eq
1) in the relative energies of the singlet and triplet states at the DFT
and CASPT2 levels was calculated for these small models. Assuming
the triplet state is well represented within the DFT single-determinantal
formalism, the relative energy difference between the triplet at the two
levels of theory is negligible. The quantity ∆ then becomes equal to
the relative energy difference of the singlet state at the DFT and
CASPT2 levels. By adding ∆ to the DFT energies computed for the
singlet states with the full model, final electronic energies, which then
include an accounting for the multideterminantal character of the
biradical singlet state, are obtained for the optimized structures with
the full (Me2LiPr,SMe - ligand. This procedure has been shown to yield
)
reliable energies for 1:1 Cu-O2 adducts supported by similar ligand
systems.19c,d
∆ ) (1A - 3A)CASPT2 - (1A - 3A)DFT ) [(1A)CASPT2 - (1A)DFT] -
[(3A)CASPT2 - (3A)DFT] (1)
Acknowledgment. We thank the NIH (GM47365 to W.B.T.
and a NRSA postdoctoral fellowship to B.F.G.), the NSF (CHE-
0203346 to C.J.C.), and the University of Minnesota (Lando-
NSF Research Education for Undergraduates grant to N.H.,
Louise T. Dosdall Fellowship to N.W.A.) for providing financial
support for this research. The APS ChemMatCARS 15-ID-C is
principally supported by the National Science Foundation/
Department of Energy under grant CHE-0087817, and by the
Illinois board of higher education. The APS is supported by
the U.S. Department of Energy, Basic Energy Sciences, under
Contract No. W-31-109-Eng-38. Finally, we thank L. Que, Jr.
and J. Lipscomb for access to resonance Raman and EPR
spectroscopy facilities and A. M. Reynolds for assistance with
initial resonance Raman data acquisition.
(67) Andersson, K.; Malmqvist, P. A.; Roos, B. O. J. Chem. Phys. 1992, 96,
1218.
(68) The situation is not the same for 2:1 adducts of copper and dioxygen, that
is, the bis(µ-oxo)dicopper(III) and (µ-η2:η2-peroxo)dicopper(II) complexes.
For discussion of CASPT2 versus DFT methods in these systems, see ref
48.
(69) Karlstrom, G.; Lindh, R.; Malmqvist, P. A.; Roos, B. O.; Ryde, U.;
Veryazov, V.; Widmark, P. O.; Cossi, M.; Schimmelpfennig, B.; Neogrady,
P.; Seijo, L. Comput. Mater. Sci. 2003, 28, 222.
(70) Barandiaran, Z.; Seijo, L. Can. J. Chem. 1992, 70, 409.
(71) Pierloot, K.; Dumez, B.; Widmark, P. O.; Roos, B. O. Theor. Chim. Acta
1995, 90, 87.
(72) Binkley, J. S.; Pople, J. A.; Hehre, W. J. J. Am. Chem. Soc. 1980, 102,
939.
(73) Hehre, W. J.; Stewart, R. F.; Pople, J. A. J. Chem. Phys. 1969, 51, 2657.
Supporting Information Available: Additional figures and
results of the theoretical calculations and X-ray crystallographic
data (CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
JA057745V
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3458 J. AM. CHEM. SOC. VOL. 128, NO. 10, 2006