A modular approach toward regulating the secondary coordination sphere of metal ions: Differential dioxygen activation assisted by intramolecular hydrogen bonds

Article abstract of DOI:10.1021/ja063935+

Metal ion function depends on the regulation of properties within the primary and second coordination spheres. An approach toward studying the structure-function relationships within the secondary coordination sphere is to construct a series of synthetic complexes having constant primary spheres but structurally tunable secondary spheres. This was accomplished through the development of hybrid urea-carboxamide ligands that provide varying intramolecular hydrogen bond (C-bond) networks proximal to a metal center. Convergent syntheses prepared ligands [(N′-tert-butylureayl)-N- ethyl]-bis(N″-R-carbamoylmethyl)amine (H₄1^R) and bis[(N′-tert-butylureayl)-N-ethyl]-(N″-R-carbamoylmethyl)amine (H₅2^R), where R = isopropyl, cyclopentyl, and (S)-(-)-α-methylbenzyl. The ligands with isopropyl groups H ₄1^iPr and H₅2^iPr were combined with tris[(N′-tert-butylureayl)-N-ethyl]amine (H₆buea) and bis(N-isopropylcarbamoylmethyl)-amine (H₃O^iPr) to prepare a series of Co(II) complexes with varying H-bond donors. [Co^IIH ₂2^iP7]^- (two H-bond donors), [Co ^IIH1^iPr]^- (one H-bond donor), and [Co ^IIO^iPr]^- (no H-bond donors) have trigonal monopyramidal primary coordination spheres as determined by X-ray diffraction methods. In addition, these complexes have nearly identical optical and EPR properties that are consistent with S = 3/2 ground states. Electrochemical studies show a linear spread of 0.23 V in anodic potentials (E_pa) with [Co^IIH₂2^iPr]^- being the most negative at -0.385 V vs [Cp₂Fe]⁺/[Cp₂Fe]. The properties of [Co^IIH₃buea]^- (H₃buea, tris[(N′-tert-butylureaylato)-N-ethyl]aminato that has three H-bond donors) appears to be similar to that of the other complexes based on spectroscopic data. [Co^IIH₃buea]^- and [Co ^IIH₂2^iPr]^- react with 0.5 equiv of dioxygen to afford [Co^IIIH₃buea(OH)]^- and [Co^IIIH₂2^iPr(OH)]^-. Isotopic labeling studies confirm that dioxygen is the source of the oxygen atom in the hydroxo ligands: [Co^IIIH₃buea(¹⁶OH)] ^- has a ν(O-H) band at 3589 cm^-1 that shifts to 3579 cm^-1 in [Co^IIIH₃buea(¹⁸OH)] ^-; [Co^IIIH₂2^iPr(OH)]^- has ν(¹⁶O-H) = 3661 and ν(¹⁸O-H) = 3650 cm ^-1. [Co^IIH1^iPr]^- does not react with 0.5 equiv of O₂; however, treating [Co^IIH1 ^iPr]^- with excess dioxygen initially produces a species with an X-band EPR signal at g = 2.0 that is assigned to a Co-O₂ adduct, which is not stable and converts to a species having properties similar to those of the Co^III-OH complexes. Isolation of this hydroxo complex in pure form was complicated by its instability in solution (k_int = 2.5 × 10^-7 M min^-1). Moreover, the stability of the Co^III-OH complexes is correlated with the number of H-bond donors within the secondary coordination sphere; [Co^IIIH₃buea(OH) ]^- is stable in solution for days, whereas [Co^IIIH ₂2^iPr(OH)]^- decays with a k_int = 5.9 × 10^-8 M min^-1. The system without any intramolecular H-bond donors [Co^IIO^iPr]^- does not react with dioxygen, even when O₂ is in excess. These findings indicate a correlation between dioxygen binding/activation and the number of H-bond donors within the secondary coordination sphere of the cobalt complexes. Moreover, the properties of the secondary coordination sphere affect the stability of the Co^III-OH complexes with [Co^IIIH ₃buea(OH)]^- being the most stable. We suggest that the greater number of intramolecular H-bonds involving the hydroxo ligand reduces the nucleophilicity of the Co^III-OH unit and reinforces the cavity structure, producing a more constrained microenvironment around the cobalt ion.

Full text of DOI:10.1021/ja063935+

Published on Web 11/11/2006
A Modular Approach toward Regulating the Secondary
Coordination Sphere of Metal Ions: Differential Dioxygen
Activation Assisted by Intramolecular Hydrogen Bonds
Robie L. Lucas,† Matthew K. Zart,† Jhumpa Murkerjee,†,§ Thomas N. Sorrell,‡
Douglas R. Powell,† and A. S. Borovik*,†,§
Contribution from the Department of Chemistry, UniVersity of Kansas, 2010 Malott Hall, 1251
Wescoe Hall DriVe, Lawrence, Kansas 66045, and Department of Chemistry, UniVersity of
North Carolina, Chapel Hill, North Carolina 27599
Received June 5, 2006; E-mail: aborovik@uci.edu
Abstract: Metal ion function depends on the regulation of properties within the primary and second coordi-
nation spheres. An approach toward studying the structure-function relationships within the secondary
coordination sphere is to construct a series of synthetic complexes having constant primary spheres but
structurally tunable secondary spheres. This was accomplished through the development of hybrid urea-
carboxamide ligands that provide varying intramolecular hydrogen bond (H-bond) networks proximal to a
metal center. Convergent syntheses prepared ligands [(N′-tert-butylureayl)-N-ethyl]-bis(N′′-R-carbamoyl-
methyl)amine (H41R) and bis[(N′-tert-butylureayl)-N-ethyl]-(N′′-R-carbamoylmethyl)amine (H52R), where R
) isopropyl, cyclopentyl, and (S)-(-)-R-methylbenzyl. The ligands with isopropyl groups H41iPr and H52iPr
were combined with tris[(N′-tert-butylureayl)-N-ethyl]amine (H6buea) and bis(N-isopropylcarbamoylmethyl)-
amine (H30iPr) to prepare a series of Co(II) complexes with varying H-bond donors. [CoIIH22iPr]- (two H-bond
donors), [CoIIH1iPr - (one H-bond donor), and [CoII0iPr -
] ] (no H-bond donors) have trigonal monopyramidal
primary coordination spheres as determined by X-ray diffraction methods. In addition, these complexes
3
have nearly identical optical and EPR properties that are consistent with S )
/ ground states.
2
Electrochemical studies show a linear spread of 0.23 V in anodic potentials (Epa) with [CoIIH22iPr -
] being
the most negative at -0.385 V vs [Cp2Fe]+/[Cp2Fe]. The properties of [CoIIH3buea]- (H3buea, tris[(N′-tert-
butylureaylato)-N-ethyl]aminato that has three H-bond donors) appears to be similar to that of the other
complexes based on spectroscopic data. [CoIIH3buea]- and [CoIIH22iPr -
] react with 0.5 equiv of dioxygen
to afford [CoIIIH3buea(OH)]- and [CoIIIH22iPr(OH)]-. Isotopic labeling studies confirm that dioxygen is the
source of the oxygen atom in the hydroxo ligands: [CoIIIH3buea(16OH)]- has a ν(O-H) band at 3589 cm-1
that shifts to 3579 cm-1 in [CoIIIH3buea(18OH)]-; [CoIIIH22iPr(OH)]- has ν(16O-H) ) 3661 and ν(18O-H) )
3650 cm-1. [CoIIH1iPr]- does not react with 0.5 equiv of O2; however, treating [CoIIH1iPr]- with excess dioxygen
initially produces a species with an X-band EPR signal at g ) 2.0 that is assigned to a Co-O2 adduct,
which is not stable and converts to a species having properties similar to those of the CoIII-OH complexes.
Isolation of this hydroxo complex in pure form was complicated by its instability in solution (kint ) 2.5 ×
10-7 M min-1). Moreover, the stability of the CoIII-OH complexes is correlated with the number of H-bond
donors within the secondary coordination sphere; [CoIIIH3buea(OH)]- is stable in solution for days, whereas
[CoIIIH22iPr(OH)]- decays with a kint ) 5.9 × 10-8 M min-1. The system without any intramolecular H-bond
donors [CoII0iPr]- does not react with dioxygen, even when O2 is in excess. These findings indicate a correla-
tion between dioxygen binding/activation and the number of H-bond donors within the secondary coordination
sphere of the cobalt complexes. Moreover, the properties of the secondary coordination sphere affect the
stability of the CoIII-OH complexes with [CoIIIH3buea(OH)]- being the most stable. We suggest that the
greater number of intramolecular H-bonds involving the hydroxo ligand reduces the nucleophilicity of the
CoIII-OH unit and reinforces the cavity structure, producing a more constrained microenvironment around
the cobalt ion.
Introduction
has led to the development of multidentate ligands that aid in
controlling the chemistry at the metal center. Many of these
ligands are designed to influence the primary coordination
Transition metal complexes are used in a variety of applica-
tions, including as reagents for chemical synthesis.1 This interest
(1) For selected recent reviews: (a) Nakamura, I.; Yamamoto, Y. Chem. ReV.
2004, 104, 2127-2198. (b) Trost, B. M.; Crawley, M. L. Chem. ReV. 2003,
103, 2921-2943. (c) Uma, R.; Cre´visy, C.; Gre´e, R. Chem. ReV. 2003,
103, 27-51. (d) Transition Metals for Organic Synthesis, 2nd ed.; Beller,
M., Bolm, C., Eds.; Wiley-CH: Weinheim, Germany, 2004; Vol. 1-2.
† University of Kansas.
‡ University of North Carolina.
§ Current address: Department of Chemistry, University of California,
Irvine, CA 92697.
9
15476
J. AM. CHEM. SOC. 2006, 128, 15476-15489
10.1021/ja063935+ CCC: $33.50 © 2006 American Chemical Society

Regulating Secondary Coordination Sphere of Metal Ions
A R T I C L E S
Figure 1. Series of ligands and complexes having varied intramolecular H-bond networks.
sphere of a metal complex, which ultimately affects properties
related to electronic structure and acidity.2 While often over-
looked, the secondary coordination sphere also can have a
crucial role in determining the functional properties of metal
complexes. In fact, it is becoming increasingly apparent that
managing both spheres around a metal ion is necessary to
achieve desirable functions.
Placing hydrogen bond (H-bond) donors and acceptors
proximal to a metal center is one approach for controlling the
secondary coordination sphere. The key impetus for this
approach comes from structural studies on metalloproteins that
show active site architectures with H-bonds involving ligands
coordinated to the metal ion(s).3 These noncovalent interactions
assist in modulating structural features around the active metal
center(s) that, in turn, help regulate protein function. Transferring
these structure-function relationships to synthetic systems is
often difficult because H-bonds tend to form intermolecularly
with other species in the reaction milieu; the sought after
intramolecular interactions are usually obtainable only when
the H-bond donors/acceptors are tethered to a rigid framework.
Nevertheless, there are now examples of systems that form
intramolecular H-bonds to exogenous ligands, most often in
studies aimed at molecular recognition processes.4
Our group5 and others6 have used tripodal ligands as a means
to position H-bond donors or acceptors near metal centers. We
have developed urea-based tripods that create a rigid H-bonding
cavity around vacant coordination sites when the ligand binds
to a metal ion. For instance, the symmetrical ligand tris[(N′-
tert-butylureaylato)-N-ethyl]aminato ([H3buea]3-) places three
H-bond donors within the interior of a cavity adjacent to a
coordinated metal ion (Figure 1). We have shown that iron(II)
and manganese(II) complexes of [H3buea]3- bind and activate
dioxygen to form MIII-O complexes in which three intra-
molecular H-bonds are formed with the terminal oxo ligand.
Complexes of [H3buea]3- contain a fixed number of H-bonds
within the secondary coordination sphere, producing a relatively
constant H-bond network; in fact, most reported systems to date
have a set amount of H-bond donors/acceptors. To fully under-
stand the effects of H-bonds on metal-mediated processes, it is
necessary to know how Varying H-bond networks correlate with
changes in function. An approach to probe these structure-
function correlations requires the development of structurally
tunable cavities, which can be accomplished through the design
and preparation of ligands that provide similar primary coordi-
nation spheres but different architectures and noncovalent
interactions in the secondary coordination sphere. Few systems
(2) Constable, E. C. Metals and Ligand ReactiVity; VCH: Weinheim, Germany,
1996.
(5) (a) Hammes, B. S.; Young, V. G., Jr.; Borovik, A. S. Angew. Chem., Int.
Ed. 1999, 38, 666-669. (b) Shirin, Z.; Hammes, B. S.; Young, V. G., Jr.;
Borovik, A. S. J. Am. Chem. Soc. 2000, 122, 1836-1837. (c) MacBeth, C.
E.; Golombek, A. P.; Young, V. G., Jr.; Yang, C.; Kuczera, K.; Hendrich,
M. P.; Borovik, A. S. Science 2000, 289, 938-941. (d) MacBeth, C. E.;
Hammes, B. S.; Young, V. G., Jr.; Borovik, A. S. Inorg. Chem. 2001, 40,
4733-4741. (e) Gupta, R. G.; MacBeth, C. E.; Young, V. G., Jr.; Borovik,
A. S. J. Am. Chem. Soc. 2002, 124, 1136-1137. (f) Gupta, R.; Borovik,
A. S. J. Am. Chem. Soc. 2003, 125, 13234-13242. (g) Zart, M. K.; Sorrell,
T. N.; Powell, D.; Borovik, A. S. J. Chem. Soc., Dalton Trans. 2003, 1986-
1992. (h) MacBeth, C. E.; Gupta, R.; Mitchell-Koch, K. M.; Young, V.
G., Jr.; Lushington, G. H.; Thompson, W. H.; Hendrich, M. P.; Borovik,
A. S. J. Am. Chem. Soc. 2004, 126, 2556-2567. (i) Larsen, P. L.; Gupta,
R.; Powell, D. R.; Borovik, A. S. J. Am. Chem. Soc. 2004, 126, 6622-
6623. (j) Borovik, A. S. Acc. Chem. Res. 2005, 38, 54-61. (k) Lucas, R.
L.; Powell, D. R.; Borovik, A. S. J. Am. Chem. Soc. 2005, 127, 11597-
11598. (l) Zinn, P. J.; Powell, D. R.; Hendrich, M. P.; Sorrell, T. N.;
Borovik, A. S. Inorg. Chem. 2006, 45, 3484-3486.
(3) (a) Lu, Y.; Valentine, J. S. Curr. Opin. Struct. Biol. 1997, 7, 495-500. (b)
Regan, L. TIBS 1995, 20, 280-285.
(4) Selected relevant examples: (a) Jameson, G. B.; Drago, R. S. J. Am. Chem.
Soc. 1985, 107, 3017-3020. (b) Momenteau, M.; Reed, C. A. Chem. ReV.
1994, 94, 659-698. (c) Collman, J. P. Inorg. Chem. 1997, 36, 5145-
5155. (d) Collman, J. P.; Zhang, X.; Wong, K.; Brauman, J. J. Am. Chem.
Soc. 1994, 116, 6245-6251. (e) Wuenschell, G. E.; Tetreau, C.; Lavalette,
D.; Reed, C. A. J. Am. Chem. Soc. 1992, 114, 3346-3355. (f) Chang, C.
K.; Liang, Y.; Avile´s, G. J. Am. Chem. Soc. 1995, 117, 4191-4192. (g)
Yeh, C.-Y.; Chang, C. J.; Nocera, D. G. J. Am. Chem. Soc. 2001, 123,
1513-1514. (h) Rudkevich, D. M.; Verboom, W.; Brzozka, Z.; Palys, M.
J.; Stauthamer, W. P. R. V.; Van Hummel, G. J.; Franken, S. M.; Harkema,
S.; Engbersen, J. F. J.; Reinhoudt, D. N J. Am. Chem. Soc. 1994, 116,
4341-4351. (i) Kickham, J. E.; Loeb, S, L.; Murphy, S. L. J. Am. Chem.
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A R T I C L E S
Lucas et al.
Experimental Section
have been reported with these attributes, the closest examples
being those involving polypyridine ligands having various num-
bers of amino groups available for hydrogen bonding.7,8 Masuda
has used these ligands to prepare a series of CuII-azide com-
plexes: spectroscopic and structural characterization indicated
that as the number of amino groups on the tripodal ligands in-
creased, the geometry around the Cu(II) ion changed from ideal
trigonal bipyramidal to a geometry between trigonal bipyramidal
and square pyramidal.7 The change in coordination geometry
was attributed to increased steric repulsion between the amino
groups and the coordinated azide ion bonded to the Cu(II) ion.
In a separate study, Mareque-Rivas probed the effects of
H-bonds on the acidity of Zn(II)-water complexes;8a,b the place-
ment of two H-bond donors proximal to the Zn(II)-bound water
molecule enhances its acidity nearly 2 orders of magnitude.
The limited number of transition metal complexes with varied
H-bond networks is directly linked to the paucity of ligands
that produce a constant primary coordination sphere while
conveniently allowing systematic adjustments to the secondary
coordination sphere. We have therefore developed tripodal
urea-carboxamide hybrid ligands that are prepared via straight-
forward convergent syntheses. The ligands9,10 H52R and H41R
(Figure 1) contain at least one urea arm and, together with H6-
buea and H30R,11 constitute a series of ligands whose metal
complexes have equivalent primary coordination spheres but
different H-bond networks within the secondary coordination
sphere. The assessment of structure-function relationships is
illustrated with a series of Co(II) complexes having similar
coordination geometries and spectroscopic properties but dif-
fering in their abilities to bind and activate dioxygen.
General Methods. All reagents were purchased from commercial
sources and used as received, unless otherwise noted. Solvents were
purified according to standard procedures. Anhydrous solvents were
purchased from Aldrich. Potassium hydride (KH) as a 30% dispersion
in mineral oil was filtered with a medium porosity glass frit and washed
5 times each with pentane and Et2O. The solid KH was dried under a
vacuum and stored under an inert atmosphere. The syntheses of ligands
and their intermediates were carried out under a dinitrogen atmosphere.
The syntheses of metal complexes were conducted in a Vacuum
Atmospheres, Co. drybox under an argon atmosphere. Dioxygen was
dried on a Drierite gas purifier purchased from Fischer Scientific. 18O2
was obtained from ICON Isotopes (Summit, NJ). Elemental analyses
were accomplished at Desert Analytics, Tucson, AZ. The preparations
of H30 and H6buea have been published previously.5b,11b The synthesis
of [CoIIIH3buea(OH)]- using water as the source of hydroxide has also
been reported.5a
Preparative Methods. 1-tert-Butyl-3-(2-chloroethyl)urea (3) To
a suspension of 2-chloroethylamine hydrochloride (11.54 g, 99.49
mmol) in 100 mL of THF was added NaHCO3 (9.20 g, 110 mmol).
The mixture was treated dropwise with tert-butyl isocyanate (12.5 mL,
109 mmol) and allowed to stir overnight. The mixture was then filtered,
and the white solid was washed with THF. The colorless filtrate was
concentrated under reduced pressure to a white solid, which was
recrystallized from Et2O and dried under a vacuum to 14.5 g (81%).
1
Mp 99-101 °C; H NMR (400 MHz, DMSO-d6) δ 5.93 (1H, t, J )
6.0 Hz, CH2NH), 5.85 (1H, s, NHsC(CH3)3), 3.55 (2H, t, J ) 6.0 Hz,
CH2CH2Cl), 3.27 (2H, dt, J ) 6.0 Hz, NHsCH2CH2), 1.21 (9H, s,
C(CH3)3); 13C NMR (500 MHz, CDCl3) δ 157.7, 50.1, 44.7, 41.7, 29.5;
FTIR (Nujol) 3367 (NsH), 3348 (NsH), 1632 (CdO); HRMS
(ES+): Exact mass calcd for C7H16N2OCl [M + H], 179.0951. Found
179.0958.
1-tert-Butyl-3-(2-phthalimidooethyl)urea (4). A solution of chloride
3 (14.38 g, 80.49 mmol) in 80 mL of anhydrous DMF was treated
with potassium phthalimide (29.82 g, 161.0 mmol), and the resulting
mixture was heated at 120 °C for 3 h with stirring. The pale pink
mixture was brought to rt and then poured into 400 mL of H2O to
produce a white precipitate, which was filtered, washed with H2O, and
dried overnight under a vacuum at 70 °C. The white solid was
recrystallized from acetone/hexanes and dried under a vacuum to 17.04
(6) (a) Harata, M.; Jitsukawa, K.; Masuda, H.; Einaga, H. Chem. Lett. 1995,
61-62. (b) Ogo, S.; Wada, S.; Watanabe, Y.; Iwase, M.; Wada, A.; Harata,
M.; Jitsukawa, K.; Masuda, H.; Einaga, H. Angew. Chem., Int. Ed. 1998,
37, 2102-2104. (c) Berreau, L. M.; Allred, R. A.; Makowska-Grzyska,
M.; Arif, A. M. Chem. Commun. 2000, 1423-1424. (d) Berreau, L. M.;
Makowska-Grzyska, M. M.; Arif, A. M. Inorg. Chem. 2001, 40, 2212-
2213. (e) Garner, D. K.; Fitch, S. B.; McAlexander, L. H.; Bezold, L. M.;
Arif, A. M.; Berreau, L. M. J. Am. Chem. Soc. 2002, 124, 9970-9971. (f)
Ogo, S.; Yamahara, R.; Roach, M.; Suenobu, T.; Aki, M.; Ogura, T.;
Kitagawa, T.; Masuda, H.; Fukuzumi, S.; Watanabe, Y. Inorg. Chem. 2002,
41, 5513-5520. (g) Cheruzel, L. E.; Wang, J.; Mashuta, M. S.; Buchanan,
R. M. Chem. Commun. 2002, 2166-2167. (h) Tubbs, K. J.; Fuller, A. L.;
Bennett, B.; Arif, A. M.; Berreau, L. M. Inorg. Chem. 2003, 42, 4790-
4791. (i) Mareque-Rivas, J. C.; Torres Mart´ın de Rosales, R.; Parsons, S.
Dalton Trans. 2003, 2156-2163. (j) Mareque-Rivas, J. C.; Torres Mart´ın
de Rosales, R.; Parsons, S. Chem. Commun. 2004, 610-611. (k) Mareque-
Rivas, J. C.; Salvagni, E.; Parsons, S. Chem. Commun. 2004, 460-461. (l)
Mareque-Rivas, J. C.; Salvagni, E.; Parsons, S. Dalton Trans. 2004, 4185-
4192. (m) Cheruzel, L. E.; Cecil, M. R.; Edison, S. E.; Mashuta, M. S.;
Baldwin, M. J.; Buchanan, R. M. Inorg. Chem. 2006, 45, 3191-3202.
(7) Wada, A.; Honda, Y.; Yamaguchi, S.; Nagatomo, S.; Kitagawa, T.;
Jitsukawa, K. Inorg. Chem. 2004, 43, 5725-5735.
1
g (73%). Mp 199-200 °C; H NMR (400 MHz, DMSO-d6) δ 7.83
(4H, m, ArH), 5.73 (1H, t, J ) 6.0 Hz, CH2NH), 5.55 (1H, s, NH-
C(CH3)3), 3.57 (2H, t, J ) 5.7 Hz, CH2CH2NPhth), 3.23 (2H, dt, J )
5.7, 6.0 Hz, NHsCH2CH2), 1.06 (9H, s, C(CH3)3); 13C NMR (500 MHz,
CDCl3) δ 168.6, 157.1, 134.0, 132.0, 123.3, 50.4, 39.3, 38.3, 29.3; FTIR
(KBr) 3364 (NsH), 3340 (NsH), 1720 (imide CdO), 1709 (imide
CdO), 1631 (urea CdO); HRMS (FAB+): Exact mass calcd for
C15H20N3O3 [M + H], 290.1505. Found 290.1505.
1-(2-Aminoethyl)-3-tert-butylurea (5). A suspension of phthalimide
4 (10.75 g, 37.15 mmol) in 375 mL of EtOH was treated with hydrazine
monohydrate (9.30 g, 186 mmol) and heated to reflux, resulting in a
homogeneous solution. Over the course of refluxing for 3 h a volumi-
nous white ppt (phthalhydrazide) formed. The mixture was cooled to
rt, and the precipitate was filtered and washed with EtOH. The colorless
filtrate was concentrated under reduced pressure to an oil, which was
treated with 95 mL of CHCl3, resulting in precipitation of more
phthalhydrazide. The ppt was filtered and washed with CHCl3. The
filtrate was concentrated to an oil and dried under a vacuum to a white
solid weighing 5.92 g (100%). 1H NMR (500 MHz, DMSO-d6) δ 5.69
(1H, t, J ) 5.6 Hz, CH2NH), 5.67 (1H, s, NHsC(CH3)3), 2.93 (2H, dt,
J ) 5.6, 6.2 Hz, NHsCH2CH2), 2.51 (2H, t, J ) 6.2 Hz, CH2CH2-
NH2), 1.21 (9H, s, C(CH3)3); 13C NMR (500 MHz, DMSO-d6) δ 157.9,
49.3, 42.7, 42.5, 29.7; FTIR (thin film from CH2Cl2) 3350 (NsH),
1645 (CdO); HRMS (FAB+): Exact mass calcd for C7H18N3O [M +
H], 160.1450. Found 160.1469.
(8) (a) Mareque-Rivas, J. C.; Prabaharan, R.; Torres Mart´ın de Rosales, R.
Chem. Commun. 2004, 76-77. (b) Mareque-Rivas, J. C.; Prabaharan, R.;
Parsons, S. Dalton Trans. 2004, 1648-1655. (c) Mareque-Rivas, J. C.;
Salvagni, E.; Parsons, S. Dalton Trans. 2004, 4185-4192.
(9) The bold numbers in the abbreviations for the hybrid ligands denote the
number of H-bond donating groups; H41R and H52R have one and two
H-bond donors, respectively. The ligands containing only amide groups,
H30R has no H-bond donors and is thus indicated by the zero. The ligand
with three urea groups, H6buea has been reported previously and its name
is unchanged for consistency.
(10) A report containing these ligands in iron-amido chemistry has recently
appeared: Lucas, R. L.; Powell, D. R.; Borovik, A. S. J. Am. Chem. Soc.
2005, 127, 11597-11598
(11) (a) Ray, M.; Yap, G. P. A.; Rheingold, A. L.; Borovik, A. S. Chem.
Commun. 1995, 1977-1978. (b) Ray, M.; Golombek, A. P.; Hendrich, M.
P.; Young, V. G., Jr.; Borovik, A. S. J. Am. Chem. Soc. 1996, 118, 6084-
6085. (c) Ray, M.; Golombek, A. P.; Hendrich, M. P.; Yap, G. P. A.; Liable-
Sands, L. M.; Rheingold, A. L.; Borovik, A. S. Inorg. Chem. 1999, 38,
3110-3115. (d) Ray, M.; Hammes, B. S.; Yap, G. P. A.; Rheingold, A.
L.; Borovik, A. S. Inorg. Chem. 1998, 37, 1527-1532. (e) Shirin, Z.;
Young, V. G.; Borovik, A. S. Chem. Commun. 1997, 4, 1967-1968. (f)
Hammes, B. S.; Maldonado-Ramos, D.; Yap, G. P. A.; Liable-Sands, L.;
Rheingold, A. L.; Borovik, A. S. Inorg. Chem. 1997, 36, 3210-3211.
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Regulating Secondary Coordination Sphere of Metal Ions
A R T I C L E S
1
Bis[(N′-tert-butylureayl)-N-ethyl]benzylamine (6). A mixture of
benzylamine (6.11 g, 57.0 mmol), chloride 3 (21.38 g, 119.7 mmol),
Et3N (13.3 g, 131 mmol), and NaI (85 mg, 0.57 mmol) in 250 mL of
THF was refluxed for 48 h. The mixture was cooled to rt, and Et3N‚
HCl that precipitated from the reaction mixture was removed by
filtration. The filtrate was concentrated under reduced pressure to an
orange oil that solidified upon standing overnight. The solid was
triturated with EtOAc to produce a white solid that was filtered, washed
with EtOAc followed by Et2O, and dried under a vacuum to 15.18 g.
The filtrate from the trituration was concentrated to an orange oil and
then eluted through a plug of silica gel with EtOAc. The pale yellow
solid obtained was filtered and washed with Et2O to give a white solid.
The solid was dried under a vacuum to 1.90 g, giving a combined yield
Mp 108-109 °C; H NMR (400 MHz, CDCl3) δ 7.34 (5H, m, Ars
H), 6.73 (1H, bs, COsNH), 5.10 (1H, m, NHsCHCH3), 3.90 (1H, d,
J ) 14 Hz, BrCH(H)sCO), 3.85 (1H, d, J ) 14 Hz, BrCH(H)sCO),
1.53 (3H, d, J ) 7.0 Hz, CHCH3); 13C NMR (400 MHz, CDCl3) δ
164.4, 142.3, 128.8, 127.6, 126.0, 49.6, 29.3, 21.6; FTIR (KBr) 3263
(NsH), 1648 (CdO); [R]20 -26.8 (c 0.250, CHCl3); LRMS
(FAB+): Found for C10H13BrNO [M + H], 242.1.
D
Bis[(N′ -tert-butylureayl)- N-ethyl]-(N′′-isopropylcarbamoyl-
methyl)amine (H52iPr). A mixture of secondary amine 7 (3.98 g, 13.2
mmol), bromide 8 (2.61 g, 14.5 mmol), and Et3N (1.54 g, 15.2 mmol)
in 65 mL of THF was refluxed overnight. The mixture was cooled to
rt, and Et3N‚HBr that precipitated from the reaction mixture was
removed by filtration. The pale yellow filtrate was concentrated under
reduced pressure to an oil that was triturated with EtOAc to produce a
white solid. The solid was isolated via filtration, washed with EtOAc,
and dried under a vacuum to afford 3.96 g (75%) of H52iPr. Mp 176-
1
of 17.08 g (77%). Mp 173-175 °C; H NMR (400 MHz, DMSO-d6)
δ 7.34-7.22 (5H, m, ArH), 5.75 (2H, t, J ) 5.7 Hz, CH2NH), 5.71
(2H, s, NHsC(CH3)3), 3.57 (2H, s, CH2Ph), 3.03 (4H, dt, J ) 5.7, 6.0
Hz, NHsCH2CH2), 2.39 (4H, t, J ) 6.0 Hz, CH2CH2NBn), 1.23 (18H,
s, C(CH3)3); 13C NMR (500 MHz, CDCl3) δ 158.5, 139.7, 129.0, 127.9,
126.8, 59.3, 55.6, 49.9, 37.8, 29.6; FTIR (KBr) 3377 (NsH), 3274
(NsH), 1632 (CdO); HRMS (FAB+): Exact mass calcd for C21H38N5O2
[M + H], 392.3026. Found 392.3033.
1
178 °C; H NMR (400 MHz, DMSO-d6) δ 7.43 (1H, d, J ) 8.2 Hz,
NHsCH(CH3)2), 5.79 (2H, t, J ) 5.5 Hz, NHsCH2CH2), 5.72 (2H, s,
(CH3)3CsNH), 3.88 (1H, m, CH(CH3)2), 3.01 (4H, dt, J ) 5.5, 6.0
Hz, NHCH2CH2), 3.00 (2H, s, CH2sCO), 2.46 (4H, t, J ) 6.0 Hz,
NHCH2CH2), 1.22 (18H, s, (CH3)3C), 1.08 (6H, d, J ) 6.6 Hz, CH-
(CH3)2); 13C NMR (500 MHz, CDCl3) δ 170.2, 159.0, 60.7, 57.0, 50.1,
40.9, 38.4, 29.7, 22.6; FTIR (Nujol) 3404 (NsH), 3348 (NsH), 3285
(NsH), 3256 (NsH), 1673 (amide CdO), 1630 (urea CdO); HRMS
(ES+): Exact mass calcd for C19H41N6O3 [M + H], 401.3240. Found
401.3230.
Bis[(N′-tert-butylureayl)-N-ethyl]amine (7). To a solution of 6 (7.86
g, 20.1 mmol) in 150 mL of MeOH and 75 mL of cyclohexene was
added 10% Pd/C (750 mg). The suspension refluxed for 4 h. After
cooling to rt the mixture was filtered through a pad of Celite. The filtrate
was concentrated under reduced pressure, and the residue was treated
with Et2O to produce a white solid. The white solid was filtered, washed
with Et2O, and dried under a vacuum to 5.19 g (86%). Mp 177-179
Bis[(N′-tert-butylureayl)-N-ethyl]-(N′′-cyclopentylcarbamoyl-
methyl)amine (H52cyp). Following a similar protocol used for the
preparation of H52iPr, reaction between secondary amine 7 (1.00 g, 3.31
mmol) and bromide 9 (752 mg, 3.65 mmol) gave 850 mg (60%) of
H52cyp. Mp 133-136 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.50 (1H,
d, J ) 8.0 Hz, COsNHscyp), 5.76 (2H, t, J ) 5.5 Hz, COsNHs
CH2CH2), 5.69 (2H, s, (CH3)3CsNH), 4.01 (1H, m, COsNHsCH),
3.01 (2H, s, CH2sCO), 3.00 (4H, dt, J ) 6.0 Hz, NHCH2CH2), 2.46
(4H, t, J ) 6.0 Hz, NHCH2CH2), 1.79 (2H, m, cypCH2), 1.64 (2H, m,
cypCH2), 1.50 (2H, m, cypCH2), 1.40 (2H, m, cypCH2), 1.22 (18H, s,
(CH3)3CsNH; 13C NMR (500 MHz, CDCl3) δ 170.8, 158.8, 60.8, 56.9,
50.8, 50.1, 38.5, 32.8, 29.7, 23.6; FTIR (Nujol) 3396 (NsH), 3335
(NsH), 3285 (NsH), 1673 (amide CdO), 1632 (urea CdO); HRMS
(ES+): Exact mass calcd for C21H43N6O3 [M + H], 427.3397. Found
427.3389.
1
°C; H NMR (400 MHz, DMSO-d6) δ 5.68 (2H, s, NHsC(CH3)3),
5.65 (2H, t, J ) 5.7 Hz, CH2NHsCO), 2.99 (4H, dt, J ) 5.7, 6.3 Hz,
COsNHsCH2CH2), 2.48 (4H, t, J ) 6.3 Hz, CH2CH2NHsCH2), 1.20
(18H, s, C(CH3)3); 13C NMR (500 MHz, CDCl3) δ 158.2, 50.3, 49.3,
40.0, 29.6; FTIR (KBr) 3358 (NsH), 3324 (NsH), 1635 (CdO);
HRMS (ES+): Exact mass calcd for C14H32N5O2 [M + H], 302.2556.
Found 302.2554.
N-Isopropyl-2-bromoacetamide (8). A solution of isopropylamine
(19.69 g, 333.1 mmol) dissolved in 350 mL of CH2Cl2 was cooled to
0 °C with an ice water bath. Bromoacetyl bromide (33.61 g, 166.5
mmol) was added to the solution dropwise over 15 min, during which
time a white ppt formed. The mixture was warmed to rt and stirred for
1 h, and the white ppt was filtered and washed with CH2Cl2. The
colorless filtrate was washed with 2 M HCl (1 × 175 mL) and brine
(1 × 175 mL). The solution was dried over Na2SO4, filtered, and
concentrated under reduced pressure to a white solid, which was dried
under a vacuum to 25.60 g (85%). Mp 63-64 °C (lit.12 66-67 °C); 1H
NMR (400 MHz, CDCl3) δ 6.32 (1H, bs, NH), 4.05 (1H, m, NHs
CH(CH3)2), 3.84 (2H, s, BrCH2), 1.18 (6H, d, J ) 6.6 Hz, CH(CH3)2);
13C NMR (400 MHz, CDCl3) δ 164.4, 42.3, 29.4, 22.4; FTIR (thin
film from CH2Cl2) 3285 (NsH), 1644 (CdO); LRMS (FAB+): Found
for C5H11BrNO [M + H], 180.1.
Bis[(N′-tert-butylureayl)-N-ethyl]-(N′′-(S)-(-)-R-methyl-benzyl-
carbamoylmethyl)amine (H52S-mbz). A similar protocol used for the
preparation of H52iPr was used with the following modification: the
oil obtained after concentration of the filtrate was purified by flash
chromatography over silica gel, eluting with EtOAc followed by 1:19
MeOH/EtOAc. Reaction between secondary amine 7 (1.25 g, 4.15
mmol) and bromide 10 (1.63 g, 6.73 mmol) gave 1.30 g (68%) of
H52S-mbz as a light yellow foam. H NMR (400 MHz, DMSO-d6) δ
1
8.07 (1H, d, J ) 8.3 Hz, NHsCHCH3), 7.30 (4H, m, ArH), 7.21 (1H,
m, ArH), 5.77 (2H, t, J ) 6.0 Hz, NHsCH2CH2), 5.70 (2H, s,
(CH3)3CsNH), 4.94 (1H, m, NHsCHCH3), 3.12 (1H, d, J ) 16 Hz,
NCH(H)sCO), 3.07 (1H, d, J ) 16 Hz, NCH(H)sCO), 3.04 (4H, dt,
J ) 6.0, 6.0 Hz, NHCH2CH2), 2.51 (4H, t, overlapped with residual
DMSO, NHCH2CH2), 1.39 (3H, d, J ) 7.0 Hz, CHCH3), 1.21 (18H, s,
(CH3)3C); 13C NMR (400 MHz, CDCl3) δ 170.3, 158.6, 143.6, 128.6,
127.2, 126.2, 60.1, 56.6, 50.1, 47.6, 38.3, 29.6, 21.7; FTIR (Nujol)
N-Cyclopentyl-2-bromoacetamide (9). Following a similar protocol
used for the preparation of 8, reaction between cyclopentylamine (13.53
g, 158.9 mmol) and bromoacetyl bromide (16.0 g, 79.3 mmol) gave
1
14.21 g (87%) of compound 9 as a white solid. Mp 84-85 °C; H
NMR (400 MHz, CDCl3) δ 6.44 (1H, bs, NH), 4.19 (1H, m, NHs
CH), 3.87 (2H, s, BrCH2), 2.01 (2H, m, cypCH2), 1.70 (2H, m, cypCH2),
1.63 (2H, m, cypCH2), 1.43 (2H, m, cypCH2); 13C NMR (400 MHz,
CDCl3) δ 164.8, 51.8, 32.8, 29.4, 23.6; FTIR (KBr) 3281 (NsH), 1647
(CdO); HRMS (FAB+): Exact mass calcd for C7H13BrNO [M + H],
206.0181. Found 206.0183.
3328 (NsH), 1642 (CdO); [R]20 -31.6 (c 0.250, CHCl3); HRMS
(ES+): Exact mass calcd for C24H43N6O3 [M + H], 463.3397. Found
463.3395.
D
(S)-(-)-N-R-Methylbenzyl-2-bromoacetamide (10). Following a
similar protocol used for the preparation of 8, reaction between (S)-
(-)-R-methyl-benzylamine (10.64 g, 87.80 mmol) and bromoacetyl
bromide (8.86 g, 43.9 mmol) gave 10.40 g (98%) of compound 11.
[(N′-tert-Butylureayl)-N-ethyl]-bis(N′′-isopropylcarbamoyl-methyl)-
amine (H41iPr). A mixture of amine 5 (4.50 g, 28.3 mmol), bromide 8
(10.69 g, 59.38 mmol), Et3N (6.58 g, 65.0 mmol), and NaI (85 mg,
0.57 mmol) in 140 mL of THF was refluxed for 20 h. The dark yellow
mixture, which contained Et3N‚HBr ppt, was brought to rt and concen-
trated under reduced pressure. The residue was dissolved with 140 mL
(12) Weaver, W. E.; Whaley, W. M. J. Am. Chem. Soc. 1947, 69, 515-516.
9
J. AM. CHEM. SOC. VOL. 128, NO. 48, 2006 15479

A R T I C L E S
Lucas et al.
of CH2Cl2 and washed with H2O (2 × 70 mL) and brine (1 × 70 mL).
The organic layer was dried over Na2SO4, filtered, and concentrated
to a yellow oil. The oil was eluted through a plug of silica gel with
EtOAc followed by 1:19 MeOH/EtOAc. The white solid obtained was
triturated with Et2O, filtered, and dried under a vacuum to 5.64 g (56%).
Mp 134-136 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.81 (2H, d, J )
8.0 Hz, NHsCH(CH3)2), 5.73 (1H, t, J ) 5.6 Hz, NHsCH2), 5.71
(1H, s, (CH3)3CsNH), 3.87 (2H, m, CH(CH3)2), 3.07 (4H, s, CH2s
CO), 3.02 (2H, dt, J ) 5.9, 6.0 Hz, NHCH2CH2), 2.48 (2H, t, J ) 6.2
Hz, NHCH2CH2), 1.21 (9H, s, (CH3)3C), 1.06 (12H, d, J ) 6.6 Hz,
CH(CH3)2); 13C NMR (500 MHz, CDCl3) δ 170.0, 158.2, 59.3, 57.0,
50.3, 41.2, 38.2, 29.6, 22.6; FTIR (Nujol) 3344 (NsH), 3251 (NsH),
1669 (amide CdO), 1634 (urea CdO); HRMS (FAB+): Exact mass
calcd for C17H37N5O3 [M + H], 358.2818. Found 358.2809.
[(N′-tert-Butylureayl)-N-ethyl]-bis(N′′-cyclopentyl-carbamoyl-
methyl)amine (H41cyp). A similar protocol used for the preparation of
H41iPr was used with the following modification: the oil obtained from
the CH2Cl2 layer after aqueous workup was triturated with Et2O to give
the product as a white solid. Reaction between amine 5 (2.62 g, 16.5
mmol) and bromide 9 (7.14 g, 34.6 mmol) afforded 5.37 g (80%) of
H41cyp. Mp 115-117 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.89 (2H,
d, J ) 7.6 Hz, COsNHscyp), 5.71 (1H, t, J ) 5.6 Hz, COsNHs
CH2CH2), 5.68 (1H, s, (CH3)3CsNH), 4.01 (2H, m, COsNHsCH),
3.09 (4H, s, CH2sCO), 3.00 (2H, dt, J ) 5.9, 6.1 Hz, NHCH2CH2),
2.49 (2H, t, J ) 6.4 Hz, NHCH2CH2), 1.78 (4H, m, cypCH2), 1.64
(4H, m, cypCH2), 1.49 (4H, m, cypCH2), 1.40 (4H, m, cypCH2), 1.21
(9H, s, (CH3)3CsNH); 13C NMR (500 MHz, CDCl3) δ 170.5, 158.3,
59.3, 56.9, 51.0, 50.2, 38.2, 30.0, 23.7; FTIR (Nujol) 3340 (NsH),
3278 (NsH), 1671, 1657, 1621; HRMS (ES+): Exact mass calcd for
C21H40N5O3 [M + H], 410.3131. Found 410.3120.
Co(OAc)2 (99 mg, 0.56 mmol). After the reaction was completed, 109
mg (99%) of KOAc were removed via filtration. Vapor diffusion of
Et2O into the filtrate produced aqua blue crystals, which were filtered,
washed with Et2O, and dried under a vacuum to 244 mg (81%). Anal.
Calcd (found) for K[CoIIH1iPr]‚DMA, C21H41CoKN6O4: C, 46.74
(46.35); H, 7.66 (7.83); N, 15.57 (15.51); FTIR (Nujol, cm-1) ν(NH)
3425, ν(CO) 1645, 1609, 1578, 1566; λmax (DMA, nm (ꢀ, M-1 cm-1))
385 (23), 588 (180), 608 (160); X-band EPR (DMA, 4 K) g ) 4.0,
2.0.
Potassium {bis[(N-isopropylcarbamoylmethyl)aminato]cobaltate-
(II)} K[CoII0iPr] was prepared following the procedure outlined for
K[CoIIH22iPr] using H30iPr (201.6 mg, 0.641 mmol), 10 mL of anhydrous
DMA, KH (78.2 mg, 1.95 mmol), and Co(OAc)2 (116 mg, 0.655 mmol).
KOAc (123 mg, 97%) was removed via filtration, and vapor diffusion
of Et2O into the filtrate produced 298 mg (94%) of the product as blue
crystals. Anal. Calcd (found) for K[CoIIH1iPr]‚DMA, C19H36-
CoKN5O4: C, 45.96 (46.23); H, 7.31 (7.39); N, 14.10 (14.02); FTIR
(Nujol, cm-1) 1647, 1578, 1266, 1155; λmax (DMA, nm (ꢀ, M-1 cm-1))
401 (17), 583 (160), 606 (150); X-band EPR (DMA, 4 K) g ) 4.0, 2.0.
Potassium {bis[(N′-tert-butylureayl)-N-ethyl]-(N′′-isopropylcarba-
moylmethyl)-aminato(hydroxo)cobaltate(III)} K[CoIIIH22iPr(OH)].
Method A: K[CoH22iPr] (50 mg, 0.10 mmol) dissolved in 2.0 mL of
DMA was treated with 1.2 mL of O2 (0.051 mmol at T ) 295 K and
P ) 0.982 atm). After 1 h of stirring the volume was reduced by half
under reduced pressure and treated with enough diethyl ether to pre-
cipitate the product, as a red solid (47 mg, 94%). Method B: A solution
of the ligand H52iPr (100 mg, 0.250 mmol) dissolved in 4 mL anhydrous
DMA was treated with solid KH (30 mg, 0.75 mmol). The mixture
was stirred until gas evolution ceased. Co(OAc)2 (44 mg, 0.25 mmol)
was added to the pale yellow solution, and stirring was continued for
30 min. The aqua blue mixture was treated with dry O2 (0.55 equiv,
3.3 mL, 0.14 mmol), and the resulting dark red mixture stirred for 1 h.
The mixture was placed under a vacuum for a few minutes to remove
unreacted O2. KOAc was then removed by filtration, and the filtrate
was concentrated in vacuo. Treatment of the residue with Et2O produced
a dark red solid that was filtered, washed with Et2O, and dried under
a vacuum to 120 mg (94%). Anal. Calcd (found) for K[CoIIIH22iPr(OH)],
C19H38CoKN6O4: C, 44.52 (44.83); H, 7.47 (7.66); N, 16.40 (16.72);
FTIR (Nujol, cm-1) ν(16OH/18OH) 3662/3651, ν(NH) 3300, 3190,
ν(CO) 1588; λmax (DMF, nm (ꢀ, M-1 cm-1)) 295 (4700), 394 (sh), 475
(1400), 794 (160).
[(N′-tert-Butylureayl)-N-ethyl]-bis(N′′-(S)-(-)-R-methyl-benzyl-
carbamoylmethyl)amine (H41S-mbz). A similar protocol used for the
preparation of H41iPr was used with the following modification: the
oil obtained after extraction and drying of the CH2Cl2 was purified by
flash chromatography over silica gel, eluting with 1:1 acetone/hexanes.
Reaction between amine 5 (0.79 g, 5.0 mmol) and bromide 10 (2.52 g,
10.4 mmol) gave 1.43 g (60%) of H41S-mbz as a white foam. 1H NMR
(400 MHz, DMSO-d6) δ 8.46 (2H, d, J ) 8.2 Hz, NHsCHCH3), 7.33-
7.26 (8H, m, ArH), 7.23-7.19 (2H, m, ArH), 5.76 (1H, t, J ) 5.5 Hz,
NHsCH2CH2), 5.71 (1H, s, (CH3)3CsNH), 4.96 (2H, m, NHs
CHCH3), 3.22 (2H, d, J ) 16 Hz, NCH(H)sCO), 3.18 (2H, d, J ) 16
Hz, NCH(H)sCO), 3.07 (2H, dt, J ) 6.1, 6.1 Hz, NHCH2CH2), 2.53
(2H, t, J ) 6.1 Hz, NHCH2CH2), 1.37 (6H, d, J ) 7.0 Hz, CHCH3),
1.21 (9H, s, (CH3)3C); 13C NMR (500 MHz, CDCl3) δ 170.0, 158.0,
143.4, 128.6, 127.3, 126.1, 59.1, 56.8, 50.3, 48.5, 37.9, 29.5, 21.8; FTIR
Potassium {tris[(N′-tert-butylureayl)-N-ethyl]aminato(hydroxo)-
cobaltate(III)} K[CoIIIH2 buea(OH)]. A solution of H6buea (105.0
mg, 0.237 mmol) in 5 mL of anhydrous DMA was treated with solid
KH (29.3 mg, 0.730 mmol) under an Ar atmosphere. The mixture was
stirred until gas evolution was completed. Co(OAc)2 (42.6 mg, 0.241
mmol) was added to the pale yellow solution, and stirring was continued
for 30 min. The mixture was filtered to remove KOAc (43.0 mg, 92%),
the dark blue filtrate was treated with dry dioxygen (3.3 mL, 0.13 mmol,
T ) 293.7 K, P ) 0.98 atm), and the resulting red solution was stirred
for 1 h. The solution was filtered, and a red solid was obtained after
vapor diffusion of Et2O into the filtrate. The solid was washed with
Et2O and dried under a vacuum to afford the product in 78% yield
(103 mg). The spectroscopic properties of the complex [CoIIIH3-
buea(OH)]- matched those previously described for the complex
prepared from water.5a,d
K[CoIIIH22iPr(18OH)] from 18O2. A solution of the ligand H52iPr (100
mg, 0.250 mmol) dissolved in 4 mL of anhydrous DMA was treated
with solid KH (30 mg, 0.75 mmol). The mixture was stirred until gas
evolution ceased. Co(OAc)2 (44 mg, 0.25 mmol) was added to the pale
yellow solution, and stirring was continued for 30 min. The aqua blue
mixture was treated with 18O2 (3.4 mL, 0.14 mmol at T ) 293.5 K,
P ) 0.99 atm), and the resulting mixture stirred for 1 h. The mixture
was placed under a vacuum for a few minutes to remove any unreacted
18O2. KOAc was then removed by filtration, and the filtrate was con-
centrated in vacuo. Treatment of the residue with Et2O produced a dark
(Nujol) 3284 (NsH), 1645 (CdO); [R]20 -40.8 (c 0.250, CHCl3);
D
HRMS (ES+): Exact mass calcd for C27H40N5O3 [M + H], 482.3131.
Found 482.3132.
Potassium {Bis[(N′-tert-butylureayl)-N-ethyl]-(N′′-isopropylcarba-
moylmethyl)-aminato-cobaltate(II)} K[CoIIH22iPr]. A solution of the
ligand H52iPr (150 mg, 0.374 mmol) dissolved in 6 mL of anhydrous
DMA was treated with solid KH (45 mg, 1.1 mmol). The mixture was
stirred until gas evolution ceased. Co(OAc)2 (66 mg, 0.37 mmol) was
added to the pale yellow solution, and stirring was continued for 30
min. The blue mixture was filtered to remove KOAc (74 mg, 100%),
which was washed with DMA. Vapor diffusion of Et2O into the filtrate
produced aqua blue crystals, which were filtered, washed with Et2O,
and dried under a vacuum to 173 mg (79%). Anal. Calcd (found) for
K[CoIIH22iPr]‚DMA, C23H46CoKN7O4: C, 47.41 (47.29); H, 7.96 (8.14);
N, 16.83 (17.14); FTIR (Nujol, cm-1) ν(NH) 3400, ν(CO) 1658, 1610,
1588, 1572; λmax (DMA, nm (ꢀ, M-1 cm-1)) 388 (34), 594 (160), 614
(sh); X-band EPR (DMA, 4 K) g ) 4.0, 2.0.
Potassium {bis[(N′-tert-butylureayl)-N-ethyl]-(N′′-isopropylcarba-
moylmethyl)-aminato-cobaltate(II)} K[CoIIH1iPr] was prepared fol-
lowing the procedure outlined for K[CoIIH22iPr] using H41iPr (200 mg,
0.559 mmol), 8 mL of anhydrous DMA, KH (67 mg, 1.7 mmol), and
9
15480 J. AM. CHEM. SOC. VOL. 128, NO. 48, 2006

Regulating Secondary Coordination Sphere of Metal Ions
A R T I C L E S
Table 1. Crystallographic Data for K[CoIIH20iPr]‚DMA, K[CoIIH1iPr]‚0.5DMA‚0.25Et2O‚0.25H2O, and K[CoIIH22iPr]‚Et2O
K[CoIIH1iPr
0.25Et2O
]
‚
0.5DMA
‚
salt
K[CoIIH20iPr
]
‚
DMA
‚
0.25H2O
K[CoIIH22iPr
]‚Et2O
molecular formula
fw
T (K)
C19H36CoKN5O4
496.56
100(2)
C20H39.5CoKN5.5O4
519.10
100(2)
C23H47CoKN6O4
569.70
100(2)
space group
a (Å)
b (Å)
P1
P1h
Pna21
12.768(4)
14.914(5)
15.3777(4)
115.77(8)
102.215(8)
101.032(8)
4 (Z′ ) 2)
2434(1)
1.352
10.918(2)
16.900(4)
29.431(6)
88.622(6)
83.727(5)
86.822(6)
8 (Z′ ) 4)
5389(2)
1.280
21.116(4)
10.467(2)
26.338(5)
90
90
90
8 (Z′ ) 2)
5821.3(19)
1.300
0.0602
0.1530
1.012
c (Å)
R (deg)
â (deg)
γ (deg)
Z
V (Å3)
δ
calcd (Mg/m3)
Ra
0.0357
0.0986
1.003
0.0900
0.2661
1.001
b
Rw
GOFc
2
2
2
a R ) [∑|∆F|/∑|Fo|]. b Rw ) {∑[ω(Fo - Fc )2]/∑[ω(Fo )2]}1/2
.
c Goodness of fit on F2.
red solid that was filtered, washed with Et2O, and dried under a vacuum
Crystallography. General Methods. Intensity data for the com-
pounds were collected using a Bruker APEX CCD area detector13
mounted on a Bruker D8 goniometer using graphite-monochromated
Mo KR radiation (λ ) 0.710 73 Å). The data were collected at 100(2)
K. For each structure, intensity data were measured as a series of ω
oscillation frames: for K[CoH22iPr]‚C4H10O data were collected at 0.3°
for 15 s/frame; for K[CoIIH1iPr]‚(C4H10O)0.25‚(C4H9NO)0.50‚(H2O)0.25 and
[Et4N]2[CoII0(CN)] data were collected for 60 s/frame; and for K[CoII0]‚
DMA data were obtained for 5 s/frame. The structures were solved by
direct methods and refined by full-matrix least-squares methods on F2.14
Hydrogen atom positions were initially determined by geometry and
refined by a riding model. Non-hydrogen atoms were refined with
anisotropic displacement parameters. Hydrogen atom displacement
parameters were set to 1.2 (1.5 for methyl groups) times the displace-
ment parameters of the bonded atoms. The displacement ellipsoids are
drawn at the 50% probability level. The data were corrected for
absorption by the semiempirical method.15 Space groups were deter-
mined by statistical methods and verified by subsequent refinement.
Partial crystallographic data are presented in Table 1. Full refinement
parameters can be found in the CIFs that are included in the Supporting
Information.
to 103 mg (82%). FTIR (Nujol, cm-1) ν(18OH) 3651.
[Bu4N][CoIIIH3buea(18OH)] from 18O2. A solution of [Bu4N][CoIIH3-
buea] (50 mg, 0.074 mmol) in 10 mL of CH3CN was treated with 18O2
(1.3 mL, 0.037 mmol at T ) 295.5 K, P ) 0.98 atm), and the resulting
mixture stirred for 1 h. The mixture was placed under a vacuum, the
volume was reduced to ∼3 mL, and diethyl ether was added until a
dark red precipitate appeared. The solid was separated via filtration,
washed with diethyl ether, and dried (46 mg, 90%).
Tetraethylammonium {Tris[(N′-tert-butylureayl)-N-ethyl]aminato-
(cyano)cobaltate(II)} [Et4N]2[CoIIH2OiPr(CN)]. A solution of K[CoII0]‚
DMA (51 mg, 0.103 mmol) in 3 mL of DMA was treated with Et4-
NCN (18.9 mg, 1.114 mmol) under an argon atmosphere. The blue
solution immediately turned violet and was stirred for 1 h. The solution
was filtered, and vapor diffusion of Et2O into the filtrate produced a
mixture of violet crystals and a violet amorphous solid. A crystal was
chosen and analyzed by X-ray diffraction. Repeated attempts to obtain
a satisfactory element analysis were unsuccessful. FTIR (Nujol, cm-1
)
2089, 1553, 1250, 1131, 1005; λmax (DMA) 541 nm; X-band EPR
(DMA, 77 K) g ) 4.0
Physical Methods. NMR spectra were recorded on Bruker Avance
400 and 500 MHz spectrometers equipped with Silicon Graphics
workstations. Mass spectra were obtained on either a VG ZAB high-
resolution double-focusing instrument or a VG Autospec-Q tandem
hybrid of EBEqQ configuration. Electronic spectra were recorded with
a Cary 50 spectrophotometer using a 1.00 mm quartz cuvette. FTIR
spectra were collected on a Mattson Genesis series FTIR instrument
with values reported in wavenumbers. Perpendicular-mode X-band EPR
spectra were collected using a Bruker EMX spectrometer equipped with
an ER041XG microwave bridge. Spectra for EPR samples were
collected using the following spectrometer settings: attenuation ) 25
dB, microwave power ) 0.638 mW, frequency ) 9.47 GHz, sweep
width ) 5000 G, modulation amplitude ) 10.02 G, gain ) 1.00 ×
103, conversion time ) 81.920 ms, time constant ) 655.36 ms, and
resolution ) 1024 points. Low-temperature (4 K) spectra were obtained
using an Oxford Instrument liquid He quartz cryostat. Cyclic voltam-
metric experiments were conducted using a BAS CV 50W (Bioana-
lytical Systems Inc., West Lafayette, IN) voltammetric analyzer
following methods previously described.11d A 1.0 mm glassy carbon
electrode was used as the working electrode to measure the cyclic
voltammograms (CV) at scan velocities between 0.1 and 1.0 V‚s-1. A
ferrocinium/ferrocene couple ([Cp2Fe]+/0) was used to monitor the
reference electrode (Ag+/Ag) and was observed at E1/2 ) 0.050 V with
∆Ep ) 0.10 V and ipa‚ipc-1 ) 0.85 at an ν ) 0.1 V‚s-1 in DMF under
ambient temperature.
K[CoH22iPr]‚C4H10O crystallized in the orthorhombic space group
Pna21 with cell parameters determined from a nonlinear least-squares
fit of 9757 peaks in the range 2.30° < θ < 26.00°. A total of 48 815
data were measured in the range 1.93° < θ < 26.00°. Minimum and
maximum transmission factors of 0.8368 and 0.8867 were used in the
adsorption correction. This structure contains two formula units per
asymmetric unit. The solvent molecules were significantly disordered
and modeled using the Squeeze program.16 The Flack parameter
indicated that the sample suffered from some inversion twinning. A
total of 542 parameters were refined against one space group restraint
and 11 400 data to give wR(F2) ) 0.1530 and S ) 1.012 for weights
of w ) 1/[σ2(F2) + (0.1160P)2], where P ) [Fo + 2Fc2]/3. The final
2
R(F) was 0.0602 for the 9926 observed, [F > 4σ(F)], data. The largest
shift/s.u. was 0.001 in the final refinement cycle. The final difference
map had maxima and minima of 1.908 and -0.478 e/Å3, respectively.
The absolute structure was determined by refinement of the Flack
(13) (a) Data Collection: SMART Software Reference Manual; Bruker-AXS:
Madison, WI, 1994. (b) Data Reduction: SAINT Software Reference
Manual; Bruker-AXS: Madison, WI, 1995.
(14) (a) Sheldrick, G. M. SHELXTL Version 5 Reference Manual; Bruker-
AXS: Madison, WI, 1994. (b) International Tables for Crystallography;
Kluwer Academic Publishers: Norwell, MA, 1995; Vol. C.
(15) Sheldrick, G. M. SADABS: Program for Empirical Absorption Correction
of Area Detector Data; University of Go¨ttingen: Germany, 2000.
(16) van der Sluis, P.; Spek, A. L. Acta Crystallogr., Sect. A 1990, 46, 194-
201.
9
J. AM. CHEM. SOC. VOL. 128, NO. 48, 2006 15481

A R T I C L E S
Lucas et al.
Scheme 1 a
parameter.17 The polar axis restraints were taken from Flack and
Schwarzenbach.18
K[CoH1iPr]‚(C4H10O)0.25‚(C4H9NO)0.50‚(H2O)0.25 crystallized in the
triclinic space group P1h, with cell parameters determined from a
nonlinear least-squares fit of 3874 peaks in the range 2.18° < θ <
26.00°. The first 50 frames were repeated at the end of data collection
and yielded a total of 136 peaks showing a variation of -0.04% during
the data collection. A total of 33 998 data were measured in the range
1.86° < θ < 26.00°. Minimum and maximum transmission factors of
0.7339 and 0.9446 were used in the adsorption correction. A total of
1338 parameters were refined against 659 restraints and 20 403 data
to give wR(F2) ) 0.2661 and S ) 1.001 for weights of w ) 1/[σ2(F2)
+ (0.1400P)2], where P ) [Fo2 + 2Fc2]/3. The final R(F) was 0.0900
for the 10 378 observed, [F > 4σ(F)], data. The largest shift/s.u. was
0.010 in the final refinement cycle. The final difference map had
maxima and minima of 1.246 and -0.731 e/Å3, respectively. There
were four cations and anions, two sites of DMA solvent, two sites of
diethyl ether (both near crystallographic centers of symmetry), and one
water molecule per asymmetric unit. Three of the anions contained
regions of disorder and were modeled in two orientations. The occu-
pancies for O(1A), N(3A), C(9A)-C(12A) refined to 0.613(15) and
0.387(15). The occupancies for C(15B)-C(17B) refined to 0.607(19)
and 0.393(19). The occupancies for C(15D)-C(17D) refined to 0.519-
(8) and 0.481(8). The DMA molecule, E, was disordered and modeled
in two orientations with occupancies of 0.590(12) and 0.410(12).
Restraints on the positional and displacement parameters of the
disordered atoms were required.
a Conditions: (a) ButNH2, Et2O, 0 °C to rt, 86%; (b) ButNCO, NaHCO3,
THF, 81%; (c) potassium phthalimide, DMF, 120 °C, 73%; (d) H2NNH2‚H2O,
EtOH, ∆, >98%; (e) BnNH2, Et3N, NaI, THF, ∆, 77%; (f) cyclohexene,
10% Pd/C, MeOH, ∆, 86%.
sitates having metal complexes with similar primary coordina-
tion spheres but variable H-bond arrangements in their secondary
coordination environments. Such metal complexes can be gener-
ated from an appropriate series of ligands whose design takes
into account both coordination spheres. The modular nature of
the syntheses of tripodal compounds provides the opportunity
to make changes in ligand structures via manipulation of the
functional groups within each arm of the tripod.19
We previously have shown that the urea-based tripodal ligand
[H3buea]3- provides a network of three H-bond donors around
a metal ion,5 while carboxamide-based ligands such as [0R]3-
provide none.11 The intermediate members of the series with
0-3 H-bond donors and highly anionic primary coordination
environments can be obtained by preparing hybrids of these
parent ligands (Figure 1). Besides varying the H-bond network
around a metal ion, these hybrids can also be used to influence
the overall cavity architecture through the choice of the R groups
attached to the carboxamide arms.
K[CoII0]‚DMA crystallized in the triclinic space group P1, with cell
parameters determined from nonlinear least-squares fits to 6234 peaks
in the range 2.34° < θ < 26.00°. A total of 21 098 data were collected
in the range 2.34° < θ < 26.00°. Minimum and maximum transmission
factors of 0.690 and 0.855 were used in the adsorption correction. There
were two formula units per asymmetric unit of the cell. Both solvent
molecules were disordered and were modeled in two orientations. The
occupancies of the solvent molecules refined to S: 0.656(3) and 0.344-
(3); T: 0.852(3) and 0.148(3) for the unprimed and primed atoms.
Restraints on the positional and displacement parameters of the solvent
atoms were required. A total of 639 parameters were refined against
432 restraints and 4533 data to give wR(F2) ) 0.0986 and S ) 1.003
for weights of w ) 1/σ2(F2) + (0.0600P)2 + 1.6600P], where P )
2
[Fo + 2Fc2]/3. The final R(F) was 0.0357 for the 8553 observed,
[F > 4σ(F)], data. The largest shift/s.u. was 0.014 in the final refinement
cycle. The final difference map had maxima and minima of 0.987 and
-0.782 e/A3.
To synthesize the hybrid ligands we adopted a convergent
synthetic strategy by which the urea “arms” would be installed
on the amine nitrogen atom that would ultimately become the
apical nitrogen donor of the tripodal ligand. Ligands containing
two urea arms, thus two H-bond donors, would come from
alkyating the secondary amine 7 (Scheme 1) with an N-
alkylbromoacetamide (eq 1). The primary amine 5 could be
[Et4N]2[CoII0(CN)] crystallized in the triclinic space group P21/n
with cell parameters determined from nonlinear least-squares fit of 4395
peaks in the range 2.27° < θ < 26.00°. A total of 17 218 data were
measured in the range 2.05° < θ < 23.26°. Minimum and maximum
transmission factors of 0.836 and 0.986 were used in the adsorption
correction. The intensity date were truncated at 0.9 Å resolution because
data in the high resolution shells had R(int) > 0.25. The solvent was
badly disordered. The best model for the solvent was determined using
the Squeeze program.16 A total of 388 parameters were refined against
5756 data to give wR(F2) ) 0.2064 and S ) 1.075 for weights of w )
2
1/σ2(F2) + (0.0940P)2 + 13.0000P], where P ) [Fo + 2Fc2]/3. The
final R(F) was 0.0783 for the 4301 observed, [F > 4σ(F)], data. The
largest shift/s.u. was 0.000 in the final refinement cycle. The final
difference map had maxima and minima of 1.054 and -0.763 e/A3.
Results and Discussion
alkylated in a similar fashion with 2 equiv of an N-alkylbromo-
acetamide to give the tripodal ligands with a single H-bond
donating ureayl arm. Both of these amines would be derived
Design Considerations and Ligand Syntheses. Exploring
the regulatory effects of H-bonds on metal ion reactivity neces-
(17) Flack, H. D. Acta Crystallogr., Sect A 1983, 39, 876-881.
(18) Flack, H. D.; Schwarzenbach, D. Acta Crystallogr., Sect. A 1988, 44, 499-
(19) Bellemin-Laponnaz, S.; Gade, L. H. Angew. Chem., Int. Ed. 2002, 41,
3473-3475.
506.
9
15482 J. AM. CHEM. SOC. VOL. 128, NO. 48, 2006

Regulating Secondary Coordination Sphere of Metal Ions
A R T I C L E S
Scheme 2 a
from the common intermediate 1-tert-butyl-3-(2-chloroethyl)-
urea (3).
Acylation of the commercially available starting compound
2-chloroethylamine hydrochloride with tert-butyl isocyanate
afforded 3 in 81% yield following recrystallization from Et2O
(Scheme 1). Alternatively, 3 was prepared from 2-chloroethyl
isocyanate and tert-butylamine in 86% yield. This compound
(2 equiv) was used to alkylate benzylamine, producing the
N-benzyl tertiary amine 6 in 77% yield. Our initial attempts to
debenzylate by catalytic transfer hydrogenolysis using ammo-
nium formate20 resulted in clean and efficient cleavage of the
benzyl group as indicated by TLC and 1H NMR spectroscopy.
However, the similar solubility properties of the product 7 and
ammonium formate made purification difficult and usually
incomplete. By replacing ammonium formate with cyclo-
hexene21 as the hydrogen atom source, debenzylation was
accomplished with pure product obtained in 86% yield.
Preparation of the primary amine 5 needed for ligands con-
taining only one H-bond donor made use of the Gabriel amine
synthesis.22 Chloroethylurea 3 was converted to the phthalimi-
dourea 4 using potassium phthalimide in DMF. The product
was obtained in 73% yield following recrystallization of the
crude product from acetone-hexane. Hydrazinolysis of 4 under
standard conditions with hydrazine monohydrate in refluxing
EtOH provided the desired primary amine 5 in greater than 98%
yield.23 Amine 5 was isolated as a hygroscopic white solid that
turns to a pale yellow oil upon standing under ambient
conditions.
The amide arms of the unsymmetrical ligands are derived
from N-alkylbromoacetamide derivatives 8-11.24 We prepared
three compounds in high yields from bromoacetyl bromide and
2 equiv of a primary amine in CH2Cl2: isopropyl (85%), cyclo-
pentyl (87%), and (S)-R-methylbenzyl (98%) (eq 1). The choice
of these R groups was based on their use in the previously
prepared symmetrical carboxamide-based compound, H30R.11
Amine 6 was used for the preparation of compounds with a
single H-bond donor. Alkylating this amine with 2 equiv of
N-alkylbromoacetamides 8-11 produced compounds H41R
(Scheme 2). These reactions were done in THF with Et3N as
base and employed the use of catalytic amounts of NaI. Com-
pounds H41R were prepared in yields ranging from 56 to 80%.
Similarily, ligands with two H-bond donors were prepared by
reacting amine 7 with N-alkylbromoacetamides 8-11 (Scheme
2). These reactions were carried out in the presence of Et3N in
refluxing THF. Yields for these reactions, which resulted in H52R
containing one carboxamide and two urea groups, ranged from
58 to 75%.
a Conditions: (a) 8-10, Et3N, THF, NaI (cat.), ∆; (b) 8-10, Et3N,
THF, ∆.
(equiv) of KH under an argon atmosphere to produce the ligands
[H22iPr]3-, [H1iPr]3-, and [0iPr]3- (Scheme 3). The addition of
solid Co(OAc)2 produced a blue solution and a white precipitate
(KOAc, 2 equiv). The potassium salts of [CoIIH22iPr]-,
[CoIIH1iPr]-, and [CoII0iPr]- were isolated in greater than 75%
yield after recrystallization from DMA (or DMF)-diethyl ether
and were stable for weeks when stored in a dry, anaerobic
environment.
Single-crystal X-ray diffraction investigations on K[CoIIH22iPr],
K[CoIIH1iPr], and K[CoII0iPr]- confirm that the cobalt(II) centers
have similar primary coordination spheres. Table 2 summarizes
selected distances and angles for each structure, and Figure 2
shows the thermal ellipsoid diagrams for [CoIIH22iPr]-,
[CoIIH1iPr]-, and [CoII0iPr]-. Single crystals of [CoIIH22iPr]- and
[CoII0iPr]- contained two crystallographically independent, but
chemically equivalent, anions in the asymmetric unit; [CoIIH1]-
had four independent anions, of which three contained regions
of disorder. Selected metrical data for each complex are pre-
sented in Table 2 as average values.
Examination of the molecular structures reveals that each
complex is four-coordinate with a trigonal monopyramidal
(TMP) geometry. The trigonal planes of the complexes are
defined by the deprotonated urea/amide nitrogen atoms, with
the amino nitrogen atom N1 as the apical donor, which is
positioned nearly perpendicular to the trigonal plane. The three
Co(II) complexes have similar metrical parameters; for instance,
the average Co1-N1 distance for [CoII0iPr]- is 2.059(2) Å, while
[CoIIH1iPr]- and [CoIIH22iPr]- have values of 2.070(7) Å and
2.073(4) Å, respectively. In [CoIIH22iPr]- and [CoIIH1iPr]- the
Co-Nurea and Co-Namidate bond distances are statistically
equivalent, with average distances of 1.945(3) Å and 1.948(7)
Å, respectively. The Co-Namidate bond lengths in [CoII0iPr]- are
slightly longer, with an average bond distance of 1.967(2) Å.
This value is nearly the same as the 1.972(2) Å bond lengths
observed previously in [CoII0But]-.11d
The X-ray structural results demonstrate that the tripodal
ligands in complexes [CoIIH22iPr]-, [CoIIH1iPr]-, and [CoII0iPr]-
bind in similar ways, which is further illustrated by the structural
overlays shown in Figure 3. The depictions include only the
metal-binding sites of the three complexes and confirms that
the primary coordination spheres around the Co(II) centers are
nearly identical. The similarities in structure are indicated by a
root-mean square value of 0.07 Å.
Preparation and Molecular Structures of [CoIIH22iPr]-,
[CoIIH1iPr]-, and [CoII0iPr]-. This series of Co(II) complexes
was made to examine how the ligand influences the chemistry
of metal ions. Ligands [H22iPr]3-, [H1iPr]3-, and [0iPr]3- were
targeted because we showed previously that tri(carboxamide)
tripods with appended isopropyl groups provided suitable
cavities for exogenous ligand binding.11b,c,25 The complexes were
prepared by deprotonating H52iPr, H41iPr, and H30iPr with 3 equiv
(20) Adger, B. M.; O’Farrell, C.; Lewis, N. J.; Mitchell, M. B. Synthesis 53-
55.
(21) Overman, L. E.; Mendelson, L. T.; Jacobsen, E. J. J. Am. Chem. Soc. 1983,
105, 6629-6637.
(22) Gabriel, S. Ber. Dtsch. Chem. Ges. 1887, 20, 2224-2236.
(23) Ing, H. R.; Manske, R. H. F. J. Chem. Soc. 1926, 2348-2351.
(24) Weaver, W. E.; Whaley, W. M. J. Am. Chem. Soc. 1947, 69, 515-516.
9
J. AM. CHEM. SOC. VOL. 128, NO. 48, 2006 15483

A R T I C L E S
Scheme 3
Lucas et al.
Table 2. Selected Bond Distances and Angles for [CoIIH22iPr]-,
and occurs to minimize the steric interactions between the
isopropyl and carbonyl groups of each amide moiety.11b,c
[CoIIH1iPr]-, and [CoII0iPr - a
]
distances (Å) or
angles (deg)
Spectroscopic Properties of [CoIIH22iPr]-, [CoIIH1iPr]-, and
[CoII0iPr]-. The electronic absorbance spectra for the three
complexes measured in DMA are shown in Figure 4A. The
spectra are characterized by three general bands at λmax ∼390,
590, and 610 nm with extinction coefficients of less than 200
M-1 cm-1. Each spectrum also contains a broad shoulder at
λmax = 700 nm. These spectral properties agree with those
reported previously for Co(II) complexes with TMP geometry,11d
suggesting that the cavities remain unoccupied in solution. The
electron paramagnetic resonance (EPR) spectra of [CoIIH22iPr]-,
[CoIIH1iPr]-, and [CoII0iPr]- also resemble one another. The
X-band EPR spectra recorded as frozen DMA solutions at 4 K
are presented in Figure 4B. All three spectra have comparable
features at g-values of 4.0 and 2.0, which correspond to
-
-
-
[CoIIH22iPr
]
[CoIIH1iPr
]
[CoII0iPr
]
Co1-N1
2.073(4)
1.945(3)
1.946(3)
1.944(4)
87.1(1)
85.9(1)
85.9(1)
118.9(2)
125.2(1)
114.6(1)
2.070(7)
1.944(6)
1.956(8)
1.944(6)
87.0(3)
84.6(3)
85.9(3)
116.6(5)
121.1(3)
120.9(5)
2.059(2)
1.972(2)
1.962(2)
1.968(2)
84.91(7)
85.16(7)
84.75(7)
119.20(7)
120.57(7)
117.93(7)
Co1-N2
Co1-N3
Co1-N4
N1-Co1-N2
N1-Co1-N3
N1-Co1-N4
N2-Co1-N3
N2-Co1-N4
N3-Co1-N4
a There are two independent anions in the asymmetric units for
[CoIIH22iPr]-, [CoII0iPr - and four for [CoIIH1iPr]-. Metrical parameters are
]
reported as averages.
The molecular structures also reveal that the complexes have
different secondary coordination spheres. In [CoIIH22iPr]- and
[CoIIH1iPr]- the appended urea and isopropyl amidate groups
form the desired hybrid cavities, encompassing the vacant axial
coordination sites. In both complexes, the urea N-H vectors
are positioned within the cavity, proximal to the Co(II) centers.
For [CoIIH22iPr]-, two H-bond donors exist within the secondary
coordination sphere, whereas [CoIIH1iPr]- has only one. Note
also that the appended isopropyl groups of the amide function-
alities adopt conformations in which the methyl substituents
surround the metal centers and thus serve as scaffolds for the
cavity. Moreover, the methine hydrogen atoms face outward
from the cavity toward the carboxamide carbonyl groups. This
arrangement of the isopropyl groups is also observed in
[CoII0iPr]- and creates a cavity without H-bond donors. This
orientation of groups is found in other complexes of [0iPr]3-
3
complexes having S ) /2 states with axial symmetry. The
virtually identical optical and EPR properties of [CoIIH22iPr]-,
[CoIIH1iPr]-, and [CoII0iPr]- suggest that the three complexes
have comparable electronic structures, which undoubtedly
correlates with similar structures among their primary coordina-
tion spheres.
Electrochemical Properties of [CoIIH22iPr]-, [CoIIH1iPr]-,
and [CoII0iPr]-. Cyclic voltammetry (CV) was used to explore
the redox properties of the three CoII complexes in DMF. CV
experiments on [CoII0iPr]- show a quasi-reversible process at
E1/2 ) -252 mV vs [Cp2Fe]+/[Cp2Fe], which is assigned to
the CoIII/CoII couple. In contrast, the other complexes exhib-
ited only irreversible oxidation processes, making it difficult to
compare directly the redox properties within the series of
Co(II) species. Nevertheless, the anodic potential (Epa) for the
9
15484 J. AM. CHEM. SOC. VOL. 128, NO. 48, 2006

Regulating Secondary Coordination Sphere of Metal Ions
A R T I C L E S
Figure 2. Thermal ellipsoid plots and space-filling representations of [CoIIH22iPr
]
- (A), [CoIIH1iPr
]
- (B), and [CoII0iPr
]
- (C). Thermal ellipsoids are drawn
at the 50% probability level, and only urea hydrogen atoms are depicted.
the cobalt centers. For instance, the oxidized Co(III) species
would more likely bind additional ligands (i.e., solvent mol-
ecules), and the presence of intramolecular H-bond donors could
assist this process, leading to lowering of the oxidation
potentials.
Properties of [CoIIH3buea]-. The synthesis of [CoIIH3buea]-
followed the same route as the other three Co(II) complexes.
However, K[CoIIH3buea] cannot be redissolved after isolation,
which has prevented further characterizations of this salt. In
situ preparation of [CoIIH3buea]- in DMA produces solutions
that have properties resembling those of the other complexes.
For instance, the absorbance spectrum of [CoIIH3buea]- has
features at the same wavelengths observed for other complexes,
but with significantly lower molar absorbtivities values (Figure
4A). Moreover, the spectrum displays a broadness that is absent
in the other three spectra, suggesting the possibility that more
than one species may be present. The X-band EPR spectrum
for [CoIIH3buea]- generated in situ exhibits a broader axial
-
Figure 3. Overlap of the primary coordination spheres for [CoIIH22iPr
]
-
-
(red), [CoIIH1iPr
] ] (black).
(blue), and [CoII0iPr
complexes scales linearly with the number of urea groups in
the complex: [CoIIH22iPr]- (-385 mV), [CoIIH1iPr]- (-240 mV),
and [CoII0iPr]- (-155 mV). The trend in Epa suggests that
deprotonated ureas are more electron-donating than deprotonated
amides, which is consistent with urea groups having higher pKa
values. However, this factor alone may not be the only contrib-
utor; the complexes' different secondary coordination spheres
could also contribute to the observed differences in Epa. It is
known in metalloproteins that changes in the H-bond networks
around metal centers influence redox potentials.26 A similar
effect could be occurring in [CoIIH22iPr]-, [CoIIH1iPr]-, and
[CoII0iPr]-, which differ in the number of H-bond donors near
3
signal with g-values consistent with an S ) /2 spin system
(Figure 4B).
Reactivity with Dioxygen. [CoIIH3buea]- and [CoIIH22iPr]-.
We have explored the reactivity profiles of the four cobalt(II)
complexes with dioxygen. Spectroscopic and structural studies
show that [CoIIH22iPr]-, [CoIIH1iPr]-, and [CoII0iPr]- have similar
primary coordination spheres, but differing in their cavity struc-
tures surrounding the coordinately unsaturated metal centers.
Electrochemical results indicate some redox differences between
the complexes, but the oxidation potentials for the three
complexes are sufficiently negative so as to expect their ready
reaction with dioxygen.27 The data for [CoIIH3buea]- give an
uncertain picture of its structure(s) in solution, making direct
comparisons with the other complexes difficult; however, we
have included results of its reactivity toward dioxygen for
completeness.
(25) For examples of other amidate ligand systems, see: Margerum, D. W. Pure
Appl. Chem. 1983, 55, 23-34. (b) Collins, T. J. Acc. Chem. Res. 1994, 27,
279-285. (b) Collins, T. J. Acc. Chem. Res. 2002, 35, 782-790. (c) Collins,
T. J.; Kostka, K. L.; Mu¨nck, E.; Uffelman, E. S. J. Am. Chem. Soc. 1990,
112, 5637-5639. (d) Collins, T. J.; Fox, B. G.; Hu, Z. G.; Kostka, K. L.;
Mu¨nck, E.; Rickard, C. E. F.; Wright, L. J. J. Am. Chem. Soc. 1992, 114,
8724-8725. (e) Ghosh, A.; Tiago de Oliviera, F.; Yano, T.; Nishioka, T.;
Beach, E. S.; Kinoshita, I.; Mu¨nck, E.; Ryabov, A. D.; Horwitz, C. P.;
Collins, T. J. J. Am. Chem. Soc. 2005, 127, 2505-2513.
(26) Representative examples: (a) Vance, C. K.; Miller, A.-F. Biochemistry 2001,
40, 13079-13087. (b) Xie, J.; Yikilmaz, E.; Miller, A.-F.; Brunold, T. C.
J. Am. Chem. Soc. 2002, 124, 3769-3774.
(27) Sawyer, D. T.; Sobkowiak, A.; Roberts, J. L., Jr. Electrochemistry for
Chemists, 2nd ed.; Wiley-Interscience: New York, 1995; p 360.
9
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A R T I C L E S
Lucas et al.
Figure 4. Visible electron absorbance spectra measured in DMA at room temperature (A) and X-band EPR spectra of frozen DMA solutions recorded at
-
-
-
-
4 K (B): [CoIIH33iPr
] ] ] ] (;).
(‚‚‚), [CoIIH22iPr (s - - - s), [CoIIH1iPr (- - -), and [CoII0iPr
Scheme 4 a
Figure 5. FTIR spectra of [CoIIIH3buea(OH)]- (A) and [CoIIIH22iPr(OH)]-
(B). Dashed-line spectra are complexes derived from 16O2 and solid-lined
are those from 18O2.
a Conditions: (a) 3 KH, DMA, Ar, rt; (b) Co(OAc)2, DMA, Ar, rt; (c)
0.5 equiv of O2, DMA, rt.
Treating in situ prepared [CoIIH3buea]- in DMA with 0.5
equiv of O2 produced [CoIIIH3buea(OH)]- in 78% yield (Scheme
4). This complex has identical spectroscopic properties to those
of [CoIIIH3buea(OH)]- prepared from oxidation of [CoIIH3buea-
(OH)]2-, its CoII-OH analogue. Confirmation that dioxygen
was the source of the oxygen atom in the hydroxo ligand came
from isotopic labeling studies. We synthesized [CoIIIH3buea-
(18OH)]- following the same procedure as that shown in Scheme
4 using 18O2 as the oxidant. The solid-state FTIR spectrum of
[CoIIIH3buea(16OH)]- (Figure 5A) has a ν(O-H) band at 3589
cm-1 that shifts to 3579 cm-1 in [CoIIIH3buea(18OH)]- (ν(16-
OH)/ν(18OH) ) 1.003; calcd. 1.004). Another isotopically sensi-
tive band observed at ν ) 3621 cm-1 in [CoIIIH3buea(16OH)]-
appears at ν ) 3614 cm-1 in the 18O-isotopmer (ν(16OH)/ν(18-
OH) ) 1.002).
Figure 6. Visible electron absorbance spectra measured in DMA at room
temperature for [CoIIIH3buea(OH)]- (;) and [CoIIIH22iPr(OH)]- (- - -).
in [CoIIIH3buea(OH)]-, the ν(O-H) in [CoIIIH22iPr(OH)]-
appears at a higher frequency, consistent with a reduced number
of H-bond donors (and H-bonds) to the CoIII-OH unit. Note
also that the visible absorbance features in [CoIIIH22iPr(OH)]-
are nearly identical to those found for [CoIIIH3buea(OH)]-
(Figure 6).
Similar dioxygen reactivity was observed for [CoIIH22iPr]-.
Treating a DMA solution of [CoIIH22iPr]- with 0.55 equiv of
O2 afforded a red microcrystalline solid, whose analytical and
spectroscopic properties are consistent with the formulation
[CoIIIH22iPr(OH)]- (eq 2). For example, this complex has a
The reaction of [CoIIH3buea]- and [CoIIH22iPr]- with dioxy-
gen provides rare examples of O2 activation by CoII species,
for which reversible binding is the norm. Cobalt(II) complexes
have been shown in a few examples to activate dioxygen; most
of these are within the context of substrate oxidation processes
in which the identity of the reactive cobalt species is unknown.28
Several recent examples of dioxygen reactivity involving Co(I)
complexes have been reported, including the characterization
distinct FTIR peak at ν ) 3661 cm-1 assigned to the O-H
stretch (Figure 5B). This band moves to the expected frequency
(ν ) 3650 cm-1) in [CoIIIH22iPr(18OH)]-, again indicating that
the O-atom of the hydroxo ligand is derived from dioxygen
activation (vide supra). In comparison to the O-H vibration
(28) (a) Hanzlik, R. P.; Williamson, D. J. Am. Chem. Soc. 1976, 98, 6570-
6573. (b) Sobkowiak, A.; Sawyer, D. T. J. Am. Chem. Soc. 1991, 113,
9520-9523. (c) Punniyamurthy, T.; Bhatia, B.; Reddy, M. M.; Maikap,
G. C.; Iqbal, J. Tetrahedron 1997, 53, 7649-7670. (d) Jain, S. L.; Sain,
D. Angew. Chem., Int. Ed. 2003, 42, 1265-1267.
9
15486 J. AM. CHEM. SOC. VOL. 128, NO. 48, 2006

Regulating Secondary Coordination Sphere of Metal Ions
A R T I C L E S
Scheme 5
Figure 7. X-band EPR spectra recorded at 4 K for [CoIIH1iPr - (- - -) and
]
after treating with O2 for 60 s (;) (A); after treating the oxygenated sample
with argon (- - -) and after reintroducing O2 for 60 s (;) (B). A 10 mM
-
DMA solution of [CoIIH1iPr
]
was used.
of Co-η2-O2 adducts29 as well as a dimeric Co2(µ-1,2-O2)2
species.30 It is unclear if the reaction pathways leading to
[CoIIIH3buea(OH)]- and [CoIIIH22iPr(OH)]- proceed through
high valent intermediates with terminal oxo ligands, such as a
CoIV-oxo species;31 related species have been proposed for
dioxygen activation by iron and manganese complexes of the
[H3buea]3- ligand.5b,i,j
-
Figure 8. Visible electron absorbance spectra for [CoIIH1iPr
] after the
addition of O2 illustrating the production of [CoIIIH1iPr(OH)]- (A) and
monitoring the change of [CoIIIH1iPr(OH)]- over time (B). Spectra in A
and B were recorded at 1 and 25 min intervals, respectively.
[CoIIH1iPr]-. The dioxygen reactivity of [CoIIH1iPr]- is differ-
ent than the other two Co(II) complexes. Under similar condi-
tions used to prepare [CoIIIH3buea(OH)]- and [CoIIIH22iPr(OH)]-,
[CoIIH1iPr]- does not appear to form a Co(III)-OH complex.
Analysis of solutions prepared by treating a DMA solution of
[CoIIH1iPr]- with 0.5 equiv of O2 shows that nearly all of the
Co(II) starting compound is present (Scheme 5). Unreacted
[CoIIH1iPr]- remained even after its solution was stirred for 18 h,
with no indication of oxidation.
1
adduct, which is known to have S ) /2 ground states, is one
possible species that could give rise to the g ) 2 signal.32
Revision to a spectrum that is similar to, but less intense, than
that of [CoIIH1iPr]- was accomplished by purging the sample
with argon for 10 min (Figure 7B). Bubbling excess dioxygen
into the thawed sample for 15 min reproduced the spectrum
with the isotropic feature at g ) 2 but at a lower intensity
compared to the first cycle. These results are indicative of a
system with some capability of reversible O2 binding, which is
known for Co(II) species.33 However, the reversible process is
lost over time as the species producing the g ) 2.0 signal
appears to have limited stability in DMA solution at room tem-
perature. EPR spectra obtained periodically over the course of
24 h showed that the g ) 2.0 signal diminished substantially,
consistent with the results found for the O2 cycling experiments
shown in Figure 7.
The reaction was further investigated by bubbling an excess
of dioxygen into solutions of [CoIIH1iPr]- and analyzing for
cobalt-containing species (Scheme 5). In one set of experiments,
10 mM DMA solutions of [CoIIH1iPr]- in EPR tubes were
treated with excess dioxygen for 1 min. After addition was
completed, the samples were immediately frozen and analyzed
by EPR spectroscopy at 4 K. The peak corresponding to
[CoIIH1iPr]- at g ) 4.0 greatly diminished, and a new isotropic
signal at g ) 2 was observed (Figure 7A), suggesting a spin
Monitoring the reaction with absorbance spectroscopy gave
further insights into the dioxygen reactivity of [CoIIH1iPr]-.
Figure 8A shows UV-vis spectra taken during the initial 30
min after treating [CoIIH1iPr]- with excess dioxygen. The
decrease in the bands at λmax ) ∼300 and 600 nm associated
1
change to a species with an S ) /2 ground state. A Co-O2
(29) (a) Egan, J. W., Jr.; Haggerty, B. S.; Rheingold, A. L.; Sendlinger, S. C.;
Theopold, K. H. J. Am. Chem. Soc. 1990, 112, 2445-2446. (b) Reinaud,
O. M.; Theopold, K. H. J. Am. Chem. Soc. 1994, 116, 6979-6980. (c)
Cramer, C. J.; Tolman, W. B.; Theopold, K. H.; Rheingold, A. L. Proc.
Natl. Acad. Sci. U.S.A. 2003, 100, 3635-3640. (d) Hu, X.; Castro-
Rodriguez, I.; Meyer, K. J. Am. Chem. Soc. 2004, 126, 13464-13473.
(30) Reinaud, O. M.; Yap, G. P. A.; Rheingold, A. L.; Theopold, K. H. Angew,
Chem., Int. Ed. 1995, 34, 2051-2052.
(32) (a) Basolo, F.; Hoffman, B. M.; Ibers, J. A. Acc. Chem. Res. 1975, 8, 384-
392 and references therein. (b) Sharma, A.; Borovik, A. S. J. Am. Chem.
Soc. 2000, 122, 8646-8655.
(31) Cobalt(IV) species have been report; for examples, see: (a) Bower, B. K.;
Tennent, H. G. J. Am. Chem. Soc. 1972, 94, 2512-2514. (b) Byrne, E. K.
J. Am. Chem. Soc. 1987, 109, 1282-1283. (c) Vol’Pin, M. E.; Levitin, I.
Y.; Sigan, A. L.; Nikitaev, A. T. Organomet. Chem. 1985, 279, 263-280.
(d) Harmer, J.; Doorslaer, S. V.; Gromov, I.; Bro¨ring, M.; Jeschke, G.;
Schwieger, A. J. Phys. Chem. B 2002, 106, 2801-2811.
(33) (a) Jones, R. D.; Summerville, D. A.; Basolo, F. Chem. ReV. 1979, 79,
139-179 and references therein. (b) Niederhoffer, E. C.; Timmons, J. H.;
Martell, A. E. Chem. ReV. 1984, 84, 137-203. (c) Norman, J. A.; Pez, G.
P.; Roberts, D. A. In Oxygen Complexes and Oxygen ActiVation by
Transition Metal Metals; Martell, A. E., Sawyer, D. T., Eds.; Plenum
Press: New York, 1988; pp 107-127.
9
J. AM. CHEM. SOC. VOL. 128, NO. 48, 2006 15487

A R T I C L E S
Scheme 6
Lucas et al.
6 and confirms that the cyano ligand fits into the cavity formed
by the three appended isopropyl groups.
Stability of the CoIII-OH Complexes. We have also exam-
ined the stabilities of the three CoIII-OH complexes in DMA
at room temperature. As reported earlier, [CoIIIH3buea(OH)]-
is stable for days in both the solid state and solution, showing
no measurable loss of its signature absorbance features. In
contrast, the other two CoIII-OH complexes are less stable in
solution: [CoIIIH22iPr(OH)]- and [CoIIIH1iPr(OH)]- decay with
initial rate constants of 5.9 × 10-8 and 2.5 × 10-7 M min-1
,
respectively.36 The changes in the in situ generated CoIII-
OH complexes were observed spectrophotometrically, as shown
in Figure 8B for [CoIIIH1iPr(OH)]-. The bands at λmax ) 430
and 700 nm that are indicative of [CoIIIH1iPr(OH)]- diminish
with no noticeable appearance of new features. A similar change
was found for [CoIIIH22iPr(OH)]-. We have not yet determined
the identity of the metal-containing species that results from
these processes.
Effect of the Intramolecular H-Bonding Networks. The
three well-characterized trigonal monopyramidal CoII complexes
[CoIIH22iPr]-, [CoIIH1iPr]-, and [CoII0iPr]- have different levels
of reactivity toward dioxygen, despite their nearly identical
primary coordination spheres. As noted, there is a 0.23 V spread
in the oxidation potentials between the complexes that would
contribute to their observed reactions with O2. The strongest
reducing agent in the series, [CoIIH22iPr]-, reacts readily with
dioxygen to produce [CoIIIH22iPr(OH)]- in good yield, even
when using substoichiometric amounts of O2. [CoIIH1iPr]- has
an Epa that is 0.145 V more positive yet only binds dioxygen
when it is in excess. We have not observed dioxygen binding
to [CoII0iPr]- even though its Epa is only 0.085 V more positive
than that of [CoIIH1iPr]-.
with [CoIIH1iPr]- coincides with the appearance of new peaks
at λmax ) 430 and 700 nm. The final optical spectrum in Figure
8A closely resembles those of the CoIII-OH complexes
[CoIIIH22iPr(OH)]- and [CoIIIH3buea(OH)]- (Figure 6). Further
support for the formulation of this species as a CoIII-OH
complex comes from FTIR studies on solid samples obtained
via precipitation:34 the spectra contain a signal at ν ) 3633 cm-1
,
which is consistent with an O-H stretch. We have been unable
to obtain this putative [CoIIIH1iPr(OH)]- complex in pure form,
which has prevented definitive characterization. Note that the
CoIII-OH complexes have a spin of S ) 1 and thus are not
detected in perpendicular-mode X-band EPR spectroscopy.
The difference in redox potentials cannot alone account for
the observed O2 chemistry in these CoII complexes. We suggest
that the addition of the intramolecular H-bond networks within
the secondary coordination sphere assist in the binding of O2
that leads to activation of dioxygen and formation of the CoIII-
OH complexes. The importance of H-bonds in dioxygen binding
and activation is well documented in metalloproteins.37 For
instance, the removal of residues within the active sites that
H-bond to the Fe-O2 unit in hemoglobins causes a loss in
respiration.38 In addition, dioxygen affinity in hemoglobins has
been correlated with the H-bond network surrounding the iron
The observations just described provide some insights into a
possible mechanism for the reaction between dioxygen and
[CoIIH1]- (Scheme 5). A CoII-O2 species is initially formed
under conditions of excess dioxygen. While the CoII-O2 species
is observable, it is relatively unstable and ultimately becomes
a CoIII-OH species, which we propose is [CoIIIH1iPr(OH)]-.
The steps for this conversion are still not known. Moreover,
this system is complicated by the instability of [CoIIIH1iPr(OH)]-,
preventing us from obtaining it in pure form (vide infra).
[CoII0iPr]-. This Co(II) complex is unreactive toward dioxy-
gen under our experimental conditions (Scheme 6). Treating
[CoII0iPr]- with 0.5 equiv of dioxygen or excess O2 resulted in
no observable change in its spectroscopic properties. Moreover,
isolated samples after exposure to O2 had properties identical
to [CoII0iPr]-. The lack of dioxygen binding and reactivity is
not attributed to steric effects caused by constraints within the
secondary coordination sphere. We have previously found that
Fe(II) and Mn(II) complexes of [0iPr]3- readily bind external
ligands, including dioxygen.11e Furthermore, [CoII0iPr]- binds
a cyanide ion to form the five-coordinate Co(II)-cyano
complex, [CoII0iPr(CN)]2-. The molecular structure of [CoII0iPr-
(CN)]2- determined by X-ray diffraction35 is shown in Scheme
(35) (Et4N)2[CoH1iPr(CN)] crystallized with one diethyl ether solvate per mol-
ecule in the triclinic space group P21/n with the following cell constants:
a ) 11.738(3) Å, b ) 31.298(8) Å, and c ) 12.271(4) Å; R ) 90°, â )
116.695(5)°, and γ ) 90°; V ) 4038(2) Å3, Z ) 4; R ) 0.0783, Rw
)
0.2064 with a GOF(F2) ) 1.075. See Supporting Information for details.
(36) The initial rate constants for the decay of [CoIIIH22iPr(OH)]- and
[CoIIIH1iPr(OH)]- were measured on solutions prepared with isolated
complexes.
(37) Selected examples: (a) Holmes, M. A.; Stenkamp, R. E. J. Mol. Biol. 1991,
220, 723-737. (b) Fu¨lo¨p, V.; Phizackerley, R. P.; Soltis, S. M.; Clifton, I.
J.; Wakatuski, S.; Erman, J.; Hajdu, J.; Edwards, S. L. Structure 1994, 2,
201-208. (c) Mukai, M.; Nagano, S.; Tanaka, M.; Ishimori, K.; Morishima,
I.; Ogura, T.; Watanabe, Y.; Kitagawa, T. J. Am. Chem. Soc. 1997, 119,
1758-1766 and references therein; (d) Dunietz, B. D.; Beachy, M. D.;
Cao, Y.; Whittington, D. A.; Lippard, S. J.; Friesner, R. A. J. Am. Chem.
Soc. 2000, 122, 2828-2839. (e) Gherman, B. F.; Dunietz, B. D.;
Whittington, D. A.; Lippard, S. J.; Friesner, R. A. J. Am. Chem. Soc. 2001,
123, 3836-3837. (f) Du Bois, J.; Mizoguchi, T. J.; Lippard, S. J. Coord.
Chem. ReV. 2000, 200-202, 443-485. (g) Berglund, G. I.; Carlsson, G.
H.; Smith, A. T.; Szo¨ke, H.; Henriksen, A.; Hajdu, J. Nature 2002, 417,
463-468. (h) Tomchick, D. R.; Phan, P.; Cymborowski, M.; Minor, W.;
Holman, T. R. Biochemistry 2001, 40, 7509-7517.
-
(34) In a typical experiment, [CoIIH1iPr
]
(0.29 mmol) in 3 mL of DMA was
treated with excess dioxygen for 15 min, after which the reaction mixture
was placed under reduced pressure for 5 min. The resulting heterogeneous
mixture was filtered under argon, and the isolated solid was washed with
diethyl ether and dried in vacuo to afford a tan powder.
(38) Perutz, M. F.; Fermi, G.; Luisi, B.; Shaanan, B.; Liddington, R. C. Acc.
Chem. Res. 1987, 20, 309-321.
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Regulating Secondary Coordination Sphere of Metal Ions
A R T I C L E S
center.39 Similarly, protein dysfunction is observed in cyto-
chrome P450 when the active site H-bond network proximal to
the Fe-O2 moiety is disrupted.40
symmetrical carboxamide ligand [0iPr]3-, produce TMP Co(II)
complexes with nearly identical primary coordination spheres
and spectroscopic properties. In contrast, the complexes’
secondary coordination spheres differ because of the varied
structures formed around the cobalt ions by the tripodal ligands.
The combination of urea and isopropyl groups produces cavities
that place a different number of H-bond donors proximal to
the cobalt centers. These systems illustrate our approach for
producing site-specific modification of intramolecular H-bond
networks, which permit investigations into the role of H-bonds
in metal-mediated processes.
Our results strongly indicate that H-bond networks assist in
the dioxygen binding/activation by synthetic cobalt(II) com-
plexes. The importance of H-bonds in binding dioxygen to
transition metal complexes has been recognized for years as a
result of structural studies on myogoblin and hemoglobin
variants.4b,c,38,39 The cobalt complexes studied herein show that
binding4a and activation are also affected by the numbers of
H-bonds in the secondary sphere. The complexes with multiple
H-bond donors readily bind and activate dioxygen. Thus,
[CoIIH3buea]- and [CoIIH22iPr]- react with substoichiometric
amounts of dioxygen to produce [CoIIIH3bueaiPr(OH)]- and
[CoIIIH22iPr(OH)]-, their corresponding CoIII-OH derivatives,
in ∼ 75% yield. In contrast, [CoIIH1iPr]- only binds and reacts
with dioxygen under saturating conditions, whereas [CoII0iPr]-,
with no intramolecular H-bond donors, does not react with
dioxygen. Moreover, there is a correlation between the number
of intramolecular H-bonds and the stabilities of the CoIII-OH
complexes: the greater number of intramolecular H-bonds
produces the more stable complex. These findings highlight the
need to include secondary sphere effects in the design of
transition metal complexes. Moreover, they illustrate how well-
positioned H-bonds within the second sphere can impact metal-
related chemistry.
There is also a correlation between H-bonds and O2 binding/
activation observed by cobalt complexes described in this work.
[CoIIH22iPr]- and [CoIIH1iPr]- are able to form intramolecular
H-bonds in a Co-O2 adduct; [CoIIH22iPr]-, with two H-bond
donors, clearly reacts at lower O2 concentrations compared with
[CoIIH1iPr]-, which only has one H-bond donor. The additional
H-bond donor in [CoIIH22iPr]- would assist in dioxygen binding,
the essential first step in metal-mediated O2 activation. More-
over, [CoII0iPr]- does not bind dioxygen and is the only complex
in the series that is incapable of forming intramolecular H-bonds.
Properties of the secondary coordination sphere also affect
the stabilities of the CoIII-OH complexes, which are the Co-
based products isolated after dioxygen activation. In particular,
the number of H-bond donors within the cavity correlates with
the overall stabilities of these complexes. With its symmetrical
cavity containing three H-bond donors, [CoIIIH3buea(OH)]- is
stable for weeks in solution and can be crystallized, whereas
[CoIIIH1iPr(OH)]-, with one H-bond donor, only has limited
stability in solution. We propose that this effect is manifested
in two synergistic ways. First, the greater number of H-bonds
to the CoIII-OH unit would reduce the nucleophility of the
hydroxo ligand, rendering the complexes less likely to react with
external species. Second, the greater number of intramolecular
H-bonds would reinforce the cavity structure created by the urea
groups, producing a more constrained microenvironment. The
net result would be a more rigid cavity that limits access to the
CoIII-OH moiety.
Summary
We have described preparative routes to a new series of
hybrid tripodal ligands. Convergent syntheses were developed
having the potential to produce a variety of ligands containing
at least one urea arm. In the present study, urea/carboxamide
tripods were made in order to probe the effects of H-bonds on
the binding and activation of dioxygen by cobalt(II) complexes.
The hybrid ligands [H22iPr]3- and [H1iPr]3-, along with the
Acknowledgment. Acknowledgment is made to the NIH
(GM50781) for financial support of this work and the NSF
(CHE-0079282) for funding of the X-ray diffraction instrumen-
tation.
Supporting Information Available: Cyclic voltammograms
for the Co(II) complexes, data used for determining the initial
rate constant for the decay of the CoIII-OH complexes, and
crystallographic details for K[CoIIH20iPr]‚DMA, K[CoIIH1iPr]‚
0.5DMA‚0.25Et2O‚0.25H2O, K[CoIIH22iPr]‚Et2O, and (Et4N)2-
[CoH1iPr(CN)]‚Et2O. This material is available free of charge
via the Internet at http://pubs.acs.org.
(39) (a) Kloek, A. P.; Yang, J.; Mathews, F. S.; Goldberg, D. E. J. Biol. Chem.
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Huang, S.; Huang, J.; Kloek, A. P.; Goldberg, D. E.; Friedman, J. M. J.
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JA063935+
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