Copper(II) complexes of novel N-alkylated derivatives of cis,cis-1,3,5-triaminocyclohexane. 1. Preparation and structure

Article abstract of DOI:10.1021/ic000829e

Novel N,N′,N″-trialkylated derivatives of cis,cis-1,3,5-triaminocyclohexane (tach), designated tach-R₃, were prepared through alkylation of N-protected tach with subsequent acid deprotection, to afford N-methyl, N-ethyl, and N-n-propyl derivatives as their trihydrobromide salts. The tach-neopentyl₃ and tach-furan₃ derivatives were prepared by formation of the imine from tach and pivaldehyde or furan-2-carboxaldehyde, respectively, followed by reduction of the imine. Complexes [Cu(tach-R₃)Cl₂] (R = Me, Et, n-Pr, CH₂-2-thienyl, and CH₂-2-furanyl) were prepared from CuCl₂ in MeOH or MeOH-Et₂O solvent. Crystallographic characterization of [Cu(tach-Et₃)Br_0.8Cl_1.2] (Pnma, a = 8.2265(1) A, b = 12.5313(1) A, c = 15.3587(3) A, Z = 4) reveals a square-based pyramidal CuN₃X₂ coordination sphere in which one nitrogen donor occupies the apical position at a slightly longer distance (Cu-N = 2.218(5) A) than those of the basal nitrogens (Cu-N = 2.053(2) A). The solution-phase (pH 7.4 buffered and methanol) and solid-phase structures of [Cu(tach-R₃)Cl₂] have been studied extensively by EPR and visible-near-IR spectroscopies. The square-based pyramidal structure is retained in solution, according to correspondence of solution and solid-state data. In aqueous solution, halide is replaced by water, as indicated by the high-energy UV-vis spectral shifts and bonding parameters of [Cu(tach-Et₃)]²⁺(aq) derived from EPR data. The proposed aqueous-phase species, in the pH range 7.4 to 10.1, is [Cu(tach-Et₃)(H₂O)₂]²⁺. The complex [Cu(tach-Me₃)]²⁺(aq) does not appear to dimerize or form metal-hydroxo species at pH 7.4, in contrast to other Cu(II)-triamine complexes, e.g., [Cu(1,4,7-triazacyclononane)]²⁺ (aq) and [Cu(tach-H₃)]²⁺(aq) (the complex of unalkylated tach). This difference is attributed to the steric effect of the N-alkyl groups in the tach-R₃ series.

Full text of DOI:10.1021/ic000829e

Inorg. Chem. 2001, 40, 4167-4175
4167
Copper(II) Complexes of Novel N-Alkylated Derivatives of
cis,cis-1,3,5-Triaminocyclohexane. 1. Preparation and Structure
Gyungse Park,† Junlong Shao,† Frances H. Lu,‡ Robin D. Rogers,§ N. Dennis Chasteen,†
Martin W. Brechbiel,‡ and Roy P. Planalp*,†
Departments of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, and
The University of Alabama, Tuscaloosa, Alabama 35487, and Chemistry Section, Radiation Oncology
Branch, National Institutes of Health, Building 10, Room B3-B69, Bethesda, Maryland 20892
ReceiVed July 21, 2000
Novel N,N′,N′′-trialkylated derivatives of cis,cis-1,3,5-triaminocyclohexane (tach), designated tach-R3, were prepared
through alkylation of N-protected tach with subsequent acid deprotection, to afford N-methyl, N-ethyl, and N-n-
propyl derivatives as their trihydrobromide salts. The tach-neopentyl3 and tach-furan3 derivatives were prepared
by formation of the imine from tach and pivaldehyde or furan-2-carboxaldehyde, respectively, followed by reduction
of the imine. Complexes [Cu(tach-R3)Cl2] (R ) Me, Et, n-Pr, CH2-2-thienyl, and CH2-2-furanyl) were prepared
from CuCl2 in MeOH or MeOH-Et2O solvent. Crystallographic characterization of [Cu(tach-Et3)Br0.8Cl1.2] (Pnma,
a ) 8.2265(1) Å, b ) 12.5313(1) Å, c ) 15.3587(3) Å, Z ) 4) reveals a square-based pyramidal CuN3X2
coordination sphere in which one nitrogen donor occupies the apical position at a slightly longer distance (Cu-N
) 2.218(5) Å) than those of the basal nitrogens (Cu-N ) 2.053(2) Å). The solution-phase (pH 7.4 buffered and
methanol) and solid-phase structures of [Cu(tach-R3)Cl2] have been studied extensively by EPR and visible-
near-IR spectroscopies. The square-based pyramidal structure is retained in solution, according to correspondence
of solution and solid-state data. In aqueous solution, halide is replaced by water, as indicated by the high-energy
UV-vis spectral shifts and bonding parameters of [Cu(tach-Et3)]2+(aq) derived from EPR data. The proposed
aqueous-phase species, in the pH range 7.4 to 10.1, is [Cu(tach-Et3)(H2O)2]2+. The complex [Cu(tach-Me3)]2+
-
(aq) does not appear to dimerize or form metal-hydroxo species at pH 7.4, in contrast to other Cu(II)-triamine
complexes, e.g., [Cu(1,4,7-triazacyclononane)]2+ (aq) and [Cu(tach-H3)]2+(aq) (the complex of unalkylated tach).
This difference is attributed to the steric effect of the N-alkyl groups in the tach-R3 series.
Introduction
Many Cu(II) complexes are known to cleave phosphodiester
bonds and, to a lesser degree, amide bonds.8,9 Tridentate amine
Copper possesses a rich coordination chemistry that is
reflected in its many biological and synthetic roles.1-4 Copper
complexes catalyze many reactions, including hydrolysis, Di-
els-Alder, and redox reactions. Copper(II) complexes that can
catalyze hydrolysis reactions of phosphate and amide linkages
are interesting as synthetic polynucleotide or peptide cleavage
agents. Although metal-catalyzed polynucleotide and peptide
cleavage reactions have been known for some time,5,6 interest
is turning to complexes with more labile active sites, such as
those of Cu(II) and the lanthanides, that may achieve greater
substrate turnover.7
ligands have been generally effective supports of Cu(II), as they
allow several open metal coordination sites. Detailed mechanistic
studies of Cu(II)-[9]aneN3 ([9]aneN3 ) 1,4,7-triazacyclononane)
complexes by Burstyn et. al. have led to a number of insights
into these processes.7,10,11 Several other trinitrogen ligands,
whose copper complexes catalyze phosphate diester cleavage
and transesterification, have also received careful mechanistic
study.12-14 However, many details of these processes remain
unclear or contradictory, underscoring the complexity of the
chemistry involved.
We have initiated studies of the structure, electronic proper-
ties, and reactivity of a number of biologically relevant copper
complexes that serve as hydrolytic cleavage agents. It is
important to understand the solution coordination geometries
and electronic structures of metal complexes that are potentially
active species or precursors to such species. It is believed that
* Corresponding author. Phone: (603) 862-2471. Fax: (603) 862-4278.
E-mail: roy.planalp@unh.edu.
† University of New Hampshire.
‡ National Institutes of Health.
§ The University of Alabama.
(1) Cotton, F. A.; Wilkinson, G.; Murillo, C. A.; Bochmann, M. AdVanced
Inorganic Chemistry; Wiley: New York, 1999; pp 873 ff.
(2) Evans, D. A.; Barnes, D. M.; Johnson, J. S.; Lectka, T.; von Matt, P.;
Miller, S. J.; Murry, J. A.; Norcross, R. D.; Shaughnessy, E. A.;
Campos, K. R. J. Am. Chem. Soc. 1999, 121, 7582.
(3) Evans, D. A.; Miller, S. J.; Lectka, T.; von Matt, P. J. Am. Chem.
Soc. 1999, 121, 7559.
(4) Hathaway, B. Copper. In ComprehensiVe Coordination Chemistry;
Wilkinson, G., Gillard, R. D., McCleverty, J. A., Eds.; Pergamon:
London, 1987; Vol. 5, Chapter 53.4 ff.
(8) Reddy, K. V.; Jacobson, A. R.; Kung, J. I.; Sayre, L. M. Inorg. Chem.
1991, 30, 3520.
(9) Sayre, L. M.; Reddy, K. V.; Jacobson, A. R.; Tang, W. Inorg. Chem.
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(10) Deal, K. A.; Burstyn, J. N. Inorg. Chem. 1996, 35, 2792.
(11) Hegg, E. L.; Burstyn, J. N. J. Am. Chem. Soc. 1995, 117, 7015.
(12) Wahnon, D.; Hynes, R. C.; Chin, J. J. Chem. Soc., Chem. Commun.
1994, 1441.
(5) Gustafson, R. L.; Martell, A. E. J. Am. Chem. Soc. 1962, 84, 2309.
(6) Chin, J.; Banaszczyk, M.; Jubian, V.; Zou, X. J. Am. Chem. Soc. 1989,
111, 186.
(13) Itoh, T.; Hisada, H.; Sumiya, T.; Hosono, M.; Usui, Y.; Fujii, Y. J.
Chem. Soc., Chem. Commun. 1997, 677.
(14) Itoh, T.; Hisada, H.; Usui, Y.; Fujii, Y. Inorg. Chim. Acta 1998, 283,
51.
(7) Hegg, E. L.; Burstyn, J. N. Coord. Chem. ReV. 1998, 173, 133.
10.1021/ic000829e CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/07/2001

4168 Inorganic Chemistry, Vol. 40, No. 17, 2001
Park et al.
Chart 1
phosphate diesters and implications of the observed kinetics for
the mechanism of hydrolysis.
Experimental Section
Materials and Methods. Anhydrous grade MeOH was obtained
from Fisher Scientific. Et2O was distilled from Na/K. Anhydrous grade
DMSO and DMF were obtained from Aldrich. Dipropyl sulfate was
purchased from TCI America. All other reagents were from Aldrich,
Sigma, or Fluka. Tach‚3HBr,19 tach-thioph3,18 tach-Me3,20 and tach-
20
Et3 were prepared as previously reported. 63Cu was obtained from
Cambridge Isotope Laboratories.
1H and 13C NMR were obtained using a Varian Gemini 300
instrument or a Bruker AM360 instrument. Chemical shifts are reported
in ppm on the δ scale relative to TMS, TSP, or solvent. Proton chemical
shifts are annotated as follows: ppm (multiplicity, integral, coupling
constant (Hz)). Chemical ionization mass spectra (CI-MS) were obtained
on a Finnegan 3000 instrument. Fast atom bombardment (FAB-MS)
mass spectra were taken on a Extrel 4000. Elemental analysis was
performed by Atlantic Microlabs (Atlanta, GA) or by Galbraith
Laboratories (Knoxville, TN).
EPR and Visible-Near-IR Spectroscopy. X-band (9.15 GHz) EPR
spectra were measured on a laboratory assembled spectrometer equipped
with a Bruker ER 041 XK-H microwave bridge and a Varian TE102
cavity fitted with a liquid nitrogen Dewar insert as described else-
where.21 Q-band (35 GHz) spectra were measured on a Varian E-9
spectrometer. The E-110 Q-band microwave bridge was modified with
a Quinstar Technology QLN-3635-AA low noise microwave amplifier,
giving a ∼7-fold improvement in signal/noise ratio at -13 dB
microwave power attenuation. A 20 dB directional coupler was inserted
in the microwave circuit for counting the frequency. A 10 dB isolator
was placed between the EIP model 448 A frequency counter and the
coupler to eliminate feedback interference to the microwave bridge from
the counter. A fabricated ribbon-wound cylindrical TE011 cavity22
immersed in a stream of cold dinitrogen gas was employed for Q-band
measurements at 100 K. Samples were contained in calibrated 3 mm
i.d.-4 mm o.d. quartz sample tubes for X-band measurements on frozen
solutions at 77 K and in 1.3 mm i.d.-2.0 mm o.d. quartz capillary
tubing for Q-band measurements at 100 K. A quartz flat cell was used
for room-temperature measurements on aqueous solutions at X-band.
For accurate g-factor determinations, the X-band microwave frequency
was determined using a Hewlett-Packard model 5350A counter and
the field calibrated with either a MicroNow model 515 NMR gaussmeter
or a standard sample of Mn2+ in CaO (g ) 2.0011(1) with field
separations of 8.627(4), 25.881(4), and 43.113(4) mT between the MI
) (1/2, (3/2, and (5/2 pairs of lines, respectively).23 The CaO sample
was blended with a trace amount of coal (g ) 2.0035(1)) to give a
central g-mark in the EPR spectrum and sealed under vacuum.
Spectrometer settings for X-band frozen solutions were the following:
microwave power ) 5 mW; modulation amplitude ) 0.2 mT at 100
kHz; scan time ) 500 s; time constant ) 0.3 s; frequency ) 9.1500
GHz; scan range ) 100 mT. Room-temperature X-band spectra were
obtained with the following settings: microwave power ) 10 mW;
modulation amplitude ) 0.5 mT; scan time ) 1000 s; time constant )
1 s; scan range ) 100 mT; frequency ) 9.5284 GHz. The spectrometer
settings for Q-band spectra were the following: microwave power )
190 µW; modulation amplitude ) 0.2 mT; scan time ) 16 min; time
constant ) 1 s; scan range ) 200 mT; frequency ) 34.8 GHz.
Aqueous samples for frozen solution EPR measurements were
prepared in 50 mM Hepes buffer/glycerol, pH 7.4 solution (2:1 v:v),
or in 50 mM Caps buffer/glycerol, pH 10.1 (2:1 v:v). The spectra of
the complex [Cu(tach-Me3)Cl2] in 50 mM HEPES buffer and 50 mM
HEPES/glycerol (2:1 v/v) were identical, suggesting that coordination
of glycerol to Cu(II) does not occur in the mixed solvent. Ligand-field
spectra of 5 mM complex in analytical grade methanol or 50 mM
HEPES buffer, pH 7.4, were measured in 1 cm quartz cuvettes on a
Varian Cary-5 UV/vis/NIR spectrophotometer. Spectra of solid samples
the active species involve association of the substrate to one or
more Lewis acidic metal(s), followed by the addition of a
nucleophile, generally hydroxide although others have been
postulated.11 The formation of the active species from the
precursor generally involves the steps of replacement of
coordinated halide by water, followed by hydrolysis of the
resulting aqua compounds to form a coordinated hydroxo group
that acts as nucleophile for phosphate cleavage. Therefore, these
studies have the long-term goal of better understanding the
mechanism of hydrolysis for the purposes of developing more
effective hydrolysis agents.
In the present work, we focus on Cu(II) complexes of
N,N′,N′′-trialkyltach (tach ) cis,cis-1,3,5-triaminocyclohexane)
(Chart 1). We have observed that aqueous [Cu(tach-R3)X2] (X
) Cl, Br) cleaves p-nitrophenyl phosphate diesters with rates
that slightly exceed those of [Cu([9]aneN3)Cl2].15 We are
therefore exploring the interaction of Cu(II) with tach-R3 and
reactivity of the resulting complexes. Tach, in the closed
conformation, is known to bind a variety of metals in a facial
geometry,16-18 but relatively little is known concerning the
effects of the addition of N-alkyl groups on coordination
properties of tach. The properties of unalkylated tach (also
designated “tach-H3” to distinguish from tach-R3, where R *
H) have been studied by Fujii et al., who observed cleavage of
2,4-dinitrophenyl phosphate esters by complexes formed from
Cu(II) and tach-H3 in situ.14 We draw on our recent synthesis
of tach-H3 and tach-R3 to overcome limitations on the avail-
ability of the ligands.19,20
Herein we report the synthesis of an array of N-substituted-
tach-Cu(II)-dihalide complexes and corresponding new tach
ligands and the determination of their solid-state and solution
structures. We have analyzed the hydrolysis of these dihalides
and assigned a structure of the resulting aquo species. In the
following paper,15 we report their hydrolysis activity toward
(15) Deal, K. A.; Park, G.; Shao, J.; Chasteen, N. D.; Planalp, R. P.;
Brechbiel, M. W. Inorg. Chem. 2001, 4176.
(16) Lions, F.; Martin, K. V. J. Am. Chem. Soc. 1957, 79, 1572.
(17) Hegetschweiler, K.; Kradolfer, T.; Gramlich, V.; Hancock, R. D. Chem.
Eur. J. 1995, 1, 74.
(18) Ye, N.; Rogers, R. D.; Brechbiel, M. W.; Planalp, R. P. Polyhedron
1998, 17, 603.
(19) Bowen, T.; Planalp, R. P.; Brechbiel, M. W. Bioorg. Med. Chem. Lett.
1996, 6, 807.
(20) Park, G.; Lu, F. H.; Ye, N.; Brechbiel, M. W.; Torti, S. V.; Torti, F.
M.; Planalp, R. P. JBIC 1998, 3, 449.
(21) Yang, X.; Chasteen, N. D. Biophys. J. 1996, 71, 1587.
(22) Wang, W.; Chasteen, N. D. J. Magn. Reson. 1996, 116, 237.
(23) Shao, J.; Grady, J. K.; Chasteen, N. D. EPR Newslett. 1999, 10, 7.

Copper(II) Complexes of N-Alkylated Derivatives
Inorganic Chemistry, Vol. 40, No. 17, 2001 4169
were obtained on powders blended in a KBr pellet. Spectra gathered
linearly in wavelength were converted to a wavenumber scale and least-
squares fitted to a sum of Gaussian functions using the software program
Origin 6.0 (MicroCal, Inc.).
with NaOH (1.29 g, 32.2 mmol) to form a clear solution. Benzene
(150 mL) was added, and the water was removed by azeotropic
distillation with a Dean-Stark trap. Furfural (3.097 g, 32.25 mmol)
was added during this process and then continued for 12 h. After
cooling, the solution was decanted and rotary evaporated to an oil (3.36
g, 86%): 1H NMR (CDCl3) δ 8.17 (s, 1H), 7.520 (d, 1H, J ) 0.9),
6.74 (d, 1H, J ) 3.3), 6.48 (dd, 1H, J ) 3.3,1.8), 3.50 (tt, 1H, J )
11.4, 3.9), 2.07 (q, 1H, J ) 12.0), 1.91 (br d, 1H, J ) 12.0); 13C NMR
(CDCl3) δ 151.58, 148.30, 144.90, 114.46, 111.60, 66.53, 40.67; MS
(CI/NH3) 364 (M+ + 1). Anal. Calcd for C21H21N3O3; C, 72.59; H,
6.10; N, 12.10. Found: C, 72.41; H, 6.04; N, 11.98.
Ligand Syntheses.
N,N′,N′′-Tripropyl-1,3,5-cis,cis-triaminocyclohexane-N,N′,N′′-tri-
p-toluenesulfonyl Amide (tachTs3Pr3). 1,3,5-cis,cis-Triaminocyclo-
hexane-N,N′,N′′-tri-p-toluenesulfonyl amide20 (10.69 g, 18.09 mmol)
was dissolved in dry DMF (150 mL), cooled with an ice bath, and
NaH (87 mmol) was added. After H2 evolution had ceased, dipropyl
sulfate (36.4 g, 0.200 mmol) was added. The reaction mixture was then
heated to ca. 90 °C for 18 h. After cooling, concentrated NH4OH/H2O
(1:1) (150 mL) was added and the reaction was stirred for 1 h. The
solvents were removed by high-vacuum rotary evaporation. The residue
was taken up in EtOAc (500 mL), washed with salt solution (100 mL),
dried over Na2SO4, filtered, and concentrated to the crude solid product.
The pure product was isolated by column chromatography on silica,
eluting with CHCl3 (100%). After solvent removal, the product was
isolated as a white solid (5.3 g, 40%): 1H NMR (CDCl3) δ 7.64 (d,
2H, J ) 7.8) 7.29 (d, 2H, J ) 7.8), 3.50 (m, 1H), 2.98 (t, 2H, J ) 7.8),
2.43 (s, 3H), 1.70-1.40 (m, 4H), 0.83 (t, 1H, J ) 6.6); 13C NMR
(CDCl3) δ 143.42, 138.26, 129.88, 126.85, 54.90, 46.89, 35.65, 24.24,
21.39, 11.06; MS (CI/NH3) 735 (M+ + 1). Anal. Calcd for
C36H51N3O6S3: C, 60.02; H, 7.17; N, 5.85. Found: C, 59.97; H, 7.28;
N, 5.85.
N,N′,N′′-Tripropyl-1,3,5-cis,cis-triaminocyclohexane Trihydro-
bromide (tach-Pr3‚3HBr). A flask was charged with acetic anhydride
(ACS reagent grade, 98%) (16.55 mL) and cooled in an ice bath.
Concentrated HBr (40.83 mL) was added slowly, and the solution was
allowed to stir at room temperature for 18 h. tachTs3Pr3 (5.0 g, 7.0
mmol) was added, and the suspension was refluxed for 24 h during
which a dark red-brown solution formed. The solution was rotary
evaporated to leave a dark solid which was taken up in H2O (25 mL)
and extracted with Et2O (2 × 50 mL). The aqueous layer was filtered
and concentrated to ca. 10 mL. This residue was taken up in 100%
EtOH (ca. 50 mL), and an equal amount of Et2O was added to
precipitate the product. The white suspension was cooled at 4 °C for
18 h, and then the solid was collected, washed with Et2O, and dried
under vacuum (3.2 g, 92%): 1H NMR (D2O) δ 3.47 (tt, 1H, J ) 11.7,
3.5), 3.11 (t, 2H, J ) 7.8), 2.64 (br d, 1H, J ) 10.8), 1.80-1.59 (m,
3H), 1.00 (t, 3H, J ) 7.8); 13C NMR (D2O) δ 54.82, 49.85, 32.97,
22.28, 13.11; MS (CI/NH3) 256 (M+ + 1). Anal. Calcd for C15H33N3-
(HBr)3: C, 36.14; H, 6.69; N, 8.43. Found: C, 36.27; H, 6.71; N, 8.34.
1,3,5-cis,cis-Triaminocyclohexane-N,N′,N′′-tris(neopentyl-
imine). Tach‚3HBr (2.0 g, 5.4 mmol) was dissolved in H2O (10 mL)
with NaOH (0.695 g, 16.1 mmol) to form a clear solution. Benzene
(150 mL) was added, and the water was removed by azeotropic
distillation with a Dean-Stark trap. Pivaldehyde (1.39 g, 16.1 mmol)
was added during this process, which was then continued for 12 h.
After cooling, the solution was decanted and rotary evaporated to a
white solid (1.57 g, 87%): 1H NMR (CDCl3) δ 7.56 (s, 1H), 3.18 (m,
1H), 1.70 (q, 1H, J ) 11.7), 1.63 (m, 1H), 1.04 (s, 9H); 13C NMR
(CDCl3) δ 170.14, 65.71, 40.81, 35.71, 26.85; MS (CI/NH3) 334 (M+
+ 1). Anal. Calcd for C21H39N3: C, 75.60; H, 11.80; N, 12.60. Found:
C, 75.79, H, 11.73; N, 12.32.
1,3,5-cis,cis-Triaminocyclohexane-N,N′,N′′-tris(methylenefu-
ran) (tach-furan3). The above imine (3.00 g, 8.26 mmol) was dissolved
in MeOH (100 mL) and treated with NaBH4 (1.23 g, 32.25 mmol) as
described for tach-neopentyl3. Workup afforded the product as an oil
(2.68 g, 88%): 1H NMR (CDCl3) δ 7.36 (s, 1H), 6.31 (m, 1H), 6.16
(d, 2H, J ) 3.3), 3.80 (s, 2H), 2.54 (tt, 1H, J ) 10.8, 3), 2.15 (d, 1H,
J ) 11.7), 1.70 (br s, 1H), 0.96 (q, 1H, J ) 11.7); 13C NMR (CDCl3)
δ 153.92, 141.867, 110.15, 106.81, 52.66, 43.22, 39.66; MS (CI/NH3)
370 (M+ + 1). Anal. Calcd for C21H27N3O3; C, 68.26; H, 7.38; N,
11.37. Found: C, 68.26; H, 7.52; N, 11.43.
Metal Complex Syntheses. [Cu(tach-Me3)Cl2]. A mixture of tach-
Me3‚3HBr (0.12 g, 0.29 mmol) in water (5 mL), Na2CO3‚H2O (0.054
g, 0.44 mmol, 1.5 equiv) in water (5 mL), and benzene (100 mL) was
stirred and heated in a 250 mL round-bottomed flask fitted with a
Dean-Stark trap with a water-cooled condenser. Benzene-water
azeotrope was distilled for 14 h with collection of ca. 11.7 mL of water.
The benzene layer was transferred to another 250 mL round-bottomed
flask and dried under reduced pressure to give tach-Me3 as a white
solid. The solid was dissolved in a mixture of CHCl3 (2 mL) and Et2O
(4 mL) and added to a green solution of CuCl2 (0.040 g, 0.29 mmol)
in a mixture of MeOH/Et2O (2 mL/4 mL) affording a green precipitate
immediately. Decanting the supernatant and extracting the solid with
CH2Cl2 (5 mL) followed by drying under reduced pressure afforded
the product as a green solid (0.056 g, 0.18 mmol, 63%). Anal. Calcd
for C9H21N3CuCl2 (Cu(tach-Me3)Cl2): C, 35.36; H, 6.92; N, 13.74.
Found: C, 35.16; H, 6.85; N, 13.62. UV (MeOH): 687 nm (ꢀ ) 111.7).
MS (FAB/DMSO/glycerol): 234 (M - 2Cl-).
[Cu(tach-Et3)Br0.8Cl1.2]. An aqueous solution (3 mL) of tach-Et3‚
3HBr (0.193 g, 0.426 mmol) was neutralized by adding 12.8 mL of
0.100 N NaOH solution (0.103 mmol, 3 equiv). The neutralized ligand
was dried under reduced pressure for 10 h and extracted into CHCl3
(12 mL). This solution was filtered and dried under reduced pressure.
The resulting pale-yellow solid was taken up in CHCl3 (3 mL) and
added to a pale green solution of CuCl2 (0.0573 g, 0.426 mmol) in
anhydrous MeOH (2 mL) affording a dark green solution. The dark
green solution was filtered and dried under reduced pressure. The dried
crude product was dissolved in anhydrous MeOH (5 mL), and
anhydrous Et2O was diffused into MeOH solution yielding green
microcrystals (0.0541 g, 0.156 mmol, 35.5%). The average proportions
of Br and Cl are indicated by the elemental analysis; however, X-ray
crystallographic analysis of a particular crystal of this material indicated
the composition [Cu(tach-Et3)Br0.8Cl1.2] (see below). Anal. Calcd for
C12H27Br0.7Cl1.3CuN3 (Cu(tach-Et3)Br0.7Cl1.3 (specific proportion Br:Cl
varies): C, 38.04; H, 7.18; N, 11.09. Found: C, 38.47; H, 6.71; N,
10.45. UV (MeOH): 716 nm (ꢀ ) 132.8). MS (FAB/glycerol): 276
(M - 2X-).
N,N′,N′′-Trineopentyl-1,3,5-cis,cis-triaminocyclohexane (tach-
neopentyl3). The above imine (2.00 g, 6.01 mmol) was dissolved in
MeOH (100 mL), and NaBH4 (1.37 g, 3.67 mmol) was added. The
reaction mixture was stirred for 12 h after which the solvent was
removed by rotary evaporation. The residue was taken up in CHCl3
(100 mL) and stirred vigorously with a 1:1 mixture of saturated salt
solution and 5% NaHCO3 (100 mL). The layers were separated, and
the CHCl3 solution was washed with saturated salt solution (2 × 100
mL), dried over Na2SO4, filtered, and rotary evaporated to leave the
product (1.89 g, 93%): 1H NMR (CD3OD) δ 4.88 (s, 1H), 2.51 (tt,
1H, J ) 11.7, 3.9), 2.43 (s, 2H), 2.18 (br d, 1H, J ) 12.0), 1.03 (q,
1H, J ) 11.7), 0.94 (s, 9H); 13C NMR (CD3OD) δ 60.38, 56.62, 39.31,
32.15, 28.32; MS (CI/NH3) 340 (M+ + 1). Anal. Calcd for C21H45N3:
C, 74.25; H, 13.38; N, 12.37. Found: C, 74.28, H, 13.20; N, 12.28.
1,3,5-cis,cis-Triaminocyclohexane-N,N′,N′′-tris(2-methylfuran-
imine). tach‚3HBr (4.0 g, 10.8 mmol) was dissolved in H2O (10 mL)
[Cu(tach-Et3)Cl2]. A mixture of tach-Et3‚3HBr (0.17 g, 0.37 mmol)
in water (5 mL), Na2CO3‚H2O (0.073 g, 0.59 mmol, 1.6 equiv) in water
(5 mL), and benzene (100 mL) was stirred and heated in a 250 mL
round-bottomed flask fitted with a Dean-Stark trap with a water-cooled
condenser. Benzene-water azeotrope was distilled for 14 h with
collection of ca. 11.9 mL of water. The benzene layer was dried under
reduced pressure to give tach-Et3 as a white solid. A pale yellow solution
of tach-Et3 (0.079 g, 0.37 mmol) in a mixture of MeOH (2 mL) and
Et2O (4 mL) was added to a pale green solution of CuCl2 (0.050 g,
0.37 mmol) in a mixture of MeOH (3 mL) and Et2O (6 mL) producing
a dark green solution and a brown precipitate. The brown precipitate
was filtered away, and the dark green filtrate was dried under reduced

4170 Inorganic Chemistry, Vol. 40, No. 17, 2001
Park et al.
pressure affording a green solid. The green solid was dissolved in CH2-
Cl2 (4 mL), and Et2O was diffused into the solution affording green
prisms (0.053 g, 0.15 mmol, 43%). Anal. Calcd for C12H27N3CuCl2
(Cu(tach-Et3)Cl2): C, 41.44; H, 7.82; N, 12.08. Found: C, 41.22; H,
7.83; N, 11.94. UV (MeOH): 718 nm (ꢀ ) 97.0). MS (FAB/glycerol):
276 (M - 2Cl-).
Table 1. Crystal Data and Structure Refinement for
[Cu(tach-Et3)Br0.8Cl1.2
]
empirical formula
fw
C12H27Br0.8Cl1.2CuN3
383.37
temp
cryst system
space group
173(2) K
orthorhombic
Pnma
[Cu(tach-Pr3)Cl2]. A mixture of tach-Pr3‚3HBr (0.250 g, 0.505
mmol) in water (5 mL), Na2CO3‚H2O (0.100 g, 0.808 mmol, 1.6 equiv)
in water (5 mL), and benzene (100 mL) was stirred and heated in a
250 mL round-bottomed flask fitted with Dean-Stark trap with a water-
cooled condenser. Benzene-water azeotrope was distilled for 14 h with
collection of ca. 11.7 mL of water. The benzene layer was dried under
reduced pressure to give tach-Pr3 as a white solid. To a pale green
solution of CuCl2 (0.0678 g, 0.505 mmol) in a mixture of MeOH (2
mL) and Et2O (6 mL) was added a pale yellow solution of neutralized
tach-Pr3 (0.127 g, 0.505 mmol) in a mixture of MeOH (2 mL) and
Et2O (6 mL) affording a dark green solution. Turquoise, featherlike
crystals formed upon standing and were isolated by decanting the
supernatant. The crystals were dried under reduced pressure, extracted
into CH2Cl2 (5 mL) and filtered, and dried again under reduced pressure
to afford the turquoise product (0.140 g, 0.363 mmol, 72%). Anal. Calcd
for C15H33N3CuCl2 (Cu(tach-Pr3)Cl2): C, 46.21; H, 8.53; N, 10.78.
Found: C, 46.33; H, 8.36; N, 10.63. UV (MeOH): 703 nm (ꢀ ) 95.9).
MS (FAB/glycerol/DMSO/EtOH): 318 (M - 2Cl-).
a
b
c
V
8.2265(1) Å
12.5313(1) Å
15.3587(3) Å
1583.31(4) Å3
4
Z
d(calcd)
abs coeff
F(000)
cryst size
1.608 Mg/m3
3.589 mm-1
790
0.10 × 0.16 × 0.32 mm
2.10-27.86°
9500
1952 (Rint ) 0.0411)
1551 ([I > 2σ(I)])
SADABS
θ
range for data collcn
reflcns collcd
indepdt reflcns
obsd reflcns
abs corr
range of relat transm factors
data/restraints/params
goodness-of-fit on F2
SHELX-93 weight params
final R indices [I > 2σ(I)]
R indices (all data)
0.97 and 0. 68
1948/0/100
1.070
0.0461, 1.3522
R1 ) 0.0413, wR2 ) 0.0900
R1 ) 0.0596, wR2 ) 0.1000
0.0017(5)
[Cu(tach-furan3)Cl2]. A yellowish solution of tach-furan3 (0.0549
g, 0.149 mmol) in MeOH (2 mL) was added to a green solution of
CuCl2 (0.0209 g, 0.154 mmol) in MeOH (2 mL) affording a deep green
solution. Diethyl ether was diffused into the mixture solution for 5
days yielding green crystals and a yellow-green powder. Decanting the
supernatant and extraction with CH2Cl2 (5 mL) followed by Et2O
diffusion into the CH2Cl2 solution afforded green prisms. The prisms
were isolated by filtration and dried under reduced pressure. Yield:
0.0321 g (0.0637 mmol, 42.8%). Anal. Calcd for C21H27N3Cl2CuO3
(Cu(tach-furan3)Cl2): C, 50.05; H, 5.40; N, 8.34. Found: C, 49.84; H
5.39; N, 8.22. UV (MeOH): 700 nm (ꢀ ) 100.9). MS (FAB/DMSO/
glycerol): 432 (M - 2Cl-).
extinction coeff
largest diff peak and hole
0.614 and -0.594 e Å-3
(2:1) (3 mL), pH 7.4, at 25 °C, affording a suspension which clarified
to turquoise 5 mM [Cu(tach-Pr3)]2+ upon addition of MeOH (3 mL).
[Cu(tach-thioph3)]2+. The green solid [Cu(tach-thioph3)Cl2]18 (0.017
g, 30 µmol) was dissolved in a mixture 50 mM HEPES/glycerol (2:1)
(3 mL), pH 7.4, at 25 °C, affording a green cloudy solution which
became a clear green 5 mM [Cu(tach-thioph3)]2+ solution by adding
EtOH (3 mL).
In Situ Preparations of [Cu(tach-R3)]2+ in Aqueous or Aqueous/
Alcoholic Media.
X-ray Data Collection, Structure Solution, and Refinement for
[Cu(tach-Et3)Br0.8Cl1.2]. Crystals of Cu(tach-Et3)Br0.8Cl1.2 suitable for
study were obtained by vapor phase diffusion of Et2O into a CH2Cl2
solution of product. A fragment was taken directly from the crystals in
supernatant, sealed in epoxy, and mounted on a glass fiber. Data were
collected on a Siemens SMART/CCD area detector diffractometer (-10
e h e 10, -16 e k e 13, -14 e l e 20; 2.10 e θ e 27.86°) at -100
°C with graphite-monochromated Mo KR radiation (0.710 73 Å). A
total of 9500 reflections were measured; 1952 reflections were unique
(Rint ) 0.0411), and 1551 reflections with I > 2σ(I) were considered
to be observed for purposes of R value computation. The data were
corrected for Lorentz and polarization factors. A summary of data
collection parameters is given in Table 1.
[Cu(tach-Me3)]2+. A colorless solution of 0.100 M tach-Me3‚3HBr
in water (1.50 mL) (prepared by neutralization of tach-Me3‚3HBr
(0.0621 g, 0.150 mmol) in water (1.036 mL) with 3 equiv of 1.02 N
NaOH (0.464 mL)) was added to a blue solution of 0.100 M CuCl2 in
water (1.49 mL), affording a deep blue 50 mM [Cu(tach-Me3)]2+
solution. Occasionally, a faint blue-green precipitate formed, presumably
insoluble Cu(II) hydroxide, which was removed by filtration. From this
stock solution was prepared a 5 mM [Cu(tach-Me3)]2+ solution by
further dilution with a mixture of 50 mM HEPES/glycerol (2:1), pH
7.4, at 25 °C.
63CuCl2/DCl. A ca. 10 mg amount of 63Cu metal was dissolved in
6 N HNO3 and the resulting solution evaporated to dryness under a
stream of dry nitrogen gas. The solid copper nitrate was dissolved in
sufficient 0.01 N DCl to provide a 20 mM solution of 63Cu(II).
Tach-Me3‚3DCl. A clear solution of tach-Me3‚3HBr (0.033 g, 80
µmol) in D2O was treated with DCl (1 mL of 37% w/w in D2O), and
dried under reduced pressure affording a white solid. The procedure
was repeated two more times giving the product tach-Me3‚3DCl as a
white solid. FT-IR: 2100 cm-1 (N-D).
The structure was solved by direct methods. It was immediately
obvious from refinement of the unique halide position that a minor Br
impurity was present. The disorder was not resolvable, and the
crystallographic position was refined with partial Cl and Br occupancy.
The occupancy factors were refined to values of 0.8 for Br and 1.2 for
Cl. In addition to the disorder mentioned above, one N-Et group was
fractionally disordered across a mirror plane. Both N1 and C5 (Figure
1) were refined at 50% occupancy just off the mirror site. The terminal
methyl group (C6) resided on the mirror and was not disordered.
Although lowering the symmetry to Pnm21 would remove the mirror
plane, only N1 and C5 would be affected. Thus, when this was
attempted, the remaining mirror related atoms showed high correlations
and would not refine properly. Electron density consistent with the N1,
C5 disorder was also still present. The symmetry was returned to Pnma
and the refinement completed in this space group. The geometrically
constrained hydrogen atoms were placed in calculated positions and
allowed to ride on the bonded atom with B ) 1.2Ueqv(C). The methyl
hydrogen atoms were included as a rigid group with rotational freedom
at the bonded carbon atom (B ) 1.2Ueqv(C)). The remaining three
hydrogen atoms were located from a difference Fourier map and
[63Cu(tach-Me3)]2+. A pale blue solution of 20 mM 63CuCl2/DCl
(0.25 mL, 5.0 µmol) was added to a clear solution of tach-Me3‚3DCl
(0.014 g, 5.0 µmol) in a mixture of 50 mM HEPES/glycerol-d3 (2:1),
pH 7.4, at 25 °C (0.75 mL), affording 5 mM [63Cu(tach-Me3)]2+
.
[Cu(tach-Et3)]2+. To a blue solution of CuCl2 (0.0201 g, 0.150
mmol) in water (1.5 mL) was added a clear solution of tach-Et3‚3HBr,
neutralized by 3 equiv of 1.0 N NaOH (0.0681 g, 0.150 mmol) in water
(1.5 mL) to form a blue [Cu(tach-Et3)]2+ solution with a small amount
of faint blue-green precipitate, presumably insoluble Cu(II) hydroxides,
which was removed by filtration. From this stock solution was prepared
a 5 mM [Cu(tach-Et3)]2+ solution by further dilution with a mixture of
50 mM HEPES/glycerol (2:1), pH 7.4, at 25 °C.
[Cu(tach-Pr3)]2+. The turquoise solid [Cu(tach-Pr3)Cl2] (0.012 g,
0.30 mmol) was dissolved in a mixture of 50 mM HEPES/glycerol

Copper(II) Complexes of N-Alkylated Derivatives
Inorganic Chemistry, Vol. 40, No. 17, 2001 4171
Table 2. Selected Bond Lengths (Å) and Angles (deg) of
[Cu(tach-Et3)Br0.8Cl1.2
]
Cu-N(2)
2.053(2)
2.3948(6)
1.524(6)
1.498(4)
1.517(5)
1.528(7)
Cu-N(1)
2.218(5)
1.478(7)
1.484(4)
1.519(5)
1.515(4)
1.506(5)
Cu-ClBr
N(l)-C(1)
N(2)-C(3)
C(2)-C(3)
C(5)-C(6)
N(1)-C(5)
N(2)-C(7)
C(1)-C(2)
C(3)-C(4)
C(7)-C(8)
N(2)-Cu-N(2A)a
N(2)-Cu-N(l)
N(2A)a-Cu-ClBr
N(1)-Cu-ClBr
C(5)-N(l)-C(l)
C(1)-N(1)-Cu
C(7)-N(2)-Cu
91.98(14) N(2)-Cu-N(1A)a
83.94(14) N(2)-Cu-ClBr
167.63(8) N(1A)a-Cu-ClBr
96.75(14)
86.24(7)
108.42(12)
95.24(12) ClBr-Cu-ClBr(A)a 92.89(3)
109.6(4)
109.5(3)
111.7(2)
C(5)-N(1)-Cu
C(7)-N(2)-C(3)
C(3)-N(2)-Cu
C(2)-C(l)-N(1)
C(3)-C(2)-C(1)
N(2)-C(3)-C(2)
111.0(3)
114.2(2)
115.7(2)
99.7(3)
114.6(3)
110.7(3)
C(2)-C(l)-C(2A) a 110.2(4)
Figure 1. ORTEP view of [Cu(tach-Et3)Br0.8Cl1.2] showing mirror
disorder (50% probability ellipsoids). The A-suffixed atoms are
generated by crystallographic mirror symmetry. Atoms N1A and C5A
are also disordered with N1 and C5 about the plane. Hydrogens have
been omitted for clarity.
C(2)-C(l)-N(1A) a 122.6(3)
N(2)-C(3)-C(4)
C(4)-C(3)-C(2)
N(1)-C(5)-C(6)
112.0(3)
110.9(3)
113.0(4)
C(3A)a-C(4)-C(3) 112.9(4)
N(2)-C(7)-C(8)
114.7(3)
a Equivalent atoms with the suffix “A” are generated by the symmetry
transformation x, -y + 1/2, z.
allowed to ride on the bonded N atoms with B ) 1.2Ueqv(N). Refinement
of the non-hydrogen atoms was carried out with anisotropic temperature
factors. Final values of R(all data) ) 0.0596, Rw(all data) ) 0.1000,
R(obs data) ) 0.0413, and Rw(obs data) ) 0.0900 were obtained with
a GOF (on F2) of 1.070 and SHELX-93 weight parameters of 0.0461
and 1.3522.
Structural Study of [Cu(tach-Et3)Br0.8Cl1.2]. The [Cu(tach-
Et3)Br0.8Cl1.2] molecule resides on a crystallographic mirror
plane that generates the atoms N2A, ClBrA, C3A, C2A, C7A,
and C8A (Figure 1). Fractional disorder of one N-CH2 group
about the mirror plane generates the atom pairs (N1, N1A) and
(C5, C5A). Selected bond distances and angles are in Table 2.
The metal coordination sphere is nearly square pyramidal, with
the N1/N1A position in the apical coordination site and N2,
N2A and the halides forming the square base (Figure 1). The
apical atom (N1/N1A) deviates slightly from square pyramidal
geometry, which may be an artifact of the disorder. However,
a distorted square pyramidal coordination sphere is supported
by EPR and optical data (see below). The deviation is such that
the Cu-N1 or Cu-N1A bond axis is not normal to the N2X2
plane. This structure contrasts with that of [Cu(tach-thioph3)-
Cl2] whose Cu coordination sphere distorts toward trigonal
bipyramidal geometry.18 The apical bond distance Cu-N(1) of
2.218(5) Å is longer than the basal one (2.053(2) Å), as is typical
of Jahn-Teller-distorted Cu(II). This Cu-Napical bond length
is slightly shorter than that of [Cu(tach-thioph3)Cl2] (2.288(3)
Å), which might be ascribed to a steric effect or again to disorder
effects. The Cu-Napical bond also appears marginally shorter
than those of Cu([9]aneN3)Cl225 and Cu([9]aneN3)Br2,26 which
are 2.246(4) and 2.231(4) Å, respectively. The Cu-Nbasal
distance of the title compound (2.053(2) Å) is comparable to
all distances of Cu[(tach-thioph3)Cl2], Cu([9]aneN3)Cl2,25 and
Results
Ligand Syntheses. The tach-Pr3 derivative was prepared as
the trihydrobromide salt by modification of the syntheses of
previously reported tach,19 tach-Me3, and tach-Et3.20 The steri-
cally bulky neopentyl and the 2-furanylmethyl derivatives were
synthesized analogously to the 2-thienylmethyl derivative, tach-
thioph3,18 by formation of the triimine followed by reduction
with excess borohydride. This route obviated concerns about
acid-promoted rearrangements of the neopentyl group as well
as steric challenges to alkylation that could arise in the method
employed for tach-Me3 and tach-Et3.20
Cu(II) Complex Syntheses. The complexes [Cu(tach-R3)-
Cl2] were prepared from the appropriate copper salts and free
triamines in analogy to the previously reported [Cu(tach-
thioph3)Cl2].18 In one case, tach-Me3‚3HBr was not fully
converted to the free triamine and the remaining trace of bromide
ions resulted in the mixed anion product [Cu(tach-Et3)Br0.8Cl1.2],
which was structurally characterized. Subsequently, [Cu(tach-
Et3)Cl2] was prepared and used for further studies; it was
demonstrated that all relevant properties of the two substances
were identical.
26
Cu([9]aneN3)Br2 (range 2.038(4)-2.069(3) Å).
Attempts to prepare [Cu(tach-neopentyl3)Cl2] thus far have
yielded impure materials of poor solubility. The steric effect of
neopentyl groups may serve to energetically bias this ligand
toward the N3-triequatorial conformation, preventing formation
of a discrete complex and instead favoring a polymeric structure
with each copper bound to multiple, bridging tach ligands.
In situ preparation of aqueous [Cu(tach-R3)]2+ (R ) Me, Et)
was accomplished by adding a slight excess (<1%) of tach-
R3(aq) to CuCl2(aq) at pH 7. At concentrations above ca. 1 mM,
precipitation of uncharacterized blue solids occurred outside the
pH range 6.71 to 11.22 or in the absence of a slight excess of
ligand. The Cu(II) complexes of other tach-R3 (R ) n-Pr, CH2-
2-thienyl, and CH2-2-furanyl) were solubilized by MeOH as
cosolvent. Attempts to obtain an accurate base titration of a
mixture of tach-R3‚3HBr and Cu2+(aq) in order to determine
pKa’s and stability constants were not successful, due to the
limitations of pH range and solubility in this system.
The torsion angles C-C-C-C of the cyclohexyl ring, a
measure of ligand distortion induced by the metal pushing the
nitrogens outward27,28 are the following: C(2A)-C(1)-C(2)-
C(3), 50.6(5)°; C(1)-C(2)-C(3)-C(4), 52.6(4)°; C(2)-C(3)-
C(4)-C(3A), 53.4(4)°. These are not significantly different from
those of Cu[(tach-thioph3)Cl2], which range from 48.23(41) to
55.29(39)°.18 There are no significant intermolecular contacts
in the structure.
(24) Brand, U.; Vahrenkamp, H. Inorg. Chim. Acta 1992, 198-200, 663.
(25) Schwindinger, W. F.; Fawcett, T. G.; Lalancette, R. A.; Potenza, J.
A.; Schugar, H. J. Inorg. Chem. 1980, 19, 1379.
(26) Bereman, R. D.; Churchill, M. R.; Schaber, P. M.; Winkler, M. E.
Inorg. Chem. 1979, 18, 3122.
(27) Hilfiker, K. A.; Rogers, R. D.; Brechbiel, M. W.; Planalp, R. P. Inorg.
Chem. 1997, 36, 4600.
(28) Choquette, D. M.; Buschmann, W. E.; Olmstead, M. M.; Planalp, R.
P. Inorg. Chem. 1993, 32, 1062.

4172 Inorganic Chemistry, Vol. 40, No. 17, 2001
Park et al.
EPR Spectroscopy. Figures 3-6 illustrate the EPR spectra
of the various complexes at X-band (9.15 GHz) and Q-band
(35 GHz) microwave frequencies. The Q-band spectrum (Figure
3) of the powdered sample of [Cu(tach-Et3)Cl2] shows near axial
magnetic symmetry with a small in-plane anisotropy, namely
gx ) 2.061, gy ) 2.071, and gz ) 2.262, consistent with the
distorted square pyramidal structure of the complex (Figure 1).
The X-band solution frozen aqueous solution spectra at 77 K
of all the complexes prepared with natural abundance 63,65Cu
(I ) 3/2) are very similar (Figure 4) as are their visible-near-
infrared spectra (Table 3), indicating essentially identical first
coordination spheres for all of them. The same spectra are
observed whether pure solid is dissolved in buffer or the
complex is prepared in situ from CuCl2 and ligand. The 63Cu
EPR spectra at X-band are characteristic of monomeric copper
species in solution. Because the low-field parallel lines are rather
broad, ∆B1/2 ∼ 7 mT, they show no evidence of ligand 14N (I
) 1) superhyperfine couplings (Figure 4), even for samples
prepared with isotopically pure 63Cu or with D2O solvent in
which the parallel lines are slightly sharpened. Basal 14N
superfine splittings are typically only 1.0-1.5 mT for square
pyramidal Cu(II) complexes, and apical nitrogen couplings are
much less, ∼0.25 mT,34-36 and would not be resolved in the
spectrum.
Q-band spectra (Figure 5) were measured to resolve the
intense perpendicular region of the X-band spectra (Figure 4)
into the principal g-factor components. The four (mI ) (3/2,
(1/2) copper hyperfine parallel lines are fully separated from
the perpendicular line at the higher frequency, but there is no
evidence of in-plane x,y-anisotropy in g or in the 63Cu hyperfine
coupling within the width of the intense perpendicular EPR line
(Figure 5). An in-plane g-anisotropy of gy - gx ) 0.010
comparable to that seen for the solid [Cu(tach-Et3)Cl2] sample
(Figure 3) would not be resolved within the peak-to-peak width,
∆Bpp ) 10.5 mT, of the perpendicular line of the Q-band
spectrum of the complexes (Figure 5).
The frozen solution spectra were analyzed according to the
simplified spin Hamiltonian, H ) g|âBzSz + g â(BxSx + BySy)
+ A|SzIz + A (SxIx + SyIy). Here all of the symbols have their
usual meanings. A , which is not resolved in the frozen solution
spectra, was back-calculated from the value of Ao determined
from the room-temperature spectra in Figure 6, i.e., Ao ) A|/3
+ 2A /3, assuming the same sign for all of the couplings. The
spin Hamiltonian parameters for all of the complexes are
summarized in Table 4. Second-order corrections were applied
to the X-band spectra but were not required at Q-band. Spin
Hamiltonian parameters for the [Cu(tach-Et3)Cl2] complex in
methanol are not reported since only a broad relatively feature-
less EPR spectrum (not shown) was obtained in frozen solution
at X-band and Q-band, suggestive of solute aggregation upon
freezing the sample.
The room-temperature EPR spectra depicted in Figure 6 show
increased line broadening with molecular weight that we
attribute to the longer rotational correlation times of the larger
complexes.37 The close correspondence between go obtained
directly from the room-temperature spectrum and that calculated
from the frozen aqueous solution spectrum via the equation go
) g|/3 + 2g /3 (Table 4) suggests that the structures of the
Figure 2. Visible/near-infrared spectra of [Cu(tach-Et3)Cl2]. The
solution-phase spectrum (MeOH, 5 mM) has been simulated (see text).
The experimental curve (solid line) is offset by +0.01 absorbance units
in order to show the match with the simulated curve (dotted line). The
inset depicts the solid-phase spectrum.
Electronic Spectroscopy. Figure 2 shows the visible/near-
infrared spectrum of the [Cu(tach-Et3)Cl2] complex in MeOH;
very similar spectra were obtained for all of the complexes in
methanol and aqueous buffer except that the bands were shifted
to higher energy in water. The spectra could be satisfactorily
fitted to a sum of three Gaussian functions ꢀ(ν) of the form
ꢀ(ν) ) ꢀmax exp[-(ln 2)4(νmax - ν)2/∆ν1/22], where ꢀmax and
νmax are the molar absorptivity and frequency (cm-1) of the
maximum absorption and ∆ν1/2 is the full width at half-height
of the absorption band. Oscillator strengths, f, were calculated
from the relationship f ) 4.33 × 10-9∫ꢀ(ν) dν.29 Spectral data
for the complexes in HEPES buffer and in MeOH are sum-
marized in Table 3 as well as data for solid [Cu(tach-Et3)Cl2].
2
2
We assign the three Gaussian bands to the metal-based dx -y
2
f dz , dxy, dxz,yz transitions (electron hole formalism) in order
of increasing energy as per the work of Duggan et al. on square
pyramidal copper complexes.30 The molar absorptivities ∼ 10-
80 M-1 cm-1 and oscillator strengths ∼ 0.2 × 10-6-6.5 ×
10-6 (Table 3) are typical of d-d bands of square pyramidal
copper30,31 and of transition ion complexes where parity-
forbidden Laporte selection rules are relaxed by lowered
symmetry.29 The dx -y f dz transition at ∼8500 cm-1 is near
the low end of ligand field transition energies seen for Cu(II)
complexes and reflects the relatively strong axial component
of the ligand field produced by the apical nitrogen (N1/N1A in
Figure 1) of the complex.32,33 The band positions of all the
complexes in methanol and of the solid-state sample of [Cu-
(tach-Et3)Cl2] (Figure 2) are similar (Table 3), suggesting that
the complexes in methanol and the solid state have essentially
the same structure. However, in aqueous media, the bands are
approximately 1000 cm-1 higher in energy, indicating that a
structural change has occurred. We attribute the blue shift to
the replacement of Cl- by the stronger field ligand H2O in the
first coordination sphere. This interpretation is further supported
by EPR data and bonding parameters derived below and is
consistent with the preference of Cu(II) for H2O over Cl- as a
ligand. We therefore write the formula for this complex in
2
2
2
aqueous solution as [Cu(tach-Et3)(H2O)2]2+
.
(29) Figgis, B. N. Introduction to Ligand Fields; Wiley: New York, 1966;
p 208.
(30) Duggan, M.; Ray, N.; Hathaway, B.; Tomlinson, A. A. G.; Brint, P.;
Pelin, K. J. Chem. Soc., Dalton Trans. 1980, 1342.
(31) Karlin, K. D.; Hayes, J. C.; Juen, S.; Hutchinson, J. P.; Zubieta, J.
Inorg. Chem. 1982, 21, 4106.
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R. T. A.; Grady, J. K.; Chasteen, N. D. Biochemistry 1997, 36, 14853.
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Copper(II) Complexes of N-Alkylated Derivatives
Inorganic Chemistry, Vol. 40, No. 17, 2001 4173
a
Table 3. Assignments for the Optical Spectra of Cu(II) Complexes of tach-R3
b
b
b
2
complexes
∆Exz,yz
∆Exy
∆Ez
[Cu(tach-Me3)Cl2] in MeOH
[Cu(tach-Et3)(H2O)2]2+ in HEPES
[Cu(tach-Et3)Cl2] in MeOH
[Cu(tach-Et3)Cl2] powder
[Cu(tach-Pr3)Cl2] in MeOH
[Cu(tach-furan3)Cl2] in MeOH
[Cu(tach-thioph3)Cl2] in MeOH
14 252 (76.2, 6.07)
14 972 (54.4,5.94)
14 252 (76.2, 6.07)
14 496
14 482 (75.0, 6.42)
14 472 (56.2, 4.48)
14 892 (43.0, 3.96)
12 316 (24.4, 1.79)
12 594 (17.8, 0.25)
12 321 (23.8, 1.75)
12 544
12 491 (19.4, 1.52)
12 481 (11.8, 0.92)
12 656 (4.4, 0.43)
8388 (31.8, 2.57)
9580 (22.0,1.88)
8398 (31.8, 2.57)
8223
8588 (31.8, 2.58)
8698 (26.2, 0.21)
9128 (19.2, 1.61)
a Band maxima in cm-1 from Gaussian fitting of the absorption spectra. Errors nominally (10 cm-1. Molar absorptivities (M-1 cm-1) and
b
oscillator strengths (10-6), respectively, in parentheses. Exz,yz ) Ex -y - Exz,yz; ∆Exy ) Ex -y - Exy; ∆Ez ) Ex -y - Ez .
2
2
2
2
2
2
2
2
Figure 3. Q-band EPR spectrum of powdered [Cu(tach-Et3)Cl2] at
room temperature.
Figure 5. Q-band EPR spectra of [Cu(tach-R3)]2+(aq) in frozen (100
K) HEPES/glycerol buffer, pH 7.4.
Figure 4. X-band EPR spectra of [Cu(tach-R3)]2+(aq) in frozen (77
K) HEPES/glycerol buffer, pH 7.4.
Figure 6. X-band EPR spectra of [Cu(tach-R3)]2+(aq) in room-
temperature HEPES buffer, pH 7.4. A-E correspond to Cu(II)
complexes of ligands tach-R3, R ) Me, Et, n-Pr, thioph, and furan,
respectively. DPPH is the g-mark standard (g ) 2.0037) diphenylpi-
crylhydrazyl radical.
complexes in water are essentially the same in the liquid and
frozen states. In general, the spin Hamiltonian parameters are
very similar for all of the tach complexes in aqueous media
(Table 4), including that of tach-thioph3, whose Cu(II) structure
has been previously determined.18 We conclude that steric effects
from substituents on the coordinating nitrogens do not signifi-
cantly alter the first coordination sphere structure of any of the
complexes. Moreover, the similarity in the spin Hamiltonian
parameters of the N-ethyl compound in pH 7.4 and pH 10.1
solutions (Table 4) indicates that the complex does not undergo
appreciable hydrolysis at the higher pH. In general, all of the
spectra are consistent with the presence of one major species

4174 Inorganic Chemistry, Vol. 40, No. 17, 2001
Table 4. Spin Hamiltonian Parametersa
Park et al.
c
copper complexes
g0
g//
2.264
2.265
2.266
g
A0 (10-4 cm-1
)
A| (10-4 cm-1
)
A (10-4 cm-1
)
[Cu(tach-Me3)(H2O)2]2+ d
[63Cu(tach-Me3)(H2O)2]2+ d
[Cu(tach-Et3)(H2O)2]2+ d
[Cu(tach-Et3)(H2O)2]2+ f
[Cu(tach-Et3)Cl2] powderb
2.127
2.132e
2.128
2.128e
2.131g
2.066
2.066
2.066
58.0
166.9
164.2
164.3
165.0
3.5
55.5
1.2
2.263
gz ) 2.262
2.061
gx ) 2.061
gy ) 2.071
2.065
[Cu(tach-Pr3)(H2O)2]2+ d
[Cu(tach-furan3)(H2O)2]2+ d
[Cu(tach-thioph3)(H2O)2]2+ b
2.127
2.127
2.124
2.266
2.261
2.261
59.3
58.8
60.5
164.6
164.0
165.7
6.7
6.2
8.0
2.064
2.063
a g values have errors of (0.001, and hyperfine couplings have errors of (0.2 × 10-4 cm-1. Anisotropic parameters were measured from Q-band
spectra of frozen solutions at Q-band frequency at 100 K, and isotropic parameters, from X-band spectra of room-temperature solutions. b The
c
[Cu(tach-Et3)Cl2] powder sample displayed rhombic symmetry in its g-values (Figure 3). Α values were calculated from A0 ) 1/3A| + 2/3A .
d 5 mM complex in 50 mM HEPES buffer, pH ) 7.4. e Calculated from the relationship g0 ) 1/3g| + 2/3g . f 2.5 mM complex in 50 mM CAPS
buffer, pH ) 10.1. g Calculated from the relationship g0 ) 1/3(gx + gy + gz).
in solution. Since g| > g > 2.0, the ground-state orbital
L-Cu(II)-aquo and L-Cu-hydroxo species (L ) triamine
ligand) that may be active species in hydrolysis reactions or
other Lewis-acid-catalyzed processes. The goal of these studies
is to understand structure and speciation of Cu(II) complexes
that may lead to mechanistic insight into the hydrolysis process
and more effective hydrolysis agents. Structures of copper
catalyst precursors and active species have been elucidated by
spectroscopic methods with some success in the CuII([9]-
aneN3)2+ 10,44 and CuII(tach-H3)2+ 14 systems for hydrolytic
cleavage of phosphate diesters (particularly bis(p-nitrophenyl)
phosphate (BNPP), a model for nucleotide cleavage). A com-
monly postulated rate-determining step in metal-promoted
phosphate diester or amide cleavage is the transfer of a
coordinated hydroxo group to the respective phosphorus or
amide carbon.
We have observed that a Cu(II) complex of tach-Me3 may
be readily formed in situ at pH 7.4 from aqueous Cu(II) and
tach-Me3. The resulting solutions are active in cleavage of BNPP
at relatively high rates, by a process that is unusual because it
is second-order in concentration of copper complex.15 Therefore,
we wish to understand the structure, bonding, and reactivity
issues of isolated and solution-phase complexes of Cu(II) with
tach-R3. It was also of interest to know the effects of variation
of R in this system. In the Cu(II)-[9]aneN3 system, it has been
observed that addition of i-Pr groups to nitrogen changes the
position of a monomer-dimer equilibrium of the Cu(II)
complexes, presumably through a steric effect.45 It is believed
that only the monomeric Cu(II)-hydroxo species is active in
the catalytic process; therefore, the position of this equilibrium
affects the rate of hydrolysis.7,10
2
2
containing the unpaired electron corresponds to dx -y as
expected for a square-pyramidal structure with a Jahn-Teller
axial elongation.38
Bonding Parameters. The LCAO-MO bonding parameters
of the [Cu(tach-Et3)]2+ in aqueous media were calculated from
the optical transitions and the EPR spin Hamiltonian parameters
(Tables 3 and 4) using the classic equations of Maki and
McGarvey.39 A free Cu(II) ion spin-orbit coupling constant λ
) -868 cm-1, Fermi contact term ko ) 0.43, dx -y ground-
state dipole term P ) 0.036 cm-1, and T(n)nitrogen ) 0.33 and
T(n)oxygen) 0.220 were assumed.40 The small terms in T(n) in
the bonding parameter equations39 reflect the orbital hybridiza-
tion about the donor atoms, and the results are not very sensitive
to the value chosen for T(n); they are frequently ignored in
bonding parameter calculations. The calculation yields R2, â2,
2
2
2
and â1 , the squares of MO coefficients of the metal-centered
2
2
d
x -y , dxz,yz, and dxy orbitals, respectively. R2 represents the
fractional unpaired electron density in the ground state wave
function. Because of uncertainties in such calculations, only the
relative values of the bonding parameters are useful; lower
values of R2, â2, and â12 correspond to increased “covalency.”
The calculated value for R2 ∼ 0.78 indicates moderate in-plane
2
2
σ-bond covalency involving the ground-state dx -y orbital and
is typical of many square pyramidal complexes of copper-
(II).32,33,39,40,41 On the other hand, the computed values of â2 ∼
2
0.92 and â1 ∼ 0.88 are indicative of rather ionic out-of-plane
and in-plane π-bonding involving the dxz,yz and dxy orbitals,
respectively. The ionic character of the π-bonds is consistent
with the replacement of Cl- by H2O in the equatorial plane of
the complex. While chloride can readily participate in π-bond-
ing,32 both water and the donor nitrogen atoms of the tach ligand
lack orbitals with appropriate symmetry for effective π-bonding.
Considerable ionic character in the π-bonding is therefore
expected for [Cu(tach-Et3)(H2O)2]2+, as observed.
The solid-state structure of [Cu(tach-Et3)Br0.8Cl1.2] is a
distorted square-based pyramid in which the two halides occupy
basal positions. Structures of copper(II) triamino dihalide
complexes typically vary from square-based pyramidal to
trigonal-bipyramidal in the solid state.32 For example, complexes
[Cu([n]aneN3)X2] (n ) 9, X ) Cl, Br) possess the square-based
pyramidal geometry, but distortions occur as n increases to 11,
where the shape of [Cu([11]aneN3)Br2] is closer to trigonal-
bipyramidal. All of these complexes are active hydrolysis
catalysts, and there is no observed relationship of coordination
geometry to hydrolytic ability.46
Discussion
Copper complexes with open coordination sites have catalytic
activity in many reactions that are relevant to biology7,42,43 and
organic synthesis.2,3 The present studies focus on the nature of
The displacement of coordinated halide from [Cu(tach-R3)-
Cl2] is important to the catalytic activity of the complexes, for
it provides labile coordination sites for substrate binding.7 We
(38) Pilbrow, J. R. Transition Ion Electron Paramagnetic Resonance;
Clarendon Press: Oxford, U.K., 1990; p 624.
(39) Maki, A. H.; McGarvey, B. R. J. Chem. Phys. 1958, 29, 31.
(40) Kivelson, D.; Neiman, R. J. Chem. Phys. 1961, 35, 149.
(41) Gersmann, H. R.; Swalen, J. D. J. Chem. Phys. 1961, 36, 3221.
(42) Karlin, K. D., Zubieta, J., Eds.; Copper Coordination Chemistry:
Biochemical and Inorganic PerspectiVes; Adenine Press: Guilderland,
NY, 1983.
(44) Deal, K. A.; Hengge, A. C.; Burstyn, J. N. J. Am. Chem. Soc. 1996,
118, 1713.
(45) Burstyn, J. N. Personal communication.
(46) Hegg, E. L.; Mortimore, S. H.; Cheung, C. L.; Huyett, J. E.; Powell,
D. R.; Burstyn, J. N. Inorg. Chem. 1999, 38, 2961.
(43) Comba, P. Coord. Chem. ReV. 2000, in press.

Copper(II) Complexes of N-Alkylated Derivatives
Inorganic Chemistry, Vol. 40, No. 17, 2001 4175
addressed the question of whether the copper-halide bond
hydrolysis could be observed in solution by characterizing the
structure of tach-R3 complexes of Cu(II) in both MeOH and
buffered aqueous phases. Dissolving [Cu(tach-Et3)Br0.8Cl1.2] in
MeOH gives a square-pyramidal complex of the same structure
as the crystalline material, according to UV-vis spectroscopy.
The spectroscopy further demonstrates that in MeOH, all of the
complexes [Cu(tach-R3)Cl2] (R ) Me, Et, n-Pr, CH2-2-thienyl,
CH2-2-furanyl) share the square-bipyramidal structure with a
aneN3)(H2O)(OH)]+.10 Burstyn et al. measured an apparent pKa
of [Cu[9]aneN3]2+(aq) of 7.3 but point out that this value is not
a true pKa because the dimerization equilibrium produces
additional proton donor and acceptor species.7 In the Cu(II)-
tach (i.e., tach-H3) system, Fujii et.al. have proposed that [Cu-
(tach)(H2O)(OH)]+ forms directly from [Cu(tach)(H2O)2]2+at
a pKa of 8.2 ( 0.1 and did not report any evidence for dimeric
species.14 However, the EPR spectra of [Cu(tach-Et3)(H2O)2]2+
-
(aq) are identical at pH 7.4 and 10.1, suggesting that a single
species prevails in this pH range, i.e., that the pKa of coordinated
water in this complex is above 10.1.4 We investigated dimer-
ization of [Cu(tach-Me3)]2+(aq) by quantitative EPR studies at
pH 7.4. The presence of a substantial amount (more than ca.
3%) of an EPR-silent, antiferromagnetically coupled Cu(II)
dimer was ruled out through comparison of the intensity of the
spectrum of [Cu(tach-Me3)]2+(aq) to a Cu(II) standard.15
Because Cu(II) hydroxo species are predominantly dimers or
oligomers in which the hydroxide bridges two metal centers,
the inability of [Cu(tach-Me3)]2+(aq) to dimerize suggests it
assumes the aquo speciation, [Cu(tach-Me3)(H2O)2]2+, as sup-
ported by the data reported herein.
2
2
dx -y ground state, and halide remains bound.
We examined the aqueous-phase reactivity of [Cu(tach-R3)-
X2] in detail with a combined application of EPR spectroscopy
(X- and Q-band) and UV-vis spectroscopy. When [Cu(tach-
Et3)X2] is dissolved in buffered aqueous medium at pH 7.4,
the hydrolysis of copper-halide bonds is observed. An increase
in ligand field strength is noted in the shift of the UV-vis bands
in [Cu(tach-Et3)]2+(aq) relative to the dihalide. Further, the
copper orbital bonding parameters derived for [Cu(tach-Et3)]2+
-
(aq) show rather ionic bonding. Both of these findings are
consistent with replacement of halide by water to afford [Cu-
(tach-Et3)(H2O)2]2+. Further, all of the [Cu(tach-R3)X2] com-
plexes similarly exhibit hydrolysis. The same spectroscopic
parameters are observed for the complex formed in situ from
CuCl2(aq) and tach-Me3‚3HBr. In total, these findings imply
that the solution speciation of [Cu(tach-R3)(H2O)2]2+ is a
reasonable formulation of the catalyst precursors. The EPR data
also indicate a similar aqueous speciation of all the tach-R3-
copper compounds (R ) Me, Et, n-Pr, CH2-furanyl, and CH2-
thienyl) (Table 4).
Variation of ligand bound to Cu(II) is known to affect the
activity of the catalyst in hydrolytic reactions, for example as
demonstrated in the homologous complexes [Cu([n]aneN3)X2]
(n ) 9, 10, 11).46 However, there was little or no effect of
variation of R on either the coordination geometry or the ligand-
field splitting of Cu(II)(tach-R3) complexes in the present study,
even though R varies considerably in steric bulk (R ) Me, Et,
n-Pr, CH2-2-thienyl, and CH2-2-furanyl). However, it was
observed that a ligand with very large steric bulk, tach-
neopentyl3, reacted with Cu(II) to form an intractable blue
material. Possibly in this select case tach-R3 remains in the open
conformation, forming a two-dimensional coordination polymer
with Cu(II).
Conclusion
The complexation chemistry of Cu(II) with tach-R3 has been
defined in the solid and solution (aqueous pH 7.4 and metha-
nolic) phases. All solid- and solution-phase forms of [Cu(tach-
R3)X2] appear to share the square-pyramidal structure. In
aqueous medium at pH 7.4, coordinated halides are replaced
by water to give [Cu(tach-R3)(H2O)2]2+. There is no substantial
effect of variation of R on the ligand field splitting or
coordination geometry in tach-R3 complexes of Cu(II), as
evidenced by the EPR and visible-near-IR spectroscopic data.
Like [9]aneN3, the Cu(II) complex [Cu(tach-Me3)(H2O)2]2+
is an active catalyst in phosphate diester hydrolysis. However,
the tach-Me3 ligand apparently forms a monomeric Cu(II)
complex at pH 7.4, in contrast to [9]aneN3 whose complex is
dimeric. Therefore, the mechanism of this hydrolysis process,
and its relationship to the aqueous speciation of Cu(II) with
tach-R3, promise to be intriguing and will be taken up in the
following paper.15
Acknowledgment. R.P.P. thanks the NIH for support. F.H.L.
thanks the NIH for an STRP fellowship. The authors thank Nole
Whittaker (Laboratory of Analytical Chemistry, NIDDK) for
his efforts in obtaining FAB-MS spectra for this work. We thank
Ms. Ann Przyborowska for the preparation of Figure 2 and Mr.
Neng Ye for preparation of [Cu(tach-thioph3)Cl2]. This work
was supported in part by NIH Grant R37 GM20194 (N.D.C.)
The formation of metal-bound hydroxide has been postulated
in studies of mechanism of hydrolysis by numerous metal ions,
but the findings with the Cu(II)-tach-R3 system differ notably
from other Cu(II)-triamine compounds studied.7,47 In hydrolysis
of BNPP by [Cu([9]aneN3)Cl2], it is believed that Cl is first
displaced by water to afford [Cu([9]aneN3)(H2O)2]2+, which then
dimerizes to [Cu([9]aneN3)(µ-OH)]22+. Then the dimer dissoci-
ates to form a small amount of the active complex [Cu([9]-
Supporting Information Available: X-ray crystallographic data
in CIF format. This material is available free of charge via the Internet
at http://pubs.acs.org.
(47) Pratviel, G.; Bernadou, J.; Meunier, B. AdV. Inorg. Chem. 1998, 45,
251.
IC000829E