Model for the Reduced Schiff Base Intermediate between Amino Acids and Pyridoxal: Copper(II) Complexes of N-(2-Hydroxybenzyl)amino Acids with Nonpolar Side Chains and the Crystal Structures of [Cu(N-(2-hydroxybenzyl)-D,L-alanine)(phen)]·H2O and [Cu(N-(2-hydroxybenzyl)-D,L-alanine)(imidazole)]

Article abstract of DOI:10.1021/ic9606441

Copper(II) complexes with reduced Schiff base ligands of amino acids possessing nonpolar side chains with salicylaldehyde have been synthesized. Ternary complexes with imidazole, 1,10-phenanthroline, and pyridine have been prepared and characterized for N-(2-hydroxybenzyl)-D,L-alanine. The crystal structures of [(N-(2-hydroxybenzyl)-D,L-alanine)(1,10-phenanthroline)Cu(II)] monohydrate ([Cu(SAla)phen]·H₂O) and [(N-(2-hydroxybenzyl)-D,L-alanine)(imidazole)Cu(II)] ([Cu(SAla)Him]), have been determined. [Cu(SAla)phen]·H₂O crystallized in space group P1?, with a = 8.718(2) A?, b = 10.886(3) A?, c = 11.693(2) A?, α = 71.32(2)°, β= 85.27(2)°, γ = 70.21(2)°, and Z = 2. The copper atom is five coordinate, with SAla acting as a tridentate ONO chelator through the carboxylato and phenolato oxygens and the amine nitrogen. The remaining donors are provided by the phen nitrogens. [Cu(SAla)Him] crystallized in space group P2₁/n, with a = 10.353(1) A?, b = 6.714(1) A?, c = 18.769(2) A?, β= 91.71(1)°, and Z = 4. The copper atom is four coordinate, with SAla acting as a tridentate ONO chelator with the neutral imidazole moiety coordinated through nitrogen. In both complexes the ligand has two chiral centers due to the coordination of the N. Molecular mechanics calculations show that unfavorable steric interactions would occur in the nonobserved R,R and S,S diastereomers. Compounds prepared have been characterized by a range of physicochemical techniques. The complexes may serve as stable models for the intermediates in enzymatic amino acid transformations.

Full text of DOI:10.1021/ic9606441

6466
Inorg. Chem. 1996, 35, 6466-6472
Model for the Reduced Schiff Base Intermediate between Amino Acids and Pyridoxal:
Copper(II) Complexes of N-(2-Hydroxybenzyl)amino Acids with Nonpolar Side Chains and
the Crystal Structures of [Cu(N-(2-hydroxybenzyl)-D,L-alanine)(phen)]‚H2O and
[Cu(N-(2-hydroxybenzyl)-D,L-alanine)(imidazole)]
Lip Lin Koh,† John O. Ranford,*,† Ward T. Robinson,‡ Jan O. Svensson,‡
Agnes Lay Choo Tan,§ and Daqing Wu†
Department of Chemistry and Computational Science, National University of Singapore,
Kent Ridge Crescent, Singapore 119260, and Department of Chemistry, University of Canterbury,
Private Bag 4800, Christchurch, New Zealand
ReceiVed May 30, 1996X
Copper(II) complexes with reduced Schiff base ligands of amino acids possessing nonpolar side chains with
salicylaldehyde have been synthesized. Ternary complexes with imidazole, 1,10-phenanthroline, and pyridine
have been prepared and characterized for N-(2-hydroxybenzyl)-D,L-alanine. The crystal structures of [(N-(2-
hydroxybenzyl)-D,L-alanine)(1,10-phenanthroline)Cu(II)] monohydrate ([Cu(SAla)phen]‚H2O) and [(N-(2-hy-
droxybenzyl)-D,L-alanine)(imidazole)Cu(II)] ([Cu(SAla)Him]), have been determined. [Cu(SAla)phen]‚H2O
crystallized in space group P1h, with a ) 8.718(2) Å, b ) 10.886(3) Å, c ) 11.693(2) Å, R ) 71.32(2)°, â )
85.27(2)°, γ ) 70.21(2)°, and Z ) 2. The copper atom is five coordinate, with SAla acting as a tridentate ONO
chelator through the carboxylato and phenolato oxygens and the amine nitrogen. The remaining donors are provided
by the phen nitrogens. [Cu(SAla)Him] crystallized in space group P21/n, with a ) 10.353(1) Å, b ) 6.714(1) Å,
c ) 18.769(2) Å, â ) 91.71(1)°, and Z ) 4. The copper atom is four coordinate, with SAla acting as a tridentate
ONO chelator with the neutral imidazole moiety coordinated through nitrogen. In both complexes the ligand has
two chiral centers due to the coordination of the N. Molecular mechanics calculations show that unfavorable
steric interactions would occur in the nonobserved R,R and S,S diastereomers. Compounds prepared have been
characterized by a range of physicochemical techniques. The complexes may serve as stable models for the
intermediates in enzymatic amino acid transformations.
Introduction
showing the highest activity.10 Research has tended to focus
on copper(II) complexes of N-salicylideneglycine,11 with imi-
dazole, pyrazole, related derivatives, and pyridine ternary
adducts being investigated by ESR12 and for their redox
properties.13
The reaction mechanisms proposed are mainly derived from
model studies of amino acids with pyridoxal or related Schiff
bases and their metal complexes. Spectroscopic evidence shows
that there is often marginal formation of Schiff base in the
absence of a transition metal.6 In fact, a metal is typically
required in model studies both as a template and to stabilize
the resulting product.1c,14 X-ray crystal structures of complexes
Considerable attention has been given to Schiff base adducts
formed between pyridoxal or analogs and amino acids.1,2
Pyridoxal phosphate (PLP) is a cofactor required by many
enzymes catalyzing transformations that amino acids undergo.3
For example, transamination and racemization reactions involve
the formation of an intermediate Schiff base,4 hemoglobin will
react with PLP to form a Schiff base,5 and PLP-dependent
enzymes are involved in R-, â-, and γ-elimination reactions of
amino acids.4,6,7 Both metal ions and H+ increase the rate of
such reactions,8,9 although enzymatic reactions appear to use
only H+.9 Metals do, however, catalyze pyridoxal-mediated
reactions of amino acids in model systems, with copper(II)
(8) (a) Metzler, D. E.; Snell, E. E. J. Am. Chem. Soc. 1952, 74, 979-
983. (b) Longenecker, J. B.; Snell, E. E. J. Am. Chem. Soc. 1957, 79,
142-145. (c) Matsushima, Y.; Martell, A. E. J. Am. Chem. Soc. 1967,
89, 1322-1335. (d) Abbott, E. H.; Martell, A. E. J. Am. Chem. Soc.
1969, 91, 6931-6939.
† Department of Chemistry, National University of Singapore.
‡ University of Canterbury.
§ Computational Science, National University of Singapore.
X Abstract published in AdVance ACS Abstracts, October 1, 1996.
(1) (a) Metzler, D. E.; Ikawa, M.; Snell, E. E. J. Am. Chem. Soc., 1954,
76, 648-652. (b) Mohler, H. R.; Corders, E. H. Biological Chemistry;
Harper and Row: New York, 1971; pp 393. (c) Casella, L.; Gullotti,
M.; Pachioni, G. J. Am. Chem. Soc. 1982, 104, 2386-2396.
(2) Gillard, R. D.; Wootton, R. J. Chem. Soc. B 1970, 364-371.
(3) Stryer, L. Biochemistry; W. H. Freeman and Company: San Francisco,
1981; pp 409-411.
(9) Wagner, M. R.; Walker, F. A. Inorg. Chem. 1983, 22, 3021-3028
and references therein.
(10) (a) Snell, E. E., Braunstein, A. E., Severin, E. S., Torchinsky, Y. M.,
Eds. In Pyridoxal Catalysis: Enzymes and Model Systems; Inter-
science: NewYork, 1968. (b) Holm, R. H. In Inorganic Biochemistry;
Eichhorn, G. L., Ed.; Elsevier: New York, 1973; pp 1137-1167. (c)
Martell, A. E. In Metal Ions In Biological Systems; Sigel, H., Ed.;
Dekker: New York, 1973; Vol. 2, pp 208-263.
(4) Guirard, B. M.; Snell, E. E. ComprehensiVe Biochemistry; Florkin,
M., Stotz, E. H., Eds.; Elsevier: Amsterdam, 1981; pp 138-199.
(5) Mehansho, H.; Henderson, L. M. J. Biol. Chem. 1980, 255, 11901-
11907.
(6) Casella, L.; Guillotti, M. Inorg. Chem. 1983, 22, 2259-2266.
(7) (a) Walsh, C. Annu. ReV. Biochem. 1978, 47, 919-931. (b) Verderas,
J. C.; Floss, H. G. Acc. Chem. Res. 1980, 13, 455-463, and references
therein. (c) Walsh, C.; Pascal, R. A.; Johnson, M.; Raines, R.; Dikshit,
D.; Krantz, A.; Honna, M. Biochemistry 1981, 20, 7509-7519.
(11) (a) Ueki, T.; Ashida, T.; Sasada, Y.; Kakudo, M. Acta Crystallogr.,
Sect. B 1969, 25, 328-335. (b) Ueki, T.; Ashida, T.; Sasada, Y.;
Kakudo, M. Acta Crystallogr. 1967, 22, 872-878. (c) Pavelcik, F.;
Kratsmar-Smogrovic, J.; Svajlenova, O.; Majer, J. Collect. Czech.
Chem. Commun. 1981, 46, 3186-3197.
(12) Plesch, G.; Friebel, C.; Svajlenova, O.; Kratsmar-Smogrovic, J. Inorg.
Chim. Acta 1987, 129, 81-85.
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S0020-1669(96)00644-1 CCC: $12.00 © 1996 American Chemical Society

Cu(II) Complexes of Reduced Schiff Base Ligands
Inorganic Chemistry, Vol. 35, No. 22, 1996 6467
show the ligand to act as a tridentate moiety, coordinating
through the phenolato O, imine N, and carboxyl O.15 With
histidine, the possibility of imidazole complexation also ex-
ists.10,16 The stability of the Schiff base products isolated
depends on factors such as the amino acid side chain polarity,6
the metal, pH, solvent, and temperature.9 However, racemic
complexes are often observed even when optically active amino
acids are employed.2,6,15i Transamination, decomposition, hy-
drolysis of amino acid esters, ester exchange, and oxidation
reactions have been observed as well.2 Casella and Gullotti
found that Schiff bases between amino acids with nonpolar side
chains and 2-formylpyridine were unstable with Zn(II) and Cu-
(II), and only imines of histidine or its methyl ester could be
isolated in reasonable purity.6
classical Cu(II) Schiff base-amino acid systems studied as
models in enzymatic amino acid transformations.
Experimental Section
Ligand Preparations. To a solution of the appropriate amino acid
(10 mmol) in water (10 cm3) containing KOH (0.56 g, 10 mmol) was
added salicylaldehyde (1.20 g, 10 mmol) in ethanol (10 cm3). The
yellow solution was stirred for 30 min at room temperature prior to
cooling in an ice bath. The intermediate Schiff base that had formed
was reduced with an excess of sodium borohydride (0.46 g, 12 mmol)
in water (5 cm3) containing a few drops of sodium hydroxide solution.
The yellow color slowly discharged, and after 10 min the solution was
acidified with concentrated HCl to a pH of 3.5-5.0. The resulting
solid was filtered off, washed with ethanol and then diethyl ether, dried,
and recrystallized from water/ethanol (1:1).
H2SGly: yield, 49%; mp 210-11 °C (lit.20 mp 210-12 °C); 1H NMR
[(CD3)2SO] δ 3.14 (s, 2H), 3.97 (s, 2H), 6.77-6.86 (m, 2H), 7.15-
7.24 (m, 2H). Anal. Calcd(Found): C, 59.7(59.7); H, 6.2(6.1); N,
7.6(7.7).
The problems with ligand instability can be overcome by
reduction of the Schiff base to give an amine, and this presents
interesting possibilities. Ligands are now more flexible and not
constrained to remaining planar. They may also model the
intermediates in transamination reactions where addition of a
nucleophilic solvent across the double bond is thought to occur.2
Although the role of copper has been stressed, to date only
solution studies measuring the stability constants of nonisolated
complexes have been determined for chiral ligands.17 As it has
been suggested that ternary adduct formation may play a role
in the in ViVo activity of complexes through binding of the
species to biological ligands, it is of interest to investigate these.
The only crystal structures for this ligand type appear to be the
cobalt ternary complex18 [R-N-(o-hydroxybenzyl)-L-histidinato]-
(L-alaninato)cobalt(III) dihydrate ([Co(SHis)Ala]‚2H2O) and the
Gly derivatives19 [{Cu(SGly)}2(H2O)]‚H2O and [Co(NH3)6]-
[Co(SGly)2]2Cl.
1
H2SAla: yield, 40%; mp 241-2 °C; H NMR [(CD3)2SO] δ 1.30
(d, 3H, J ) 7.1 Hz), 3.24 (q, 1H, J ) 7.1 Hz), 3.88 and 4.00 (AB
system, 2H, JAB ) 13.5 Hz), 6.76-6.83 (m, 2H), 7.14-7.24 (m, 2H).
Anal. Calcd(Found): C, 61.6(61.5); H, 6.6(6.7); N, 7.2(7.2).
H2SLeu‚0.5H2O: yield, 57%; mp 222-3 °C; 1H NMR [(CD3)2SO]
δ 0.83 (d, 3H, J ) 6.6 Hz), 0.87 (d, 3H, J ) 6.6 Hz), 1.54-1.42 (m,
1H), 1.81-1.73 (m, 2H), 3.15 (t, 1H, J ) 7.1 Hz), 3.78 and 3.94 (AB
system, 2H, JAB ) 13.6 Hz), 6.75-6.80 (m, 2H), 7.12-7.20 (m, 2H).
Anal. Calcd(Found): C, 64.1(64.1); H, 8.0(8.2); N, 5.6(5.8).
1
H2SIle: yield, 56%; mp 219-21 °C; H NMR [(CD3)2SO] δ 0.82
(t, 3H, J ) 7.4 Hz), 0.86 (d, 3H, J ) 6.8 Hz), 1.36 (m, 2H), 1.71 (m,
1H), 3.02 (d, 1H, J ) 3.8 Hz), 3.71 and 3.92 (AB system, 2H, JAB
)
13.6 Hz), 6.73-6.78 (m, 2H), 7.09-7.17 (m, 2H). Anal. Calcd-
(Found): C, 65.7(65.8); H, 8.0(8.0); N, 5.9(5.9).
1
H2SPhe‚H2O: yield, 86%; mp 211-2 °C; H NMR [(CD3)2SO] δ
In this paper we have prepared reduced Schiff base ligands
of salicylaldehyde with glycine (H2SGly, R ) H), alanine
(H2SAla, R ) CH3), leucine [H2SLeu, R ) CH2CH(CH3)2],
isoleucine [H2SIle, R ) CH(CH3)CH2CH3], phenylalanine
(H2SPhe, R ) CH2C6H5), and glycine methyl ester (HSGlyMe).
2.97 (d, 2H, J ) 6.9 Hz), 3.42 (t, 1H, J ) 6.9 Hz), 3.61 and 3.79 (AB
system, 2H, JAB ) 13.6 Hz), 6.70-6.74 (m, 2H), 6.99-7.11 (m, 2H),
7.21-7.31 (m, 5H). Anal. Calcd(Found): C, 66.8(65.8); H, 6.2(6.6);
N, 5.0(4.8).
N-(2-Hydroxybenzyl)glycine Methyl Ester (HSGlyMe). A solu-
tion of salicylaldehyde (0.90 cm3, 7.5 mmol) and glycine methyl
ester‚HCl (0.95 g, 7.5 mmol) in methanol (15 cm3) with methanolic
KOH (1 M, 7.5 cm3) was mixed and stirred at room temperature for
30 min. The reaction was then cooled in an ice bath, and sodium
borohydride (0.46 g, 12 mmol) was added in several portions. After
15 min of stirring the pH was adjusted to 5 with acetic acid. The solvent
was evaporated under reduced pressure and water was added. After
extraction with dichloromethane, the organic extracts were washed with
saturated aqueous sodium hydrogen carbonate and then with water.
The organic phase was dried over anhydrous sodium sulfate and the
solvent evaporated. The residue was chromatographed on silica gel
using ethyl acetate/ethanol (9:1) as eluent to afford the compound:
Binary and ternary copper(II) complexes of these have been
isolated and characterized, and the single-crystal X-ray structures
of the ternary adducts [Cu(SAla)phen]‚H2O and [Cu(SAla)Him]
have been determined. Molecular mechanics calculations have
been used to show the preference for the S,R and R,S configura-
tions at the CR and amine N centers found in the complexed
ligands. We highlight the differences between the structural
and spectroscopic properties of our complexes and related
1
yield, 716 mg, 49%; mp 79-80 °C; H NMR [(CD3)2SO] δ 3.36 (s,
2H), 3.63 (s, 3H), 3.75 (s, 2H), 6.70-6.75 (m, 2H), 7.04-7.10 (m,
2H). Anal. Calcd(Found): C, 61.8(61.5); H, 6.8(6.7); N, 7.0(7.2).
Complex Preparations. As the general procedure for preparing
binary complexes was the same, the first example given is generally
applicable with procedures different from those listed subsequently.
Yields ranged from 44 to 70%.
[Cu(HSGly)2]‚0.5H2O (1). Addition of a solution of H2SGly (181
mg, 1.00 mmol) and LiOH (24 mg, 1.00 mmol) in water (20 cm3) to
copper(II) acetate monohydrate (100 mg, 0.50 mmol) in ethanol (10
cm3) gave a light green product. This was filtered off and washed
with water, ethanol, and diethyl ether before drying in Vacuo. Yield:
134 mg, 74%.
[{Cu(SGly)}2]‚2H2O (2). Copper(II) acetate monohydrate (430 mg,
2.00 mmol) in ethanol (15 cm3) was added to a previously filtered
solution of H2SGly (181 mg, 1.00 mmol) in hot water (20 cm3). The
precipitate was filtered off and washed several times with water, ethanol,
and then diethyl ether before drying in Vacuo. Yield: 106 mg, 46%.
(15) (a) Dawes, H. M.; Waters, J. M.; Waters, T. N. Inorg. Chim. Acta
1982, 66, 29-36. (b) Bkouche-Waksman, I.; Barbe, J. M.; Kvick, A.
Acta Crystallogr. 1988, B44, 595-601. (c) Ha¨ma¨la¨inen, R.; Turpeinen,
U. Acta Crystallogr. 1985, C41, 1726-1728. (d) Korhonen, K.;
Ha¨ma¨la¨inen, R.; Turpeinen, U. Acta Crystallogr. 1984, C40, 1175-
1177. (e) Nakajima, K.; Kojima, M.; Foriumi, K.; Saito, K.; Fujita, J.
Bull. Chem. Soc. Jpn. 1989, 62, 760-767. (f) Ha¨ma¨la¨inen, R.;
Turpeinen, U. Acta Chem. Scand. 1989, 43, 15-18. (g) Nassimbeni,
L. R.; Percy, G. C.; Rodgers, A. L. Acta Crystallogr. 1976, B32, 1252-
1256. (h) Smith, F. E.; Hynes, R. C.; Ang, T. T.; Khoo, L. E.; Eng,
G. Can. J. Chem. 1992, 70, 1114-1120. (i) Kettmann, V.; Fresˇova´,
E. Acta Crystallogr. 1993, C49, 1932-1934.
(16) Ranford, J. D.; Robinson, W. T.; Svensson, J. O.; Wu, D. Q.
Manuscript in preparation.
(17) Patel, P.; Bhattacharya, P. K. Indian J. Chem. 1993, 32A, 506-510.
(18) Voss, K. E.; Angelici, R. J.; Jacobson, R. A. Inorg. Chem. 1978, 17,
1922-1925.
(19) Chen, M. Q.; Xu, J. X.; Zhang, H. L. Jiegou Huaxue 1991, 10, 1-9.
(20) Wilson, J. G. Aust. J. Chem. 1990, 43, 1283-1289.

6468 Inorganic Chemistry, Vol. 35, No. 22, 1996
Koh et al.
[Cu(SAla)phen]‚H2O (5) and [Cu(SAla)Him] (7). To the royal
blue solution formed from copper(II) acetate monohydrate (200 mg,
1.00 mmol) in ethanol (15 cm3) and imidazole (146 mg, 2 mmol) or
1,10-phenanthroline (180 mg, 1.00 mmol) in ethanol (10 cm3) was
added a filtered solution of H2SAla (200 mg, 1.00 mmol) in water (20
cm3) with KOH (1.0 cm3, 1 M). The dark green solutions were stirred
for 2 h and then filtered and left for several days, after which time
crystalline solids had formed that were filtered off, washed with ethanol,
and dried in Vacuo. Yields: 5, 259 mg, 57.0%; 7, 177 mg, 53.8%.
[Cu(SAla)py]‚H2O (6). Upon gentle heating of [Cu(HSAla)2] (487
mg, 1.00 mmol) in excess pyridine (10 cm3) the complex dissolved.
The filtered solution was left to evaporate at room temperature and
after 2 weeks dark green crystals were collected and dried in Vacuo.
Yield: 237 mg, 67%.
of higher lattice symmetry. Data were collected in ω-scan mode. From
a total of 4811 reflections in the range 2 e θ e 22.5° (1710 unique),
4402 satisfied the I > 2(I) criterion of observability. Data were
corrected for Lorentz and polarization effects and for a decay of 4.3%
of the three periodically measured reference reflections (3 1 0, 1 4 1,
6 1 -2), and a face-indexed absorption correction was applied (range
of transmission coefficients 0.572-0.769).
(c) Structural Analysis. The structure was solved by automated
direct methods (SHELXS90).21 Refinement, based on F2, was carried
out by full-matrix least-squares techniques (SHELXL93).22 Hydrogen
atoms were included in the refinement in calculated positions, riding
on their carrier atoms. All non-hydrogen atoms were refined with
anisotropic thermal displacement parameters; the hydrogen thermal
displacement parameters were fixed at 1.2 and 1.5 times the equivalent
isotropic thermal displacement parameters of their internal and terminal
carrier atoms, respectively. Convergence was reached at RF ) 0.0348
[for 4402 reflections with I > 2σ(I)], RwF2 ) 0.0922 (for all data),
[{Cu(SIle)}2] (9). To a filtered solution of H2SIle (245 mg, 1.03
mmol) and LiOH (25 mg, 1.05 mmol) in hot water (25 cm3) was added
copper(II) acetate monohydrate (200 mg, 1.00 mmol) in ethanol (10
cm3). The resulting light green powder was filtered off and washed
with water before drying in Vacuo. Complexes 11 and 13 were prepared
similarly. Yields ranged from 48 to 80%.
2
and S ) 1.132 based on Fo , for 183 parameters. A final difference
Fourier map showed no residual electron density outside -0.706 and
0.905 (near Cu) e Å-3. Positional parameters are listed in Table 3.
Neutral atom scattering factors and absorption coefficients were taken
from International Tables for Crystallography, Volume C, 1992.
[Cu(SGlyMe)2] (14). To a solution of HSGlyMe (310 mg, 1.50
mmol) in methanol (15 cm3) was added a solution of copper(II) acetate
monohydrate (157 mg, 0.75 mmol) in methanol (5 cm3). The mixture
was stirred for 1 h. The dirty green precipitate was filtered off and
washed with methanol prior to drying in Vacuo. Yield: 300 mg, 66.4%.
Materials. Reagents were purchased from the following suppliers:
amino acids, Sigma; salicylaldehyde, copper(II) acetate, glycine methyl
ester hydrochloride, imidazole, and 2,2′-bipyridyl, Fluka; 1,10-phenan-
throline monohydrate, Aldrich. Solvents were purified by standard
procedures.
Physical Measurement. The electronic transmittance spectra were
recorded on a Shimadzu UV-1601 UV-vis spectrophotometer using
Nujol mulls and in DMSO solution. Microanalyses (Table 1) were
performed by the microanalysis unit at the National University of
Singapore. Room-temperature magnetic susceptibility measurements
were carried out at on a Johnson-Matthey Magnetic Susceptibility
balance with Hg[Co(SCN)4] as standard. Corrections for diamagnetism
were made using Pascal’s constants.23 Conductance measurements were
made using a Kyoto Electronics CM-115 conductivity meter with a
X-ray Crystallography. 1. [Cu(SAla)phen]‚H2O. (a) Crystal
Data. C22H21CuN3O4: triclinic, space group P1h; a ) 8.718(2) Å, b )
10.886(3) Å, c ) 11.693(2) Å, R ) 71.32(2)°, â ) 85.27(2)°, γ )
70.21(2)°; V ) 988.8(4) Å3, Z ) 2; M ) 455.0 g mol-1; Dc ) 1.582
g cm-3; absorption coefficient 1.140 mm-1; λ ) 0.710 73 Å; F(000)
) 470; crystal dimensions 0.35 × 0.20 × 0.20 mm.
1
Kyoto Electronics conductivity cell on ca. 1 mM solutions. The H
NMR spectra were recorded on a Bruker ACF 300 spectrometer
operating in the quadrature mode at 300 MHz for solutions in DMSO-
d6 with SiMe4 as internal standard. Infrared spectra were recorded on
a Shimadzu IR-470 infrared spectrophotometer as KBr disks in the
range 4000-400 cm-1
.
(b) Measurements. Refined unit-cell parameters were found by
centering 19 reflections, in the range 20° < 2φ < 40°, on a Siemens
R3m/V diffractometer. A total of 3753 data points was measured, of
which 3499 were unique, in the range 3.5 e 2φ e 50.0° with graphite-
monochromated Mo KR radiation (λ ) 0.710 73 Å) and index ranges
0 e h e 10, -12 e k e 12, and -13 e l e 13 with a variable scan
rate of 3.00-29.30° min-1. Of these, 3091 reflections had F > 4.0
σ(F) and were considered to be observed for the purposes of structure
solution and refinement. Two standard reflections were monitored
every 98 reflections and showed no significant loss during data
collection. The data were corrected for Lorentz and polarization effects,
and a semiempirical absorption correction by psi scan was applied.
Molecular Mechanics Calculations. Molecular modeling, visual-
ization and analysis were performed using SYBIL24 running on a Silicon
Graphics Onyx computer. The Tripos force field (6.0),24 including the
expanded metal parameter set (metal.tpd), was employed with the
following modifications to the default parameter set for 7. To reproduce
the experimental square planar Cu(II), angles about Cu were set to 90°
and 180° with the default force constant of 0.02 kcal mol-1 deg-2, the
out-of-plane bend was set to 230 kcal mol-1 deg-2 and the following
torsions were defined: C11-N2-Cu-O12, 1.33°, 600 kcal mol-1
deg-2; N2-Cu-O12-C1, 180°, 0.80 kcal mol-1 deg-2; Cu-O12-
C1-O11, 180°, 0.004 kcal mol-1 deg-2; N2-Cu-O6-C6, 180°, 0.004
kcal mol-1 deg-2. The Cu-N distances from the crystal structure were
employed with an average Cu-O distance of 1.94 Å together with a
Cu-ligand force constant of 600 kcal mol-1 Å-2. The imidazole was
treated as an aggregate. For 5, the complex was treated as an
octahedron with a lone pair, with Cu bond distances as in the X-ray
structure and a force constant of 600 kcal mol-1 Å-2. Angles about
the Cu ion were as observed in the X-ray structure with a force constant
of 0.04 kcal mol-1 deg-2, except for the phen bite angle which was set
at 400 kcal mol-1 deg-2. The following torsions were set, by using
the observed bond angles unless indicated otherwise, to best reproduce
(c) Structural Analysis. The structure was solved by direct
methods. All non-hydrogen atoms were refined anisotropically.
Hydrogen atoms attached to Ow were located from difference maps.
The other hydrogen atoms were put at calculated positions with a fixed
distance (0.960 Å) from carbon atoms and were assigned fixed thermal
parameters. A total of 272 parameters was refined. The function
minimized during full-matrix least-squares refinement was ∑w|Fo -
2
Fc| where w-1 ) σ2(F) + 0.0029F2, giving R ) 0.0317 and Rw
)
0.0537. The final Fourier difference map was featureless, with a largest
peak of 0.33 e Å-3. Positional parameters are listed in Table 2. All
calculations were performed using the Siemens SHELXTL PLUS-PC
program package.
the X-ray structure observed: O6-Cu-N2-C20, 400 kcal mol-1 deg-2
;
O6-Cu-N3-C21, 400 kcal mol-1 deg-2. N3-Cu-N1-C4, 0.2 kcal
mol-1 deg-2; Cu-O12-C1-O11, 180°, 0.004 kcal mol-1 deg-2; N2-
Cu-O12-C1, 180°, 0.002 kcal mol-1 deg-2; N2-Cu-O6-C6, 155.0°,
2. [Cu(SAla)Him]. (a) Crystal Data. C13H15CuN3O3: monoclinic,
space group P21/n; a ) 10.353(1) Å, b ) 6.714(1) Å, c ) 18.769(2)
Å, â ) 91.71(1)°, V ) 1304.1(3) Å3, Z ) 4; M ) 324.8 g mol-1; Dc
) 1.654 g cm-3; absorption coefficient 1.686 mm-1; λ ) 0.710 73 Å;
F(000) ) 668; crystal dimensions 0.40 × 0.36 × 0.16 mm; temperature
of measurement ) 188(2) K.
(b) Measurements. Intensity data were collected for a dark blue,
block-shaped crystal at 188 K on a Siemens P4 diffractometer. Final
lattice parameters were determined by least-squares treatment, using
the setting angles of 27 well-centered reflections in the range 10.3 e
2θ e 24.9°. The unit cell parameters were checked for the presence
0.002 kcal mol-1 deg-2
.
(21) Sheldrick, G. M., University of Go¨ttingen, 1990.
(22) Sheldrick, G. M., University of Go¨ttingen, 1993.
(23) Earnshaw, A. Introduction to Magnetochemistry; Academic Press:
London, 1968; p 48.
(24) (a) SYBIL 6.2, Tripos Inc., 1699 South Hanley Road, St. Louis, MO
63144. (b) Clarke, M.; Cramer, R. D.; Van Openbosch, N. J. Comput.
Chem. 1989, 10, 982-1012.

Cu(II) Complexes of Reduced Schiff Base Ligands
Inorganic Chemistry, Vol. 35, No. 22, 1996 6469
Table 1. Elemental Analysis, Colors, and Effective Magnetic Moments of Complexes
analysis (%)a
complex
color
C
H
N
µeffb/µB
1
2
3
4
5
6
7
8
9
10
11
12
13
14
[Cu(HSGly)2]‚0.5H2O
[{Cu(SGly)}2]‚2H2O
[Cu(HSAla)2]‚2H2O
[{Cu(SAla)}2]‚2H2O
[Cu(SAla)phen]‚H2O
[Cu(SAla)py]‚H2O
[Cu(SAla)Him]
[Cu(HSIle)2]‚2.5H2O
[{Cu(SIle)}2]
[Cu(HSLeu)2]‚H2O
[{Cu(SLeu)}2]‚H2O
[Cu(HSPhe)2]‚3H2O
[{Cu(SPhe)}2]
light green
green
light blue
green
dark green
green
dark green
green
light green
green
turquoise
green
blue
green brown
50.2(49.9)
41.3(41.5)
53.1(53.1)
40.6(41.0)
58.0(58.0)
50.9(50.9)
47.4(48.0)
54.0(53.8)
52.0(52.3)
56.3(56.4)
48.2(47.9)
58.5(58.4)
57.7(57.7)
53.1(53.1)
4.9(4.9)
4.0(4.3)
4.9(5.3)
4.7(5.1)
4.5(4.6)
5.2(5.1)
4.7(4.7)
5.7(5.7)
5.7(5.7)
6.4(6.9)
5.5(6.2)
5.4(5.8)
4.8(4.5)
4.9(5.3)
6.5(6.5)
5.4(5.4)
6.0(6.2)
4.8(4.8)
9.0(9.2)
8.0(7.9)
12.9(12.9)
4.8(4.8)
4.7(4.7)
5.0(5.1)
4.2(4.3)
4.3(4.2)
4.2(4.2)
6.0(6.2)
2.23
1.55
1.95
1.31
1.79
1.83
1.79
2.07
1.84
2.24
1.57
1.99
1.78
1.87
[Cu(SGlyMe)2]
a Calculated values are given in parentheses. b At 293 K per metal ion.
Table 2. Atomic Coordinates (×104) and Equivalent Isotropic
Displacement Coefficients (Å2 × 103) for [Cu(SAla)phen]‚H2O (5)
with Estimated Standard Deviations in Parentheses
Table 3. Atomic Coordinates (×104) and Equivalent Isotropic
Displacement Coefficients (Å2 × 103) for [Cu(SAla)Him] (7) with
Estimated Standard Deviations in Parentheses
x
y
z
U(eq)
x
y
z
U(eq)
Cu
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
725(1)
-1397(3)
-1296(3)
-1710(4)
472(3)
2125(1)
1112(3)
2319(3)
2218(3)
3762(3)
3976(3)
3954(2)
4260(3)
4629(3)
4632(3)
4306(3)
-247(3)
-1405(3)
-1921(3)
-1241(3)
-1653(3)
-922(3)
291(3)
1110(3)
2251(3)
2564(3)
695(2)
-64(3)
2433(2)
411(2)
1824(2)
352(2)
1013(2)
3684(2)
4584(2)
2234(1)
3833(2)
4202(2)
5501(3)
3874(2)
3365(2)
2174(2)
1679(3)
2335(3)
3501(3)
4005(3)
3160(3)
3091(3)
2175(3)
1268(3)
222(3)
-649(3)
-559(2)
-1467(2)
-1313(2)
-251(2)
466(2)
1398(2)
3851(2)
2333(2)
617(2)
31(1)
38(1)
38(1)
52(1)
38(1)
35(1)
33(1)
40(1)
51(1)
53(1)
44(1)
46(1)
55(1)
52(1)
40(1)
50(1)
47(1)
37(1)
45(1)
42(1)
38(1)
30(1)
33(1)
32(1)
36(1)
31(1)
50(1)
44(1)
36(1)
53(1)
Cu
1442(1)
3071(2)
-244(2)
-2195(2)
550(3)
2477(3)
2235(3)
-1142(4)
-876(3)
-1600(4)
974(3)
2340(4)
3299(4)
4552(4)
4859(4)
3938(4)
2678(4)
1647(4)
3678(4)
3536(3)
1272(1)
1750(4)
721(4)
-451(4)
711(5)
1250(5)
1499(5)
252(6)
3186(1)
2751(1)
3584(1)
3286(3)
2262(2)
5295(2)
4136(2)
3129(2)
2355(2)
1823(2)
1700(2)
1518(2)
2061(2)
1860(2)
1153(2)
622(2)
14(1)
16(1)
18(1)
21(1)
14(1)
18(1)
14(1)
16(1)
17(1)
24(1)
18(1)
15(1)
14(1)
16(1)
18(1)
19(1)
17(1)
16(1)
21(1)
18(1)
O(6)
O(12)
O(11)
N(1)
N(3)
N(2)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
C(13)
2049(3)
2445(3)
3835(3)
4788(4)
4398(4)
3035(4)
4324(3)
5596(4)
5621(4)
4384(3)
4354(4)
3198(4)
1928(3)
718(4)
-454(4)
-430(3)
1891(3)
3149(3)
354(3)
3097(3)
701(3)
C(8)
C(9)
722(6)
-585(7)
2081(6)
1689(5)
1471(5)
1000(6)
856(6)
1162(6)
1525(6)
1256(5)
1497(6)
1653(6)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
C(20)
C(21)
C(22)
N(1)
N(3)
N(2)
O(11)
O(12)
O(6)
Ow
812(2)
4741(2)
5031(2)
4320(2)
of such ligand preparations does not show any apparent pattern
to when racemization occurs, although the presence of a metal
may favor the retention of chirality by acting as a template.
Addition of copper(II) salt to ligand in aqueous solution led
to the precipitation of the binary complexes. The ternary
adducts [Cu(SAla)phen]‚H2O (5) and [Cu(SAla)Him] (7) were
prepared by adding the nitrogen base, either phen or Him, to
the copper salt followed by addition of the H2SAla ligand.
Alteration of the order of addition of reagents had no effect on
the product. However, when [Cu(HSAla)2]‚2H2O (3) is treated
with excess pyridine, the ternary adduct [Cu(SAla)py]‚H2O (6)
in which one ligand has been displaced and the remaining
deprotonated was isolated. All complexes are stable at room
temperature. Microanalytical data are listed in Table 1 together
with complex colors and magnetic moments. The presence of
hydrated water was confirmed by a broad absorption at ca. 3450
cm-1 in infrared spectra for the ligands and complexes.
However, the spectra were complicated with numerous bands,
and assignments based on these therefore were not undertaken.
Crystal Structure of [Cu(SAla)phen]‚H2O (5). A thermal
ellipsoid diagram giving the unique atom labeling is shown in
Figure 1. Selected bond distance and angle data are given in
-2131(3)
-685(3)
1489(2)
1829(3)
4431(2)
2842(2)
1513(2)
8996(2)
Results and Discussion
To overcome the general problems of ligand instability for
Schiff bases of amino acids, and to introduce greater ligand
flexibility and model the proton-shifted intermediate of tran-
samination reactions, an in situ reduction was carried out on
the salicylaldehyde-amino acid mixture. The conditions
employed gave satisfactory elemental analyses for the ligands;
however, they were isolated as racemates. This was unexpected
as the conditions employed were similar to those previously
used to isolate optically active material, namely, the reaction
temperature was kept to 30 °C with a reaction time of 30 min.
Optically active Schiff bases between, for example, salicylal-
dehyde or pyridoxal and Ala, Val, Phe, and His have been
reported25 by refluxing the reagents for 2 h, and H2Sal-L-His
was prepared by a procedure analogous to ours.18,26 A survey
(26) (a) Meiske, L. A.; Jacobson, R. A.; Angelici, R. J. Inorg. Chem. 1980,
19, 2028-2034. (b) Meiske, L. A.; Angelici, R. J. Inorg. Chem. 1980,
19, 3783-3789.
(25) Casella, L.; Guillotti, M. Inorg. Chem. 1986, 25, 1293-1303.

6470 Inorganic Chemistry, Vol. 35, No. 22, 1996
Koh et al.
Figure 1. Structure of [Cu(SAla)phen]‚H2O (5) showing the numbering
scheme (hydrogen atoms are not labeled for clarity).
Figure 2. Structure of [Cu(SAla)Him] (7) showing the numbering
scheme (hydrogen atoms are not labeled for clarity).
Tables 4 and 5, respectively. The structure consists of mono-
meric units with the copper center as an approximate square
pyramidal geometry. The four basal positions are occupied by
the tridentate, dianionic SAla ligand, which furnishes an ONO
donor set, with the fourth position occupied by a phen N. The
coordination sphere is completed by the remaining phen N
binding at the apex. The phen is planar and lies at an angle of
84° to the plane of best fit through the tridentate SAla ligand.
To our knowledge, this is the first structure of this ligand.
In addition, it is the only one of copper with a reduced chiral
amino acid Schiff base. The only others for this general class
of ligand are Co(III) in [R-N-(o-hydroxybenzyl)-L-histidinato]-
(L-alaninato)cobalt(III) dihydrate18 ([Co(SalHis)Ala]‚2H2O) and
the complexes of (o-hydroxybenzyl)glycinate (H2SGly)19 ([{Cu-
(SGly)}2(H2O)]‚H2O and [Co(NH3)6][Co(SGly)2]2Cl). The in-
plane distances for 5 therefore will be compared with those of
[{Cu(SGly)}2(H2O)]‚H2O and the averages of those for Cu(II)
with amino acid-salicylidene complexes.15 The Cu-amine
distance [Cu-N(1), 2.007(2) Å] in 5 is significantly longer than
the Cu-imine length observed [1.939(15) Å]. The bond to the
phenolato O [Cu-O(6), 1.947(2) Å] is also longer (1.912 Å).
The decrease in conjugation upon reducing the imine will result
in reduced charge delocalization, which is seen in the longer
bond distances. The distance to the carboxylato O [Cu-O(12),
1.948(2) Å] is not significantly different from that in the imine
structures (1.956 Å). The remaining in-plane site is to the phen
[Cu-N(2), 2.022(2) Å]. The best-fit least-squares plane through
the four basal and Cu atoms shows a small tetrahedral distortion
with an average distance from the plane of 0.104 Å. The Cu
atom lies 0.167 Å out of the plane toward the apex of the
pyramid, as is seen in salicylidene-amino acid structures.11ab,15i,27
The final bond to the Cu atom, completing the coordination
sphere, is to the remaining phen nitrogen [Cu-N(3), 2.249(2)
Å] in an axial position, with this increase in distance being
typical for Jahn-Teller-distorted Cu(II).27
centered about N(1) are consistent with an sp3 tetrahedral N
and are similar to those for Co(SalHis)Ala.18 The exception is
C(4)-N(1)-C(2), which is 112.0(2)° for 5 but 117.3(5)° for
Co(SalHis)Ala. This is probably due to the histidine imidazole
coordination in the latter structure, giving a tetradentate ligand
and forcing the angular changes about the chiral center C(2).
The observed difference between the coordinated and uncoor-
dinated carboxylate oxygens is typical for such structures.15a,c-g,18
In addition to the asymmetric center in the ligand at atom
C(2) (R as shown in Figure 1), the coordination of the SAla
ligand to the metal ion gives rise to an asymmetric secondary
nitrogen atom N(1), which has the S absolute configuration in
Figure 1. The observed trans configuration should result in less
steric interactions. The P1h space group means that the other
molecule in the unit cell, related by an inversion center, has
opposite chirality for both C(2) and N(1) and the two molecules
therefore are diastereoisomers.
Intermolecular hydrogen bonds through the waters of crystal-
lization occur in the crystal. The water oxygen atom (Ow) is
within hydrogen-bonding distance (2.813 Å) of the phenolate
oxygen O6 and is 2.855 Å from O6 in symmetry-related
molecules. One other apparent hydrogen-bonding interaction
involves direct interaction of the alaninate carboxyl oxygen O11
with nitrogen N1 of an adjacent molecule (3.01 Å).
Crystal Structure of [Cu(SAla)Him] (7). A thermal el-
lipsoid diagram giving the unique atom labeling is shown in
Figure 2. Selected bond distance and angle data are given in
Tables 4 and 5, respectively. The structure consists of mono-
meric units with the copper center in a square planar geometry.
The four positions are occupied by the tridentate, dianionic SAla
ligand with the final position taken by an imidazole N. The
closest axial approaches to the Cu are at ca. 3.3 Å to C(6) and
C(7) from symmetry-related molecules.
The successful in situ reduction of the imine is evident from
the N(1)-C(4) distance [1.493(4) Å] when compared with the
average distance seen for related salicylidene ligands with Cu-
(II) (1.27-1.30 Å). Further, the distances for C(4)-C(5)
[1.514(4) Å] and N(1)-C(2) [1.498(4) Å] are typical of single
bonds, being significantly longer than those of imine com-
plexes15 and indicating the loss of conjugation. The angles
The average in-plane bonding distance in 7 is significantly
shorter than that for 5, with the stronger bonding compensating
for the lower coordination number in 7. The best-fit least-
squares plane through the four basal and Cu atoms shows these
atoms to be nearly coplanar. The O(12)-Cu-O(6) angle of
177.09(9)° is nearly linear and considerably greater than the
162.4(1)° seen in 5, where steric constraints of the chelated phen
and the adoption of a square pyramidal geometry have forced
the oxygen donors out of the plane. Effects of this are seen for
Cu-O(6)-C(6), where the angle has opened up by 5.6° in 7,
and around the chiral N(1), where the Cu-N(1)-C(4) angle
has decreased by 3.2° and Cu-N(1)-C(2) has increased 4.5°
relative to 5. Bond lengths within the dianionic SAla ligand in
(27) (a) Clifford, F.; Counihan, E.; Fitzgerald, W.; Seff, K.; Simmons, C.;
Tyagi, S.; Hathaway, B. J. Chem. Soc., Chem. Commun. 1982, 196-
201. (b) Castro, R.; Dura´n, M. L.; Garcia-Va´zquez, J. A.; Romero, J.;
Sousa, A.; Castin˜eiras, A.; Hiller W.; Stra¨hle, J. Polyhedron 1992,
11, 1195-1200. (c) Anderson, O. P. J. Chem. Soc., Dalton Trans.
1973, 1237-1241. (d) Rajender-Reddy, K.; Rajasekharan, M. V.
Polyhedron 1994, 13, 765-769.

Cu(II) Complexes of Reduced Schiff Base Ligands
Inorganic Chemistry, Vol. 35, No. 22, 1996 6471
Table 4. Selected Bond Lengths (Å) for [Cu(SAla)phen]‚H2O (5)
and [Cu(SAla)Him] (7) with Estimated Standard Deviations in
Parentheses
Table 5. Selected Bond Angles (deg) for [Cu(SAla)phen]‚H2O (5)
and [Cu(SAla)Him] (7) with Estimated Standard Deviations in
Parentheses
5
7
5
7
Cu-N(1)
2.007(2)
2.249(2)
2.022(2)
1.948(2)
1.947(2)
1.539(5)
1.223(4)
1.286(3)
1.511(4)
1.498(4)
1.514(4)
1.493(4)
1.412(4)
1.385(5)
1.396(4)
1.340(4)
1.404(5)
1.379(5)
1.385(5)
1.976(3)
N(1)-Cu-N(3)
N(1)-Cu-N(2)
N(3)-Cu-N(2)
N(1)-Cu-O(12)
N(3)-Cu-O(12)
N(2)-Cu-O(12)
N(1)-Cu-O(6)
N(3)-Cu-O(6)
N(2)-Cu-O(6)
O(12)-Cu-O(6)
C(2)-C(1)-O(11)
C(2)-C(1)-O(12)
108.5(1)
170.3(1)
78.2(1)
83.2(1)
98.3(1)
89.0(1)
94.2(1)
99.0(1)
91.5(1)
162.4(1)
121.7(3)
113.8(3)
Cu-N(3)
172.67(13)
84.23(11)
Cu-N(2)
Cu-O(12)
Cu-O(6)
1.947(3)
1.954(2)
1.923(2)
1.521(5)
1.232(4)
1.282(4)
1.511(5)
1.492(5)
1.488(5)
1.477(5)
1.410(5)
1.384(5)
1.398(5)
1.336(4)
1.377(5)
1.374(5)
1.385(6)
1.314(5)
1.384(5)
1.328(5)
1.362(5)
1.341(5)
C(1)-C(2)
C(1)-O(11)
C(1)-O(12)
C(2)-C(3)
C(2)-N(1)
C(4)-C(5)
C(4)-N(1)
C(5)-C(6)
C(5)-C(10)
C(6)-C(7)
C(6)-O(6)
C(7)-C(8)
C(8)-C(9)
C(9)-C(10)
91.27(11)
92.98(11)
91.42(11)
177.09(9)
119.7(3)
115.9(3)
124.4(3)
114.2(3)
108.5(3)
113.2(3)
111.0(3)
120.4(3)
120.2(3)
119.4(3)
117.9(3)
123.1(3)
119.0(3)
121.2(3)
120.9(3)
118.5(3)
121.9(4)
109.6(2)
111.5(2)
113.3(3)
O(11)-C(1)-O(12) 124.4(3)
C(1)-C(2)-C(3)
C(1)-C(2)-N(1)
C(3)-C(2)-N(1)
C(5)-C(4)-N(1)
C(4)-C(5)-C(6)
C(4)-C(5)-C(10)
C(6)-C(5)-C(10)
C(5)-C(6)-C(7)
C(5)-C(6)-O(6)
C(7)-C(6)-O(6)
C(6)-C(7)-C(8)
C(7)-C(8)-C(9)
C(8)-C(9)-C(10)
C(5)-C(10)-C(9)
Cu-N(1)-C(2)
113.8(3)
106.4(2)
115.0(3)
112.6(2)
119.1(3)
121.2(3)
119.5(3)
118.7(3)
121.2(2)
120.1(2)
120.7(3)
120.0(3)
119.6(4)
121.5(3)
105.1(2)
114.7(2)
112.0(2)
132.9(2)
109.1(1)
N(2)-C(11)
N(2)-C(13)
N(3)-C(11)
N(3)-C(12)
C(12)-C(13)
7 are similar to those for 5 with a number of minor differences
in bond angles (Vide supra).
The asymmetric C(2) and N(1) centers have the S and R
absolute configurations, respectively, as depicted in Figure 2.
The presence of a crystallographic mirror plane means that
symmetry-related molecules have these centers with opposite
chirality, and as for 5, the molecules in the solid state are
diastereoisomers with a trans configuration about C(2)-N(1).
The imidazole is planar and lies at an angle of 10° to the
plane of best fit through the copper coordination sphere. This
is similar to the arrangement found for the coordinated pyrazole
in [Cu(salicylidene-S-alaninato)pyrazole]‚pyrazole.15i Bond dis-
Cu-N(1)-C(4)
C(2)-N(1)-C(4)
Cu-N(3)-C(11)
Cu-N(3)-C(22)
C(11)-N(3)-C(22) 117.7(2) C(11)-N(3)-C(12) 106.9(3)
Cu-N(2)-C(20)
Cu-N(2)-C(21)
125.4(2) C(11)-N(2)-Cu
116.0(2) C(13)-N(2)-Cu
126.0(3)
127.9(2)
C(20)-N(2)-C(21) 118.3(2) C(11)-N(2)-C(13) 105.4(3)
Cu-O(12)-C(1)
Cu-O(6)-C(6)
115.8(2)
119.2(1)
115.5(2)
124.8(2)
111.8(3)
N(2)-C(11)-N(3)
N(3)-C(12)-C(13) 107.3(3)
N(2)-C(13)-C(12) 108.6(3)
tances and angles within the Him moiety are normal.28
A
hydrogen bond between the Him N(3) and O(11) (2.74 Å) helps
to hold molecules in pairs in the a-c plane, with a weak contact
between the amino acid N(1) and the coordinated phenolato
O(6) (3.02 Å) stacking them in b.
Table 6. Electronic Absorption and Conductivity Data for
Complexes
absorption bands (nm)a
Physicochemical Studies. Electronic spectral data for the
complexes as Nujol mulls are presented in Table 6. The mull
transmittance spectra exhibit a charge transfer transition (ct) at
ca. 400 nm, which may be assigned to a ligand to copper(II)
transition. The exceptions to this are 1 and 3, which contain
monodeprotonated ligands and are assumed to have only the
carboxylate deprotonated. The ct transition therefore is assigned
as phenolato to copper, and the absence of this absorption may
tentatively be used as an indication of the coordination mode
for these ligands. Credence is given to this as in 14 where the
monodeprotonated ligand has the carboxylate esterified. The
ct band is seen at 410 nm showing phenolato coordination.
Schiff base complexes of salicylaldehyde with Gly and acetyll-
ysine9 and Ala, Val, Phe, and His25 exhibit this band at higher
energy, ca. 360 nm. The delocalization of charge in the
conjugated Schiff base ligands would be expected to shift the
ct band to higher energy, as is seen. Cu(SalGly) (where SalGly
is salicylaldimine glycinate) and related systems also display a
charge
transfer
molar
complex
d-d
conductivityb
1
2
3
4
5
6
7
8
9
[Cu(HSGly)2]‚0.5H2O
[{Cu(SGly)}2]‚2H2O
[Cu(HSAla)2]‚2H2O
[{Cu(SAla)}2]‚2H2O
[Cu(SAla)phen]‚H2O
[Cu(SAla)py]‚H2O
[Cu(SAla)Him]
sh
386
sh
390sh
400
386
395
sh
400sh
sh
400sh
sh
400sh
410
600
670
600br
685
720
660br
620
690
725
700br
680
0
0
4
2
1
0
1
2
1
1
0
3
0
1
[Cu(HSIle)2]‚2.5H2O
[{Cu(SIle)}2]
10 [Cu(HSLeu)2]‚H2O
11 [{Cu(SLeu)}2]‚H2O
12 [Cu(HSPhe)2]‚3H2O
13 [{Cu(SPhe)}2]
740br
660br
600
14 [Cu(SGlyMe)2]
a Nujol mull transmittance spectra. b In (CH3)2SO, S cm-2 mol-1
.
ct band at ca. 265 nm assigned as a π* r π transition, which
was considered indicative of the salicylaldimine group moiety
in a dianionic ligand. The shift in the ct band to lower energy
at 280-295 nm (DMSO) for this work, where the imine has
been reduced, reinforces this assignment.
Complexes 1 and 3, which have a 1:2 Cu:ligand ratio and a
d-d band at 600 nm, are assigned square planar geometries
(28) (a) Morehouse, S. M.; Polychronopoulou, A.; Williams, G. J. B. Inorg.
Chem. 1980, 19, 3558-3561 and references therein. (b) Glowiak, T.;
Wnek, I. Acta Crystallogr. 1985, C41, 507-510. (c) Antolini, L.;
Marcotrigiano, G.; Menabue, L.; Pellacani, G. C.; Saladini, M.; Sola,
M. Inorg. Chem. 1985, 24, 3621-3626.

6472 Inorganic Chemistry, Vol. 35, No. 22, 1996
Koh et al.
on the basis of a comparison with the square planar 7, which
exhibits a d-d transition at 620 nm. The monodeprotonated
HSGly and HSAla ligands therefore are acting as bidentate
chelators, coordinating through the carboxylato O and amino
N. This is in contrast to amino acid-salicylidene complexes
studied by single-crystal X-ray diffraction where ligands invari-
ably were shown to coordinate as tridentate moieties, incorpo-
rating the phenolato O. The square pyramidal Cu(II) in 5 has
its ligand field transition at longer wavelength, consistent with
the change in geometry.29 In (CH3)2SO solution the d-d
transition does not shift significantly (data not shown), except
for 9 where the band moves from 725 to 660 nm, indicating a
structural change from a square pyramidal 4+1 geometry in
the solid to a solvated 4+2 tetragonal structure in solution. Molar
conductance values in (CH3)2SO indicate that all complexes are
nonelectrolytes, showing that the ligand remains bound, without
further deprotonation, even in such a strongly coordinating
solvent.
positions about the five-membered chelate ring, while the methyl
(C3) and methylene (C4, now in the six-membered chelate ring)
take up equatorial positions. Inversion of either chiral center
gives the diastereomers SS and RR, and minimization of this
structure shows the effect of the steric interactions. For 7 the
angle C2-N1-C4 increased by 2°, pushing C3 and C2 apart,
accompanied by a significant flattening of the chelate rings as
seen from the dihedral angle C1-C2-N1-C4, which increased
from 146° for SR and RS to 158° for SS and RR. The effect of
flattening the chelate rings has been to force the phenyl group
down toward N1(H) by 8° compared to the observed structure.
The net changes result in the SS and RR structures being more
sterically strained and less likely to pack well in the solid state.
In 5 the predominant changes upon inversion of C2 are seen in
the carboxylate, where the torsion Cu-O12-C1-O11 decreases
by 4.6° to 168.2°. The presence of the phen perpendicular to
the SAla ligand appears to have decreased the magnitude of
the effect when compared to 7 and may indicate less of an
energy barrier to N1 inversion in this structure.
The depressed room-temperature magnetic moments for 2
(1.55 µB), 4 (1.31 µB), and 11 (1.57 µB) indicate moderately
strong antiferromagnetic coupling for these complexes. The
structures for these species and those of the other binary
dianionic ligands (9, 11, and 13) are assigned as side-by-side
dimers and assumed to have bridging phenolato moieties.
Dimers bridged through the carboxylate have been considered
by several authors, but in light of the X-ray structures of Cu(II)
with the tyrosine analog30 of the present system, [{Cu(STyr)}2]‚-
3H2O, and structurally related salicylaldehyde acylhydrazones,31
we consider this less probable. The related Schiff base
complexes {Cu(SalVal)}2 and {Cu(SalLeu)}2 were also pro-
posed to be dimers due to their low magnetic moments of 1.35
and 1.56 µB, respectively,2 and Gly analogs of these, [{Cu-
(SalGly)}2]‚nH2O, were found to have moments between 1.33
and 1.86 µB, depending on the state of hydration and crystal-
linity.32 Interestingly, the crystal structure of the reduced-ligand
complex [{Cu(SGly)}2(H2O)]‚H2O has been determined. In this
the Cu(II) centers are bridged by the phenolato O, giving a
planar Cu core with a metal-metal separation of 2.97 Å but a
normal moment of 1.78 µB.33 Our remaining complexes have
µB values that are consistent with magnetically dilute copper-
(II) complexes, as evidenced for monomeric 5 and 7, although
the presence of weakly coupled dimers cannot be ruled out (Vide
supra).
Our results agree with the proposed mechanism for amino
acid racemization. The intermediate formed from protic solvent
addition across the initially formed imine double bond gives a
carbinolamine, where the sterically larger groups in the now
saturated intermediate would occupy equatorial positions on the
puckered chelate ring. Our crystal and energy-minimized
structures agree with this prediction, and the complexes may
serve as models for this imine-reduced intermediate.
Conclusions
Imine-reduced analogs of Schiff base ligands between amino
acids with nonpolar side chains and salicylaldehyde binding
copper(II) have yielded complexes with bi- or tridentate
coordination modes, mono- and dideprotonated ligands, as well
as binary and ternary adducts with Lewis bases. The complexes
appear to the first of their kind containing derivatives of chiral
amino acids with Cu(II) and may serve as models for the
intermediate species in the biological racemization and tran-
samination reactions of amino acids with pyridoxal phosphate.
Adoption of a phenolato-bridged, dimeric structure for dianionic
ligands is consistent with the resulting antiferromagnetic
coupling between the Cu(II) centers observed in the majority
of such complexes. The trans arrangement of the two chiral
centers in the complexed ligand is considered to result from
favorable steric interactions. Studies of amino acids possessing
polar, and potentially coordinating, side chains are in progress
to investigate their coordinating ability with Cu(II), especially
that of histidine, for which the unstable Schiff base has been
studied in detail but with no apparent crystallographic reports.
Molecular Mechanics. Good agreement between the crystal
and minimized structures was obtained by defining parameter
sets for Cu in 5 and 7. Torsions and angles around the metal
were explored to give the best fit without unduly constraining
the geometry. The observed SR and RS arrangements of the
chiral C2 and N1 result in the two H-atoms being in axial
Acknowledgment. Support for this work by the National
University of Singapore (Grants RP930604 and RP950650) is
greatly appreciated, and we thank Dr. Scott Gothe (Tripos Inc.)
for helpful discussion.
(29) Lever, A. B. P. Inorganic Electronic Spectroscopy; Elsevier: Am-
sterdam, 1984.
(30) Kon, O. L.; Ranford, J. D.; Robinson, W.; Svensson, J.; Wu, D. Q.
Manuscript in preparation.
(31) (a) Chan, S. C.; Koh, L. L.; Leung, P.-H.; Ranford, J. D.; Sim, K. Y.
Inorg. Chim. Acta 1995, 236, 101-108. (b) Ainscough, E. W.; Brodie,
A. M.; Dobbs, A.; Ranford, J. D.; Waters, J. M. Submitted for
publication.
Supporting Information Available: Tables detailing the X-ray data
collection and refinement, atomic coordinates, bond distances, bond
angles, anisotropic displacement coefficients, and H-atom coordinates
for 5 and 7 (16 pages). Ordering information is given on any current
masthead page.
(32) Kishita, M.; Nakahara, A.; Kubo, M. Aust. J. Chem. 1964, 17, 810-
813.
(33) Xu, J. X.; Chen, M. Q.; Wang, Z. H.; Zhang, H. L. Acta Chim. Sin.
1989, 434-437.
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