Synthesis and characterization of pseudotetrahedral N2O and N2S zinc(II) complexes of two heteroscorpionate ligands: Models for the binding sites of several zinc metalloproteins

Article abstract of DOI:10.1021/ic990233v

Nine new pseudotetrahedral Zn(II) complexes of the heteroscorpionate ligands (3-tert-butyl-2-hydroxy(or thio)-5-methylphenyl)bis(3,5-dimethylpyrazolyl)methane, L1OH or L2SH, have been prepared and characterized (in most cases crystallographically). Complexes isolated include [(L1O)ZnCl], [(L1O)ZnI], [(L1OH)ZnI₂], [(L1O)ZnCH₃], [(L1O)ZnOAc], [(L1O)ZnSPh], [(L1O)ZnSBz], [(L2S)ZnCH₃], [(L2S)ZnSPh], and [(L2S)₂Zn]. In conjunction with the widely studied tris(pyrazolyl)borates this new series of heteroscorpionates provides a set of isolobal and isoelectronic ligands differing in donor set, i.e. N₃, N₂O, and N₂S. Preliminary reactivity studies with HX species, MeI, or trimethyl phosphate suggest differences between the three sets of ligands.

Full text of DOI:10.1021/ic990233v

Inorg. Chem. 1999, 38, 4593-4600
4593
Synthesis and Characterization of Pseudotetrahedral N2O and N2S Zinc(II) Complexes of
Two Heteroscorpionate Ligands: Models for the Binding Sites of Several Zinc
Metalloproteins
Brian S. Hammes and Carl J. Carrano*
Department of Chemistry, Southwest Texas State University, San Marcos, Texas 78666
ReceiVed February 24, 1999
Nine new pseudotetrahedral Zn(II) complexes of the heteroscorpionate ligands (3-tert-butyl-2-hydroxy(or thio)-
5-methylphenyl)bis(3,5-dimethylpyrazolyl)methane, L1OH or L2SH, have been prepared and characterized (in
most cases crystallographically). Complexes isolated include [(L1O)ZnCl], [(L1O)ZnI], [(L1OH)ZnI2], [(L1O)-
ZnCH3], [(L1O)ZnOAc], [(L1O)ZnSPh], [(L1O)ZnSBz], [(L2S)ZnCH3], [(L2S)ZnSPh], and [(L2S)2Zn]. In
conjunction with the widely studied tris(pyrazolyl)borates this new series of heteroscorpionates provides a set of
isolobal and isoelectronic ligands differing in donor set, i.e. N3, N2O, and N2S. Preliminary reactivity studies
with HX species, MeI, or trimethyl phosphate suggest differences between the three sets of ligands.
Introduction
enzymes, and only recently have efforts by Parkin et. al. been
successful in modifying it systematically to produce ligands with
Zinc-containing proteins constitute the largest group of
metalloproteins. While the zinc in these proteins has very
divergent functions, including both structural and catalytic roles,
the nature of its binding site in these proteins is surprisingly
similar.1 Thus the structure of the Zn site in most proteins can
usually be described as pseudotetrahedral with N, O, or S donor
atoms coming from histidine, tyrosine, aspartic or glutamic
acids, cysteine, and/or water. Given the similarities in the overall
structures, it is particularly important to understand how the
[NxOySz] donor set modulates the reactivity of the pseudotet-
rahedral Zn(II) center.
One way to approach this question is in synthesis, structural
characterization, and reactivity studies of small synthetic
analogues to these Zn metalloenzymes, and extensive efforts
have been undertaken in this regard. The most successful of
these have utilized the tris(pyrazolyl)borates, TpR, as a platform,
since this ligand provides a facial array of three nitrogen donors
from which numerous pseudotetrahedral LZnX complexes have
been prepared in elegant work by the Parkin, Vahrenkamp, and
Kitajima groups.2-10 These complexes are excellent structural
and reactivity models for certain Zn metalloenzymes such as
carbonic anhydrase. However, the Tp group is restricted to
providing N3 donor sets, inappropriate for many of the zinc
mixed N,O,S coordination.11-14 Vahrenkamp and Fenton have
explored other tripodal ligands in an effort to achieve the same
goal.15-18
Nevertheless, thus far, no single family of easily synthesized
complexes with the same coordination geometry, charge, etc.,
and varying only in the donor set, i.e. N3, N2O, and N2S, has
been available for systematic structure and reactivity studies.
Formation of N2S species has been particularly difficult due to
the tendency of the sulfur atoms to bridge and produce
oligomeric structures.19,20 In this report we describe a series of
Zn complexes with two new heteroscorpionate ligands (L1OH
and L2SH) which, along with extensive data already available
for the related tris(pyrazolyl)borates, allows us to begin such
studies.
(1) Lipscomb, W. N.; Straeter, N. Chem. ReV. 1996, 96, 2375.
(2) Alsfasser, R.; Powell, A. K.; Vahrenkamp, H. Angew. Chem., Int. Ed.
Engl. 1990, 29, 898.
(3) Alsfasser, R.; Trofimenko, S.; Looney, A.; Parkin, G.; Vahrenkamp,
H. Inorg. Chem. 1991, 30, 4098.
(4) Looney, A.; Parkin, G.; Alsfesser, R.; Ruf, M.; Vahrenkamp, H. Angew.
Chem., Int. Ed. Engl. 1992, 31, 92.
(5) Ruf, M.; Schell, F. A.; Walz, R.; Vahrenkamp, H. Chem. Ber. 1997,
130, 101.
(6) Weiss, K.; Rombach, M.; Ruf, M.; Vahrenkamp, H. Eur. J. Inorg.
Chem. 1998, 263.
(7) Ruf, M.; Vahrenkamp, H. Inorg. Chem. 1996, 35, 6571.
(8) Kitajima, N.; Hikichi, S.; Tanaka, M.; Moro-oka, Y. J. Am. Chem.
Soc. 1993, 113, 3490.
(11) Ghosh, P.; Parkin, G. J. Chem. Soc., Chem. Commun. 1998, 413.
(12) Dowling, C.; Parkin, G. Polyhedron 1996, 15, 2463.
(13) Kimblin, C.; Hascall, T.; Parkin, G. Inorg. Chem. 1997, 36, 5680.
(14) Schebler, P. J.; Riordan, C. G.; Guzei, I. A.; Rheingold, A. L. Inorg.
Chem. 1998, 37, 4754.
(15) Abufarag, A.; Vahrenkamp, H. Inorg. Chem. 1995, 34, 2207.
(16) Troesch, A.; Vahrenkamp, H. Eur. J. Inorg. Chem. 1998, 827.
(17) Burth, R.; Stange, A.; Schaefer, M.; Vahrenkamp, H. Eur. J. Inorg.
Chem. 1998, 1759.
(18) Rodriguez de Barbarin, C. O.; Bailey, N. A.; Fenton, D. E.; He, Q. J.
Chem. Soc., Dalton Trans. 1997, 161.
(9) Looney, A.; Han, R.; McNeill, K.; Parkin, G. J. Am. Chem. Soc. 1993,
113, 4690.
(10) Ruf, M.; Weis, K.; Brasack, I.; Vahrenkamp, H. Inorg. Chim. Acta
1996, 250, 271.
(19) Dance, I. G. Polyhedron 1986, 5, 1037.
(20) Prince, R. H. In ComprehensiVe Coordination Chemistry; Wilkinson,
G., Gillard, R. D., McCleverty, J. A., Eds.; Pergamon: London, 1988;
Vol. 5, p 925.
10.1021/ic990233v CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/15/1999

4594 Inorganic Chemistry, Vol. 38, No. 20, 1999
Hammes and Carrano
(57.61); H, 6.72 (6.61); N, 11.13 (10.77). FTIR (KBr, cm-1): νCO(OAc-)
) 1601, 1393. H NMR (CD2Cl2): δ 7.00 (d, 1 H, J ) 2 Hz, ArH),
Experimental Section
1
All syntheses were carried out in air and the reagents and solvents
purchased from commercial sources and used as received unless
otherwise noted. Toluene and dichloromethane were distilled under
argon over Na/benzophenone and CaH2, respectively. The syntheses
of ligands (3-tert-butyl-2-hydroxy-5-methylphenyl)bis(3,5-dimeth-
ylpyrazolyl)methane (L1OH) and of (3-tert-butyl-5-methyl-2-thiophe-
nyl)bis(3,5-dimethylpyrazolyl)methane (L2SH) followed the reported
procedures.21,22
[(L1O)ZnCl] (1). A solution of L1OH (0.33 g, 0.89 mmol) in 25
mL of CH3CN was treated with solid NaOMe (0.048 g, 0.89 mmol)
and stirred for 0.5 h. An CH3CN solution of ZnCl2‚6H2O (0.22 g, 0.89
mmol) was added to the reaction mixture. The resulting solution was
stirred for 2 h, concentrated under reduced pressure, and filtered to
give a white solid. The white solid was treated with dichloromethane
and filtered to remove a small amount of insoluble material (NaCl).
The filtrate was concentrated under reduced pressure and crystallized
by layering the solution with isopropyl ether (0.27 g, 65%). Anal. Calcd
(found) for [(L1O)ZnCl], C22H29ClN4OZn: C, 56.66 (56.33); H, 6.28
(6.32); N, 12.01 (11.86). 1H NMR (CDCl3): δ 7.07 (d, 1 H, J ) 2 Hz,
ArH), 6.90 (s, 1H, -CH-), 6.69 (d, 1 H, J ) 2 Hz, ArH), 5.94 (s, 1
H, PzH), 2.47 (s, 6 H, Pz-CH3), 2.42 (s, 6 H, Pz-CH3), 2.20 (s, 3 H,
Ar-CH3), 1.39 (s, 9 H, -C(CH3)3). 13C NMR (CDCl3): δ 150.53,
140.59, 130.29, 129.06, 120.61, 119.69, 106.71, 73.49, 35.49, 29.43,
20.42, 13.08, 11.59.
6.91 (s, 1H, -CH-), 6.71 (d, 1 H, J ) 2 Hz, ArH), 5.97 (s, 1 H,
PzH), 2.46 (s, 6 H, Pz-CH3), 2.31 (s, 6 H, Pz-CH3), 2.17 (s, 3 H,
Ar-CH3), 2.14 (s, 3 H, OC(O)CH3), 1.35 (s, 9 H, -C(CH3)3). 13C NMR
(CD2Cl2): δ 150.31, 142.02, 141.01, 129.94, 129.00, 120.42, 119.20,
106.59, 73.53, 65.70, 35.34, 29.29, 21.56, 20.18, 15.22, 12.69, 11.57.
[(L1O)ZnSPh] (6). A solution of 4 (0.41 g, 0.91 mmol) in 20 mL
of CH2Cl2 was treated with a CH2Cl2 solution of thiophenol (0.10 g,
0.91 mmol). The resulting solution was stirred for 1 h, dried under
reduced pressure, and crystallized by layering an CH2Cl2 solution of
the complex with isopropyl ether to yield 0.18 g (34%). Anal. Calcd
(found) for [(L1O)ZnSPh], C28H34N4OSZn: C, 62.26 (62.11); H, 6.36
1
(6.23); 10.37 (10.34). H NMR (CDCl3): δ 7.69 (d, 2 H, J ) 7 Hz,
SArH), 7.09 (d, 1 H, J ) 2 Hz, ArH), 7.08 (t, 2 H, J ) 7 Hz, SArH),
6.97 (t, 1 H, J ) 7 Hz, SArH), 6.92 (s, 1 H, -CH-), 6.71 (d, 1 H, J
) 2 Hz, ArH), 5.90 (s, 1 H, PzH), 2.45 (s, 6 H, Pz-CH3), 2.24 (s, 6
H, Pz-CH3), 2.21 (s, 3 H, Ar-CH3), 1.41 (s, 9 H, -C(CH3)3). 13C
NMR (CDCl3): δ 150.44, 142.64, 140.63, 140.40, 132.54, 130.24,
129.11, 128.16, 122.59, 120.38, 119.92, 106.67, 73.45, 35.43, 29.40,
20.41, 12.84, 11.61.
[(L1O)ZnSBz] (7). A solution of 4 (0.45 g, 1.1 mmol) in 20 mL of
CH2Cl2 was treated with a CH2Cl2 solution of benzyl mercaptan (0.13
g, 1.1 mmol). The resulting solution was stirred for 15 h and dried
under reduced pressure to give [(L1O)ZnSBz] (0.36 g, 60%) as a white
1
solid. H NMR (CDCl3): δ 7.50 (d, 2 H, J ) 7 Hz, SCH2ArH), 7.23
[(L1OH)ZnI2] (2). A solution of L1OH (0.22 g, 0.60 mmol) in 25
mL of CH3CN was treated with a CH3CN solution of ZnI2 (0.19 g,
0.60 mmol). The resulting reaction mixture was stirred for 2 h,
concentrated under reduced pressure, and filtered to give a white solid.
Layering a CH2Cl2 solution of [(L1OH)ZnI2] with isopropyl ether
crystallized the complex (0.29 g, 81%). Anal. Calcd (found) for
[(L1OH)ZnI2]‚CH2Cl2, C23H32Cl2I2N4OZn: C, 35.85 (36.20); H, 4.19
(t, 2 H, J ) 7 Hz, SCH2ArH), 7.12 (t, 1 H, J ) 7 Hz, SCH2ArH), 7.10
(d, 1 H, J ) 2 Hz, ArH), 6.89 (s, 1 H, -CH-), 6.73 (d, 1 H, J ) 2 Hz,
ArH), 5.87 (s, 1 H, PzH), 4.08 (s, 2 H, SCH2Ar), 2.45 (s, 6 H, Pz-
CH3), 2.22 (s, 6 H, Pz-CH3), 2.22 (s, 3 H, Ar-CH3), 1.45 (s, 9 H,
-C(CH3)3). 13C NMR (CDCl3): δ 163.20, 150.34, 145.70, 142.32,
140.18, 140.40, 130.12, 129.09, 128.33, 128.13, 125.50, 120.08, 119.97,
107.06, 106.46, 73.43, 35.54, 29.64, 29.57, 20.52, 13.03, 11.70.
[(L2S)ZnCH3] (8). A solution of L2SH (0.78 g, 2.0 mmol) in 50
mL of toluene was treated with a toluene solution of Zn(CH3)2 (0.19
g, 2.0 mmol) under argon. The resulting solution was stirred for 1 h
and filtered to yield 0.39 g (43%) of [(L2S)ZnCH3]. Anal. Calcd (found)
for [(L2S)ZnCH3]‚0.3C7H8, C25.1H34.4N4SZn: C, 61.56 (61.66); H, 7.09
1
(4.08); N, 7.26 (7.25). FTIR (KBr, cm-1): νOH(Ar-OH) ) 3588. H
NMR (CDCl3): δ 7.73 (s, 1 H, -CH-), 7.17 (d, 1 H, J ) 2 Hz, ArH),
7.03 (d, 1 H, J ) 2 Hz, ArH), 6.04 (s, 1 H, PzH), 5.15 (s, 1 H, OH),
2.60 (s, 6 H, Pz-CH3), 2.51 (s, 6 H, Pz-CH3), 2.29 (s, 3 H, Ar-
CH3), 1.39 (s, 9 H, -C(CH3)3). 13C NMR (CDCl3): δ 154.95, 147.93,
143.89, 133.75, 131.19, 129.54, 127.05, 122.13, 108.22, 64.41, 33.55,
30.55, 21.13, 15.18, 11.66.
1
(6.89); N, 11.44 (11.24). H NMR (CD2Cl2): δ 7.17 (d, 1 H, J ) 2
Hz, ArH), 7.14 (s, 1H, -CH-), 6.80 (d, 1 H, J ) 2 Hz, ArH), 6.02 (s,
1 H, PzH), 2.38 (s, 6 H, Pz-CH3), 2.29 (s, 6 H, Pz-CH3), 2.22 (s, 3
H, Ar-CH3), 1.58 (s, 9 H, -C(CH3)3), -0.62 (s, 3 H, Zn-CH3). 13C
NMR (CD2Cl2): δ 153.12, 150.84, 142.24, 135.81, 130.59, 130.46,
129.73, 129.43, 107.53, 75.60, 38.15, 30.49, 20.99, 13.54, 12.15,
-14.71.
[(L1O)ZnI] (3). A solution of L1OH (0.48 g, 1.3 mmol) in 25 mL
of CH3CN was treated with solid NaOMe (0.054 g, 1.3 mmol) and
stirred for 0.5 h. A CH3CN solution of ZnI2 (0.41 g, 1.3 mmol) was
added to the reaction mixture. The resulting solution was stirred for 2
h, concentrated under reduced pressure, and crystallized by layering
the CH2Cl2 solution with isopropyl ether (0.36 g, 50%). Anal. Calcd
(found) for [(L1O)ZnI]‚0.35CH2Cl2, C22.35H29.7Cl0.7IN4OZn: C, 45.69
[(L2S)ZnSPh] (9). A solution of 8 (0.11 g, 0.23 mmol) in 20 mL
of CH2Cl2 was treated with a CH2Cl2 solution of thiophenol (0.026 g,
0.23 mmol). The resulting solution was stirred for 1 h, dried under
reduced pressure, and crystallized by layering a CH2Cl2 solution of
[(L2S)ZnSPh] with isopropyl ether to yield 0.063 g (49%) of the
complex. Anal. Calcd (found) for [(L2S)ZnSPh]‚0.4CH2Cl2, C28.4H34.8N4-
1
(45.58); H, 5.11 (4.92); N, 9.54 (9.34). H NMR (CDCl3): δ 7.07 (d,
1 H, J ) 2 Hz, ArH), 6.91 (s, 1H, -CH-), 6.69 (d, 1 H, J ) 2 Hz,
ArH), 5.93 (s, 1 H, PzH), 2.48 (s, 6 H, Pz-CH3), 2.47 (s, 6 H, Pz-
CH3), 2.20 (s, 3 H, Ar-CH3), 1.39 (s, 9 H, -C(CH3)3). 13C (CDCl3):
δ 163.33, 150.80, 142.71, 140.31, 130.17, 128.82, 120.47, 119.65,
107.02, 73.45, 35.51, 29.47, 20.53, 13.97, 11.70.
1
Cl 0.4S2Zn: C, 57.80 (57.21); H, 5.96 (5.85); 9.49 (9.34). H NMR
(CDCl3): δ 7.52 (d,2 H, J ) 7 Hz, SArH), 7.23 (d, 1 H, J ) 2 Hz,
ArH), 7.18 (s, 1 H, -CH-), 7.04 (t, 2 H, J ) 7 Hz, SArH), 6.93 (t, 1
H, J ) 7 Hz, SArH), 6.77 (d, 1 H, J ) 2 Hz, ArH), 5.98 (s, 2 H, PzH),
2.43 (s, 6 H, Pz-CH3), 2.26 (s, 6 H, Pz-CH3), 2.25 (s, 3 H, Ar-
CH3), 1.62 (s, 9 H, -C(CH3)3). 13C NMR (CDCl3): δ 153.77, 151.65,
141.91, 141.18, 135.12, 132.35, 130.79, 129.65, 128.04, 122.44, 107.68,
74.99, 37.84, 30.38, 20.88, 13.07, 11.84.
[(L1O)ZnCH3] (4). A solution of L1OH (2.1 g, 5.7 mmol) in 100
mL of toluene was treated with a toluene solution of Zn(CH3)2 (0.54
g, 5.7 mmol) under argon. The resulting solution was stirred for 1 h
and filtered to yield 2.31 g (91%) of [(L1O)ZnCH3]. Anal. Calcd (found)
for [(L1O)ZnCH3]‚0.25H2O, C23H32.5N4O1.25Zn: C, 61.32 (61.38); H,
1
7.29 (7.27); 12.44 (12.77). H NMR (CDCl3): δ 7.02 (d, 1 H, J ) 2
Hz, ArH), 6.82 (s, 1 H, -CH-), 6.68 (d, 1 H, J ) 2 Hz, ArH), 5.85
(s, 1 H, PzH), 2.43 (s, 6 H, Pz-CH3), 2.27 (s, 6 H, Pz-CH3), 2.18 (s,
3 H, Ar-CH3), 1.38 (s, 9 H, -C(CH3)3), -0.59 (s, 3 H, Zn-CH3).
13C NMR (CDCl3): δ 164.12, 149.29, 142.13, 139.56, 129.66, 128.78,
120.20, 118.62, 106.09, 73.30, 35.33, 29.29, 20.43, 13.06, 11.54,
-17.03.
[(L1O)ZnOAc] (5). A solution of 4 (0.40 g, 0.90 mmol) in 30 mL
of CH2Cl2 was treated 1 equiv of HOAc (0.054 g, 0.90 mmol) under
argon. The resulting solution was stirred for 1 h and concentrated under
reduced pressure. The complex was crystallized by layering a concen-
trated CH2Cl2 solution with diethyl ether (0.39 g, 85%). Anal. Calcd
(found) for [(L1O)ZnOAc]‚0.75H2O, C24H33.5N4O3.75Zn: C, 57.25
[(L2S)2Zn] (10). The zinc complex 8 (0.10 g, 0.21 mmol) was
dissolved in 20 mL of undried CH2Cl2. The resulting solution was stirred
for 1 h, concentrated under reduced pressure, and crystallized by
layering the CH2Cl2 solution with isopropyl ether to yield 0.042 g
(25%). Anal. Calcd (found) for [(L2S)2Zn], C44H58N8S2Zn: C, 63.78
(63.68); H, 7.07 (6.88); 13.52 (13.51). 1H NMR (CDCl3): δ 10.28 (s,
1 H, -CH), 7.67 (d, 1 H, ArH), 7.13 (d, 1 H, ArH), 5.93 (s, 1 H,
PzH), 5.61 (s, 1 H, PzH), 2.31 (s, 3 H, Pz-CH3), 2.27 (s, 3 H, Pz-
CH3), 2.22 (s, 3 H, Ar-CH3), 1.79 (s, 3 H, Pz-CH3), 1.49 (s, 9 H,
-C(CH3)3), 0.68 (s, 3 H, Pz-CH3). 13C NMR (CDCl3): δ 150.64,
148.50, 147.82, 142.47, 140.80, 140.11, 136.78, 131.08, 129.24, 128.59,
108.17, 106.96, 72.43, 37.41, 30.16, 21.66, 14.08, 11.09, 10.84, 10.47.

Pseudotetrahedral N2O and N2S Zn(II) Complexes
Inorganic Chemistry, Vol. 38, No. 20, 1999 4595
Table 1. Summary of Crystallographic Data and Parameters for [(L1O)ZnCl] (1), [(L1OH)ZnI2]‚CH2Cl2 (2), [(L1O)ZnCH3] (4),
[(L1O)ZnOAc]‚(CH3CH2)2O (5), [(L1O)ZnSPh]‚0.5H2O (6), [(L2S)ZnSPh]‚0.5CH2Cl2 (8), and [(L2S)2Zn] (9)
1
2
4
5
6
8
9
molecular formula C22H29ClN4OZn C23H32Cl2I2N4OZn C23H32N4OZn
C28H42N4O4Zn C28H35N4O1.5SZn C28.5H35ClN4S2Zn C44H58N8S2Zn
fw
466.31
198(2)
monoclinic
P21/m
809.31
198(2)
Monoclinic
P21/c
445.99
198(2)
monoclinic
P21/m
564.14
198(2)
triclinic
P1h
549.03
198(2)
triclinic
P1h
598.27
198(2)
triclinic
P1h
828.47
293(2)
orthorhombic
P212121
temp (K)
cryst system
space group
cell constants
a (Å)
9.412(3)
13.222(4)
18.928(6)
90
91.34(3)
90
11.362(2)
14.205(4)
17.831(3)
90
91.451(11)
90
9.5569(10)
13.139(3)
18.739(2)
90
91.202(8)
90
9.2239(11)
11.6457(12)
13.485(2)
69.304(9)
87.755(9)
85.424(9)
2
14.5238(8)
15.217(2)
15.452(2)
76.698(9)
65.290(9)
66.110(6)
2
13.148(2)
15.276(2)
15.824(4)
73.609(11)
85.442(12)
71.044(9)
2
10.996(2)
14.959(2)
26.801(3)
90
90
90
b (Å)
c (Å)
R (deg)
â (deg)
γ (deg)
Z
4
6
4
4
V (Å3)
2354.9(14)
1.175
2877.0(10)
3.208
2352.6(6)
1.291
1350.6(3)
1.137
2829.1(5)
0.970
2883.4(9)
1.111
4408.5(13)
0.692
abs coeff, µcalc
(mm-1
)
δ
calc (g/cm3)
F(000)
1.315
976
1.779
1504
1.397
1016
1.347
558
1.289
1156
1.335
1212
1.248
1760
cryst dimens
(mm)
0.2 × 0.3 ×
0.7 × 0.7 ×
0.7 × 0.7 ×
0.7 × 0.7 ×
0.4 × 0.4 ×
0.9 × 0.4 ×
0.6 × 0.4 ×
0.1
0.7
0.2
0.4
0.2
0.15
0.4
radiation (λ (Å))
Mo KR
(0.710 73)
0 f 8,
0 f 14,
-20 f 20
1.88-22.50
3181
Mo KR
(0.710 73)
0 f 12,
0 f 14,
-19 f 19
1.83-22.50
4063
Mo KR
(0.710 73)
0 f 10,
-12 f 0,
-20 f 20
1.89-22.50
3237
Mo KR
(0.710 73)
0 f 8,
-11 f 11,
-14 f 14
1.87-22.50
3498
Mo KR
(0.710 73)
0 f 12,
-14 f 16,
-15 f 16
1.78-22.50
7159
Mo KR
Mo KR
(0.710 73)
-11 f 0,
-15 f 0,
-28 f 0
2.00-22.49
2851
(0.710 73)
-14 f 0,
-14 f 14,
-17 f 16
2.03-22.50
7464
h,k,l ranges
collcd
θ range (deg)
no. of reflcns
collcd
no. of unique
reflcns
2957
3523
3040
3240
6812
7101
2819
no. of params
data/param ratio
refinement
method
301
9.81
full-matrix
least squares
on F2
0.0701
0.1439
1.041
298
11.82
full-matrix
least squares
of F2
0.0436
0.1131
1.130
301
10.06
full-matrix
least squares
of F2
0.0542
0.1459
1.075
332
9.75
full-matrix
least squares
of F2
0.0523
0.1350
0.981
646
10.52
full-matrix
least squares
of F2
0.0676
0.1848
1.064
677
10.49
full-matrix
least squares
of F2
0.0433
0.1083
0.973
497
5.67
full-matrix
least squares
of F2
0.0419
0.1053
1.041
R(F)a
Rw(F2)b
GOFwc
largest diff
peak and
hole (e/Å3)
0.467, -0.398
1.006, -1.493
0.746, -1.154
0.465, -0.710
1.299, -1.368
0.899, -0.579
0.409, -0.650
a R ) [∑|∆F|/∑|Fo|]. b Rw ) [∑w(∆F)2/∑wFo ]. c Goodness of fit on F2.
2
Physical Methods. Elemental analyses were performed on all
compounds by Desert Analytics, Inc., Tucson, AZ, or Quantitative
Technologies, Inc., Whitehouse, NJ. All samples were dried in vacuo
prior to analysis. The presence of solvates was corroborated by FTIR,
of both crystallographically independent molecules are available in the
Supporting Information. The asymmetric unit of [(L2S)ZnSPh]‚0.5CH2-
Cl2 contains half of a molecule of CH2Cl2 while [(L1OH)ZnI2]‚CH2-
Cl2 contains a full molecule of this solvent. The asymmetric unit of
[(L1O)ZnSPh]‚0.5H2O contains half of a molecule of H2O, and that of
[(L1O)ZnOAc]‚(CH3CH2)2O contains a highly disordered lattice diethyl
ether. All non-hydrogen atoms were refined with anisotropic displace-
ment coefficients and treated as idealized contributions using a riding
model except where noted. All software and sources of the scattering
factors are contained in the SHELXTL (5.0) program library (G.
Sheldrick, Siemens XRD, Madison WI).
1
1H NMR, or X-ray crystallography. H and 13C NMR spectra were
collected on a Varian UNITY INOVA 400 MHz NMR spectrometer.
Chemical shifts are reported in ppm relative to an internal standard of
TMS. The 13C quaternary carbon peaks that are not observed are a
result of either poor solubility and/or overlapping signals. IR spectra
were recorded from KBr disks on a Perkin-Elmer 1600 Series FTIR
spectrometer and are reported in wavenumbers.
Crystallographic Structure Determination. Crystal, data collection,
and refinement parameters for [(L1O)ZnCl] (1), [(L1OH)ZnI2] (2),
[(L1O)ZnCH3] (4), [(L1O)ZnOAc] (5), [(L1O)ZnSPh] (6), [(L2S)-
ZnSPh] (9), and [(L2S)2Zn] (10) are given in Table 1. Crystals of all
complexes were sealed in thin-walled quartz capillaries, and data
collection was initiated at 198 K except for 10, the data for which
were obtained at room temperature. The systematic absences in the
diffraction data are consistent with the space groups P1h for [(L1O)-
ZnOAc]‚(CH3CH2)2O, [(L1O)ZnSPh]‚0.5H2O, and [(L2S)ZnSPh]‚
0.5CH2Cl2, P21/m for [(L1O)ZnCl] and [(L1O)ZnCH3], P21/c for
[(L1OH)ZnI2]‚CH2Cl2, and P212121 for [(L2S)2Zn]. The structures were
solved using either direct methods or Patterson techniques, completed
by subsequent difference Fourier syntheses, and refined by full-matrix
least-squares procedures on F2. The metal complexes [(L1O)ZnCl] (1),
[(L1O)ZnCH3] (4), [(L1O)ZnSPh] (6), and [(L2S)ZnSPh] (9) all
crystallized with two crystallographically independent, but virtually
identical, molecules per unit cell. The metrical parameters quoted in
the text refer to only one of the molecules, but structural parameters
Results
Solid-State Structures of the Complexes. The single-crystal
X-ray diffraction studies on [(L1O)ZnCl], [(L1OH)ZnI2], [(L1O)-
ZnCH3], [(L1O)ZnOAc], [(L1O)ZnSPh], and [(L2S)ZnSPh]
confirm that (L1O)- or (L2S)-, formed by deprotonation of the
phenol oxygen or thiophenol sulfur in L1OH or L2SH,
respectively, binds to the zinc in a tridentate fashion. Selected
bond distances and angles for these complexes are shown in
Tables 2 and 3, and Figures 1-4 contain the thermal ellipsoid
diagrams. The molecular structures of [(L1OH)ZnI2] (2) and
[(L2S)2Zn] (10), however, show different coordination modes
of the ligands (Figures 1B and 5), and selected bond lengths
and angles for these species are found in Tables 2 and 4,
respectively.

4596 Inorganic Chemistry, Vol. 38, No. 20, 1999
Hammes and Carrano
Table 2. Selected Bond Distances (Å) and Angles (deg) for [(L1O)ZnCl] (1), [(L1OH)ZnI2] (2), [(L1O)ZnCH3] (4), and [(L1O)ZnOAc] (5)a
1
2
4
5
Zn(1)-N(2)
Zn(1)-N(2)#1
Zn(1)-N(4)
Zn(1)-O(1)
Zn(1)-O(2)
Zn(1)-O(3)
Zn(1)-Cl(1)
Zn(1)-I(1)
2.030(8)
2.030(8)
2.042(6)
2.077(4)
2.077(4)
2.033(4)
2.047(6)
2.066(4)
1.909(3)
1.945(4)
2.476(5)
1.901(10)
1.923(5)
2.162(5)
2.5383(10)
2.5548(10)
Zn(1)-I(2)
Zn(1)-C(33)
1.952(7)
87.0(2)
N(2)-Zn(1)-N(2)#1
N(2)-Zn(1)-N(4)
N(2)-Zn(1)-O(1)
N(2)#1-Zn(1)-O(1)
N(4)-Zn(1)-O(1)
87.7(5)
92.7
89.33(14)
99.73(13)
100.3(3)
100.3(3)
95.6(2)
95.6(2)
97.10(13)
a Numbers in parentheses are estimated standard deviations.
Table 3. Selected Bond Distances (Å) and Angles (deg) for
[(L1O)ZnS-Ph] (6) and [(L2S)ZnS-Ph] (8)a
6
8
Zn(1)-N(2)
Zn(1)-N(4)
Zn(1)-O(1)
Zn(1)-S(1)
Zn(1)-S(2)
2.065(6)
2.040(2)
1.921(5)
2.221(2)
2.030(4)
2.052(4)
2.246(1)
2.273(1)
N(2)-Zn(1)-N(4)
N(2)-Zn(1)-O(1)
N(4)-Zn(1)-O(1)
S(1)-Zn(1)-O(1)
S(1)-Zn(1)-N(2)
S(1)-Zn(1)-N(4)
S(1)-Zn(1)-S(2)
S(2)-Zn(1)-N(2)
S(2)-Zn(1)-N(4)
89.6(2)
93.8(2)
100.2(2)
127.7(2)
121.8(2)
115.5(2)
91.13(14)
118.91(10)
117.67(10)
122.16(5)
102.44(10)
98.64(10)
a Numbers in parentheses are estimated standard deviations.
Complexes Containing (L1O)-. The single-crystal X-ray
diffraction study on [(L1OH)ZnI2] (Figure 1B) confirms the
tetrahedral coordination geometry around the zinc ion with two
pyrazolyl nitrogen donors of L1OH and two I- ions coordinated
to the zinc ion. The N(2)-Zn(1)-N(4) bond angle in [(L1OH)-
ZnI2] is 92.7(2)°, while the iodide ions occupy the two remaining
coordination sites cis to the pyrazole rings with the average Npz-
Zn-I bond angle of 111.7(1)°. The phenol oxygen is protonated
and not coordinated to the Zn(II) but is rotated away from the
metal and oriented in such a way that oxygen O(1) is pointed
toward an iodide ion of an adjacent molecule with an O(1)H‚
‚‚I distance of 3.68-3.78 Å.23
[(L1O)ZnCl] (Figure 1A), [(L1O)ZnCH3] (Figure 2), and
[(L1O)ZnSPh] (Figure 4A) all display a pseudotetrahedral
geometry around the metal where the two pyrazolyl nitrogens
and one phenolate oxygen donor from (L1O)- constitute the
trigonal face of the tetrahedron. The average Npz-Zn-Oph angle
for these complexes are similar, ranging from 95.6(2)° for
[(L1O)ZnCH3] to 100.3(3)° for [(L1O)ZnCl]. The Npz-Zn-
Npz bond angle ranges from 87.0(2)° for [(L1O)ZnCH3] to 89.6-
(2)° for [(L1O)ZnSPh]. Both the Npz-Zn-Npz and average
Npz-Zn-Oph bond angles in the complex deviate from the
109.5° angle expected for idealized tetrahedral geometry due
to the relatively small bite angle of the ligand. In all cases the
Figure 1. ORTEP diagram with 30% thermal ellipsoids for (a) [(L1O)-
ZnCl] and (b) [(L1OH)ZnI2] showing atomic labeling for the coordina-
tion sphere only.
seven-membered chelate ring, which contains the phenolate
oxygen, supports the larger internal angle. The Cl- ligand in
[(L1O)ZnCl] is positioned perpendicular to the trigonal plane
formed by the two pyrazolyl nitrogens and the phenolate oxygen
of (L1O)- which results in an average Zn(1)-Cl(1) bond
distance of 2.162(5) Å and average Npz-Zn(1)-Cl(1) and
O(1)-Zn(1)-Cl(1) bond angles of 123.2(3) and 116.3(3)°,
respectively. In [(L1O)ZnCH3], the Zn(1)-C(33) bond distance
of 1.952(7) Å is not unusual and is similar to those reported
for other zinc complexes.24 In [(L1O)ZnSPh] the thiophenol (S-
Ph)- occupies the fourth coordination site on the zinc with a
Zn(1)-S(1) bond distance of 2.224(1) Å and average Npz-
Zn(1)-S(1) and Oph-Zn(1)-S(1) bond angles of 118.6(1) and
127.2(2)°, respectively.
(21) Hammes, B. S.; Carrano, C. J. Inorg. Chem. 1999, 38, 3562.
(22) Higgs, T.; Carrano, C. J. Manuscript in preparation.
(23) Desiraju, G. D. Crystal Engineering: Design of Organic Solids;
Elsevier: New York, 1989.
(24) Looney, A.; Han, R.; Gorrell, I. B.; Cornebise, M.; Yoon, K.; Parkin,
G.; Rheingold, A. L. Organometallics 1995, 14, 274.

Pseudotetrahedral N2O and N2S Zn(II) Complexes
Inorganic Chemistry, Vol. 38, No. 20, 1999 4597
Figure 2. ORTEP diagram with 30% thermal ellipsoids for [(L1O)-
ZnCH3] showing atomic labeling for the coordination sphere only.
Figure 4. ORTEP diagram with 30% thermal ellipsoids for (a) [(L1O)-
ZnSPh] and (b) [(L2S)ZnSPh] showing atomic labeling for the
coordination sphere only.
Figure 3. ORTEP diagram with 30% thermal ellipsoids for [(L1O)-
ZnOAc] showing atomic labeling for the coordination sphere only.
The molecular structure of [(L1O)ZnOAc] (Figure 3) shows
a distorted geometry about the Zn(II) ion with the two pyrazole
nitrogen and the phenolate oxygen from the tridentate ligand
(L1O)- coordinated facially to the metal ion. The N(2)-Zn-
(1)-N(4) and average Npz-Ni(1)-O(1) bond angle for [(L1O)-
ZnOAc] are 89.33(14) and 98.41(10)°, respectively. The acetate
is bound neither in a unidentate nor symmetrical bidentate
fashion, adopting instead an intermediate coordination mode
with Zn(1)-Oacetate bond lengths of 1.945(4) and 2.475(5) Å
and a Zn(1)-O(2)-C(24) bond angle of 105.1(4)°.25 The
analogous binding of nitrate to the phenyl-substituted tris-
(pyrazolyl)borate shows virtually identical metrical parameters.
Both nitrate and acetate bind to the more sterically congested
tert-butyl-substituted derivative in a unidentate fashion with Zn-
Figure 5. ORTEP diagram with 30% thermal ellipsoids for [(L2S)2Zn]
showing atomic labeling for the coordination sphere only.
O
acetate bonds of 1.859 and 2.95 Å and a near 109° M-Oacetate
-
C
acetate angle reported for the latter.24 These observations suggest
that steric interactions play a major role. However electronic
factors are also important since the Cu analogue of [(L1O)-
ZnOAc] shows symmetrical bidentate acetate coordination with
both Cu-O bonds near 2.005(5) Å and a M-O-C angle of
89.2(8)°.26 Parkin has shown that the mode of nitrate binding
to the metal in the tert-butyl-substituted tris(pyrazolyl)borate
complexes varies as a function of metal from strictly unidentate
(Zn) to asymmetric (Co) to symmetrical bidentate (Ni and Cu).25
This has led to the hypothesis that the binding mode of
potentially bidentate ligands such as acetate and nitrate to the
Zn reflects the order of reactivity of the purported bicarbonate
intermediate in carbonic anhydrase catalyzed hydration of CO2,
i.e. Zn > Co . Cu, Ni.9 Both mono- and bidentate binding of
aspartate and glutamate residues to Zn in the active site of many
Zn metalloproteases is known.1
(25) Parkin has discussed the use of the M-O-X angle as a rapid indicator
of the denticity of the acetate in such complexes with unidentate
binding displaying a 109° M-O-X angle and with a symmetrical
bidentate acetate showing an angle of 90°; see: Han, R.; Parkin, G.
J. Am. Chem. Soc. 1991, 113, 9707.
(26) Hammes, B. S.; Carrano, C. J. Unpublished observations.

4598 Inorganic Chemistry, Vol. 38, No. 20, 1999
Hammes and Carrano
Table 4. Selected Bond Distances (Å) and Angles (deg) for
[(L2S)2Zn] (9)a
dried. The final product of this reaction however was not the
expected hydroxo complex but rather a tetrahedral N2S2 species
[(L2S)2Zn] produced according to the following overall reaction:
Zn(1)-N(2)
Zn(1)-N(6)
2.083(7)
2.085(6)
Zn(1)-S(1)
Zn(1)-S(2)
2.286(2)
2.295(2)
2[(L2S)ZnCH3] + 2H2O f 2CH4v + Zn(OH)2V +
N(2)-Zn(1)-N(6)
S(1)-Zn(1)-N(2)
S(1)-Zn(1)-N(6)
103.8(3)
112.6(2)
107.1(2)
S(1)-Zn(1)-S(2)
S(2)-Zn(1)-N(2)
S(2)-Zn(1)-N(6)
112.28(9)
108.5(2)
112.4(2)
[(L2S)2Zn] (1)
Presumably the first step in the reaction sequence is protonation
of the bound CH3 and its loss as methane leaving [(L2S)ZnOH],
indicating a much greater overall reactivity of [(L2S)ZnCH3]
vs [(L1O)ZnCH3]. However, [(L2S)ZnOH] appears to be
unstable and quickly rearranges to Zn(OH)2 and [(L2S)2Zn]
driven both by the insolubility of the zinc hydroxide and the
apparently enormous preference of Zn(II) to adopt a tetrahedral
N2S2 geometry as recently pointed out by Vahrenkamp.27 It is
perhaps then not surprising that the N2S2 motif should have been
used by nature as a very stable structural unit in the zinc finger
proteins.
a Numbers in parentheses are estimated standard deviations.
Complexes Containing (L2S)-. The complex [(L2S)ZnSPh],
Figure 4B, shows a pseudotetrahedral coordination geometry
about the Zn(II) ion where the two pyrazole nitrogens and one
thiophenolate sulfur, from (L2S)-, coordinate facially. This
results in N(2)-Zn(1)-N(4) and average Npz-Zn(1)-S(2) bond
angles of 91.13(14) and 118.29(7)°, respectively, and Zn(1)-
S(2) and average Zn(1)-Npz bond distances of 2.246(1) and
2.041(3) Å. The exogenous “axial” thiolate S(1) is positioned
nearly perpendicular to the trigonal plane formed by the
pyrazolyl nitrogen and thiolate sulfur donor of (L2S)- with an
Zn(1)-S(1) bond distance of 2.273(1) Å and average Npz-Zn-
(1)-S(1) and S(2)-Zn(1)-S(1) bond angles of 100.54(7) and
122.16(5)°, respectively.
[(L1OH)ZnI2] can be prepared from the [(L1O)ZnI] complex
by stoichiometric addition of HI (eq 2), resulting in protonation
[(L1O)ZnI] + HI f [(L1OH)HZnI2]
(2)
The molecular structure of [(L2S)2Zn] again confirms the
near-tetrahedral coordination geometry around the Zn with two
pyrazolyl nitrogens and two thiophenolate sulfurs from different
molecules of (L2S)- coordinated to the Zn(II) ion, leaving one
pyrazole nitrogen from each ligand uncoordinated. The thiophe-
nolate sulfurs are positioned cis to one another with a S(1)-
Zn(1)-S(2) bond angle of 112.28(9)° and an average Zn(1)-
Sthiolate bond distance of 2.291(1) Å. The pyrazolyl nitrogens
are also cis with a N(2)-Zn(1)-N(6) bond angle of 103.8(3)°
and an average Zn(1)-Npz bond distance of 2.084(5) Å. In
addition, the solid-state structure of [(L2S)2Zn] revealed two
relatively short interactions between the metal ion and the
hydrogen atoms connected to C(6) and C(28) with C(6)H‚‚‚
Zn(1) and C(28)H‚‚‚Zn(1) distances of 3.137 and 3.093 Å,
respectively.
and loss of the phenolate arm from the coordination sphere and
the addition of I- in a crude approximation of the “tyrosine
switch” mechanism.1 It appears that the Zn-Ophenol bond is
relatively weak and is easily removed by protonation. Attempts
to prepare five coordinate Zn complexes of L1O- starting from
[(L1O)ZnCH3] and bidentate HX reagents such as acetohydrox-
amic acid or hydroxyacetone met with failure. In the former
case the phenolate arm was again protonated and the complex
demetalated to produce free ligand and ZnX2 while in the latter
case it failed react at all.
The reaction of [(L1O)ZnSPh] and [(L1O)ZnSBz] with
iodomethane in CDCl3 or DMSO-d6 yields the thioether and
[(L1O)ZnI] as the alkylation products (eq 3).
[(L1O)ZnSR] + CH3I f [(L1O)ZnI] + CH3SR (3)
Synthesis and Reactivity. Reaction of 1 equiv of the
deprotonated ligand L1O- or L2S- with ZnCl2 in acetonitrile
produced the desired pseudotetrahedral LZnCl complexes. Other
derivatives could be produced either by metathesis or reaction
with silver salts of the desired ligand X to produce LZnX
species. However in our hands the most useful synthon proved
to be LZnCH3 which was produced rapidly, in high yield and
a high state of purity, from reaction of Zn(CH3)2 with either
L1OH or L2SH in toluene. For L1O- reaction of the resulting
methyl derivative with exogenous ligands, HX containing an
acidic proton with a pKa below ca. 9, proceeded with the
evolution of methane and production of LZnX species. For
ligands with pKa values near this cutoff the success of the
reaction appears to depend on the relative thiophilicity of Zn.
Thus thiophenol or benzyl mercaptan cleanly produced the
desired products within minutes while phenol itself did not react
over a several day period.
Efforts to prepare LZnOH complexes by a variety of means
with either L1O- or L2S- have thus far been unsuccessful. In
the case of [(L1O)ZnCl], metathesis with KOH or (TBA)OH
in a variety of solvents led only to demetalation and isolation
of the free protonated ligand. Attempts to protonate [(L1O)-
ZnCH3] with water were also unsuccessful, as this complex was
completely unreactive toward water. In contrast the thiopheno-
late complex, [(L2S)ZnCH3], was exceedingly reactive with
water resulting in complete decomposition to products occurring
within minutes to hours in solvents that were not rigorously
The thioether product is not coordinated to the Zn ion as
determined by NMR. The reaction of [(L1O)ZnSBz] was >90%
complete in less than 24 h, which is similar to the rate reported
by Vahrenkamp for the corresponding tris(pyrazolyl)borate
complex. The thiophenolate complex [(L1O)ZnSPh], however,
reacted ca. 7× slower. The choice of solvent used did not
materially affect the rate of either reaction. Attempts to follow
the reaction of [(L2S)ZnSPh] with methyl iodide in either CDCl3
1
or DMSO-d6 by H NMR spectroscopy were confounded by
the formation of multiple products. Attempts to sort out this
reaction are still in progress.
Discussion
Mixed nitrogen-thiolate coordination to Zn, once thought
only to be found in structural sites such as “zinc finger” proteins
and recently some prokaryotic metallothionines,28 is now
recognized as having a much wider role with an enzymatic
function as well. Mixed N2OS coordination for example is found
in T7 lysozyme, bovine 5-aminolevulinate dehydratase, and
peptide deformylase, where a pseudotetrahedral Zn is coordi-
nated to two histidine nitrogens and a cysteinyl sulfur with water
occupying the fourth position.1 An NO3S donor set characterizes
farnesyl transferase,29 and the NOS2 coordination sphere is
represented by cobalamin independent methionine synthase
(27) Burth, R.; Vahrenkamp, H. Inorg. Chim. Acta 1998, 282, 193.

Pseudotetrahedral N2O and N2S Zn(II) Complexes
Inorganic Chemistry, Vol. 38, No. 20, 1999 4599
(MetE)30 and liver alcohol dehydrogenase.1 While mixed N2O
coordination, where the oxygen donors come from aspartate or
glutamate residues, are common in Zn metalloproteins, tyrosine
phenolate oxygen donors are less so but are known to exist in
the Zn endopeptidases, astacin and the serralysins.1 Comparison
between the Zn-donor atom bond lengths found in these
complexes and various zinc metalloproteins reveals the expected
similarities with a few exceptions. The average Zn(1)-OPh
distance for these complexes of 1.911(4) Å is considerably
shorter than the Zn-OTyr bond distances (∼3.0 Å) reported for
serratia protease and alkaline protease.31,32 However, the average
Zn-Npz for the complexes containing (L1O)- is 2.06(2) Å and
is only slightly shorter than the Zn-NHis bond length of many
zinc metalloproteins (∼2.1 Å).1 The intermediate carboxylate
coordination seen in the acetate moiety of [(L1O)ZnOAc]
resembles that found in bacillolysin where the glutamate side
chain coordinated to the zinc has Zn-OGlu bond distances of
2.1 and 2.5 Å, respectively.33,34 The Zn(1)-Sthiolate bond for all
the complexes reported here are similar to those found in other
small molecule zinc thiolate complexes 35,36 and slightly shorter
(average Zn(1)-Sthiolate bond length 2.264(1) Å) than those
reported for Zn proteins such as cobalamin-dependent (MetH)
and cobalamin-independent (MetE) methionine synthases with
Zn-S bond distances of 2.32 and 2.31 Å, respectively.30 Thus
the L1OH and L2SH (N2O and N2S, respectively) family of
ligands reported here are in principle excellent platforms with
which to model the structure and reactivity of numerous Zn
metalloproteins.
Figure 6. Facial (A) and inverted umbrella (B) configurations of
(L2S)-.
has been observed in the analogous tris(pyrazolyl)borates.37
Moresurprising was the coordination mode found in [(L2S)2Zn]
where (L2S)- acts as an NS bidentate ligand with one of the
pyrazole nitrogens remaining uncoordinated. Also unusual in
this complex is the “inverted umbrella” configuration of the
ligand (Figure 6), which, rather than having the three donor
atoms directed away from the bridgehead carbon, has one of
the pyrazole nitrogens and the thiolate sulfur pointed in. This
conformation leads to, or perhaps is a result of, a moderate
interaction between the Zn and hydrogens H6A and H28A
connected to C(6) and C(28). Akita et al. have shown that the
agostic interaction, B-H‚‚‚Ru, in TpRu(H)(1,5-cyclooctadiene)
complexes stabilizes the “inverted umbrella” isomer of the tris-
(pyrazolyl)borate ligand.38 If these interactions can be viewed
as bonding, then the Zn takes on a pseudooctahedral geometry
and the large downfield shift of the methine bridgehead
hydrogen from about 6.9 ppm in [(L2S)ZnCH3] to 10.3 ppm in
[(L2S)2Zn] is indicative that the weak CH‚‚‚Zn interaction
persists in solution. Bouwman et. al. have recently reported an
interaction between Ni(II) and an aromatic proton, which gives
nearly identical “bond” lengths and NMR chemical shifts.39 On
the basis of the criteria described by Crabtree, however, both
of these interactions are more attributable to hydrogen bonding
than agostic interactions.40
One of the fundamental questions that we hoped to address
with this family of ligands is, given the similarities in the overall
structures of Zn metalloproteins, how does the donor set
modulate the reactivity of the pseudotetrahedral Zn(II) center.
One aspect that is reproduced by the model complexes reported
here is the relatively low affinity displayed by Zn for phenolate
oxygen coordination. In Zn proteins with this coordination, it
is manifested in long Zn-O phenolate bonds and in the tendency
of the tyrosine to be displaced by incoming substrates and
inhibitors, i.e. the tyrosine switch mechanism.1 In the complexes
of (L1O)-, the Zn-Ophenolate bond is not unusual, but attempts
to react [(L1O)ZnX] with HX species often leads to protonation
and loss of the phenolate group from the coordination sphere.
Such chemistry is not observed for the thiol analogue (L2S)-,
where the thiolate sulfur always remains coordinated. Thus while
Zn is usually classified as a “boarderline” hard metal, it displays
a high degree of thiophilicity.
From a steric point of view ligands L1OH and L2SH most
closely resemble the 3,5-dimethyltris(pyrazolyl)borates. While
the tert-butyl group at the 3 position of the phenyl ring provides
somewhat more side to side steric protection than does the single
methyl on the analogous pyrazole of TpMe2, the Zn binding
cavity is actually less deep. It is therefore somewhat remarkable
that the coordinatively saturated L2Zn “sandwich” complex is
not observed in this study despite the fact that such a species is
a thermodynamic sink with TpMe2 24
. Since such L2M complexes
are sterically capable of being formed with L1OH (we have
isolated both the Co(II) and Ni(II) analogues)21 the differences
in chemistry among L1OH, L2SH, and TpMe2 would appear to
be based more on differing inherent reactivity rather than on
steric bulk. Thus while reactions of LZnCH3 species with HX
yield only the ligand redistribution product, L2Zn, with TpMe2
L1OH and L2OH react rapidly to give LZnX complexes.
,
In addition to their “normal” and expected roles as facially
coordinating tridentate ligands, (L1O)- and (L2S)- display other
coordination modes as well. In [(L1OH)ZnI2] the phenol arm
is protonated and uncoordinated to the Zn, leaving L1OH to
act as a simple N2 bidentate ligand. Such a coordination mode
(28) Daniels, M. J.; Turner-Cavet, J. S.; Selkirk, R.; Sun, H.; Parkinson, J.
A.; Sadler, P. J.; Robinson, N. J. J. Biol. Chem. 1998, 273, 22957.
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S. Science 1997, 275, 1800.
(30) Peariso, K.; Goulding, C. W.; Huang, S.; Matthews, R. G.; Penner-
Hahn, J. E. J. Am. Chem. Soc. 1998, 120, 8410. We thank a reviewer
for communicating this result to us.
In an effort to mimic the activity toward alkyl group transfer
from appropriate donors to coordinated cysteine residues of a
number of zinc proteins including the Escherichia coli DNA
repair protein, Ada, and the cobalamin dependent and indepen-
dent methionine synthases, we have examined such reactions
(31) Hamada, K.; Hata, Y.; Katsuya, Y.; Hiramatsu, H.; Fujiwara, T.;
Katsube, Y. J. Biochem. 1996, 119, 844.
(32) Miyatake, H.; Hata, Y.; Fujii, T.; Hamada, K.; Morihara, K.; Katsube,
Y. J. Biochem. 1995, 118, 474.
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A.-S.; Jansonius, J. N. J. Mol. Biol. 1988, 199, 525.
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Biochem. 1992, 207, 781.
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1998, 17, 4884.
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W. J.; Spek, A. L.; Veldman, N.; Wocadlo, S. J. Chem. Soc., Dalton
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105.

4600 Inorganic Chemistry, Vol. 38, No. 20, 1999
Hammes and Carrano
utilizing our model compounds. The role of the zinc ion in
activating cysteine residues toward nucleophilic attack has been
the subject of considerable recent activity.41-44 In the most
seminal model study to date, Wilker and Lippard have shown
that, in reactions of Zn(SPh)42- and its derivatives with trimethyl
phosphate as the methyl donor, the thiolate dissociates from
the zinc prior to alkylation.41 Another study by Darensbourg et
al. using a solvated N2S2 tetradentate ligand complex of Zn and
methyl iodide as the alkylating agent reached conclusions which
were not inconsistent with this result.42 More recently however
evidence was presented by Vahrenkamp and co-workers for a
nondissociative mechanism in the alkylation of TpZnSR com-
plexes by a variety of methylating agents.43 We have examined
the methyl transfer reaction between methyl iodide or trimethyl
phosphate and the complexes [(L1O)ZnSPh], [Zn(L1O)SBz],
and [(L2S)ZnSPh] in both polar (DMSO) and nonpolar (CHCl3)
solvents. In either solvent there was no detectable reaction with
any of the complexes even after several weeks using the weak
methyl donor, trimethyl phosphate, while methyl iodide reacted
with all three complexes at varying rates which were indepen-
dent of solvent. Our results with methyl iodide are in accord
with those of Vahrenkamp et al.43 The lack of an appreciable
solvent dependence and the fact that the benzyl mercaptan
derivative reacted much faster than the thiophenol, despite its
significantly greater pKa, are not consistent with free thiolate
being the reactive species in a dissociative mechanism. They
do however support the intermolecular four-center Zn-S/C-X
transition state proposed by Vahrenkamp. At the same time the
sharp NMR spectra of our complexes even in DMSO, indicative
of little or no thiolate dissociation, is consistent with a lack of
any reactivity toward trimethyl phosphate. Thus it appears that
there may be several mechanisms by which Zn complexes can
modulate the reactivity of cysteine thiolates; i.e., they can control
the amount of “free” thiolate (a very powerful nucleophile) as
in the reaction of Zn(SPh)42- with trimethyl phosphate and by
analogy the Ada protein and methylated DNA or they can direct
reaction of methyl donors toward coordinated cysteines via an
intermolecular transition state.
One final point: In none of the model reactions studied to
date, including our own, has the thioether resulting from the
methylation remained in the metal coordination sphere. Vahr-
enkamp has proposed that the poor donor ability of thioethers
toward Zn(II) might be part of the driving force for these
reactions. However, it should be noted that in the Ada protein,
at least, the methylated cysteine is coordinated to the zinc and
there is at least one clear-cut example in the inorganic literature
of a Zn-coordinated thioether.14 Thus it remains unclear under
which conditions a thioether may be a Zn ligand.
Acknowledgment. This work was supported by Grants AI-
1157 from the Robert A. Welch Foundation and CHE-9726488
from the NSF. The NSF-ILI program Grant USE-9151286 is
acknowledged for partial support of the X-ray diffraction
facilities at Southwest Texas State University.
Supporting Information Available: Complete listings of atomic
positions, bond lengths and angles, anisotropic thermal parameters,
hydrogen atom coordinates, and data collection and crystal parameters
and ORTEP diagrams for all crystallographically characterized com-
plexes. This material is available free of charge via the Internet at
http://pubs.acs.org.
(41) Brand, U.; Rombach, M.; Vahrenkamp, H. J. Chem. Soc., Chem.
Commun. 1998, 2717.
(42) Grapperhaus, C. A.; Tuntutulani, T.; Reibenspies, J. H.; Darensbourg,
M. Y. Inorg. Chem. 1998, 37, 4052.
(43) Wilker, J. J.: Lippard, S. J. Inorg. Chem. 1997, 36, 969.
(44) Roehm, P. C.; Berg, J. M. J. Am. Chem. Soc. 1998, 120, 13083.
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