Inorganica Chimica Acta 363 (2010) 2163–2170

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Inorganica Chimica Acta

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Synthesis, structural studies and solubility properties of zinc(II), nickel(II) andcopper(II) complexes of bulky tris(triazolyl)borate ligands

Jessica L. Bongiovanni a, Brittany W. Rowe b, Patrick T. Fadden b, Michael T. Taylor b, Kirsten R. Wells b,Mukesh Kumar a, Elizabeth T. Papish a,*, Glenn P.A. Yap c, Matthias Zeller d

a Department of Chemistry, Drexel University, 3141 Chestnut St., Philadelphia, PA 19104, United Statesb Salisbury University, 1101 Camden Ave., Salisbury, MD 21801, United Statesc University of Delaware, Newark, DE 19716, United Statesd Youngstown State University, 1 University Plaza, Youngstown, OH 44555, United States

a r t i c l e i n f o a b s t r a c t

Article history:Received 24 October 2009Received in revised form 25 February 2010Accepted 3 March 2010Available online 7 March 2010

Keywords:Water-soluble ligandsTriazoleTris(triazolyl)borateBioinorganic modelsTransition metals

0020-1693/$ - see front matter � 2010 Published bydoi:10.1016/j.ica.2010.03.010

* Corresponding author. Tel.: +1 215 895 2666.E-mail address: elizabeth.papish@drexel.edu (E.T.

Tris(triazolyl)borate (Ttz) ligands are sterically similar to tris(pyrazolyl)borate (Tp) but complexes of Ttzshow improved solubility in water and alcohols due to their propensity for forming hydrogen bonds.Recently developed bulky tris(triazolyl)borate ligands can produce four and five coordinate transitionmetal complexes and serve as models for enzyme active sites in an aqueous environment. Herein wereport the synthesis of such complexes, i.e. (TtztBu,Me)ZnCl, (TtztBu,Me)ZnBr, (TtztBu,Me)NiCl, and(TtztBu,Me)CuCl, which were analyzed by X-ray crystallographic and spectroscopic methods [TtztBu,Me =tris(3-t-butyl-5-methyl-1,2,4-triazolyl)borate]. (TtztBu,Me)ZnCl crystallizes as two different polymorphswith cubic and monoclinic symmetry. Both polymorphs of (TtztBu,Me)ZnCl and (TtztBu,Me)ZnBr have tetra-hedral zinc atoms whereas the geometries at the metal in (TtztBu,Me)NiCl and (TtztBu,Me)CuCl are distortedtetrahedral. All complexes are methanol soluble and they also dissolve in methanol/water mixtures withup to 60% water.

� 2010 Published by Elsevier B.V.

1. Introduction

Tris(pyrazolyl)borate (Tp) ligands are an extremely versatileclass of facially coordinating N,N,N donors due to their ease of ste-ric and electronic modification [1–6]. Tp ligands form complexeswith nearly every metal on the periodic table, and these complexeshave been used for diverse coordination chemistry goals includingenzyme modeling and catalysis [3]. However, their poor water-solubility limits their usage for modeling hydrophilic enzymeactive sites and impedes green chemistry applications in waterand alcoholic solvents. Although charged groups, such as sulfonate,can be used to enhance water-solubility, anionic groups are oftengood ligands and can compete with the pyrazole donors andpreferentially bind to certain metals, thereby changing thecoordination geometry [7–12]. We therefore sought to usetris(triazolyl)borate (Ttz) ligands since the third nitrogen in eachtriazole ring would be available to accept hydrogen bonds andenhance the water-solubility while still allowing for the formationof N,N,N metal complexes [13,14].

Like the Tp ligands, the Ttz ligands (Chart 1) are sterically andelectronically tunable by modification of the R and R0 positions.

Elsevier B.V.

Papish).

Prior to our work, only hydrogen atoms and methyl groups hadbeen used in these positions since bulkier triazoles are notcommercially available and can be difficult to make. Late transitionmetal complexes of the TtzH,H and TtzMe,Me ligands generally leadto octahedrally coordinated complexes of the form ðTtzR;R0 Þ2M[13,15–18], and are thus not well suited for modeling four and fivecoordinate enzyme active sites. In the Tp literature, methyl groupsin the fifth position (R0) help reduce the likelihood of hydride trans-fer from the B-H group [19]. Thus, in a prior communication [20],we reported the first synthesis of 3-t-butyl-5-methyl-1,2,4-triazoleand of the bulky Ttz ligand K(TtztBu,Me). We have since improvedthe synthesis of 3-t-butyl-5-methyl-1,2,4-triazole and we reporthere a simpler procedure that includes fewer steps and is higheryielding. This allows us to further explore the steric and solubilityproperties of complexes with bulky Ttz ligands as compared to themore traditional Tp complexes.

Initial results show that the potassium salt of the ligand(KTtztBu,Me) is very water-soluble (99 mg/mL) [20] and Ttz transi-tion metal complexes made thus far also exhibit significant solubil-ity in water and/or alcohols [21]. Tp salts and complexes aregenerally not water-soluble, and the improved solubility of TtzR;R0

and its complexes can thus be attributed to the third nitrogen ineach triazole ring that confers water-solubility without alteringthe coordination geometry [13]. The increased water-solubility of

MNN

NNC

O2S

NN

ON

NN N

C

SO2

N N

O

M(TpmsiPr)2 (1M where M = Zn, Cu, Ni, Co, Fe, or Mn(II))

NN

NN

NN

CO3SM X

N N NN

NN

C

O2S

M X

O

M = Zn(II) X = Cl, Br, IM = Cu(I) X = CO

2 3M = Zn(II) X = Cl, Br, IM = Ni(II) X = Cl

Chart 2.

N N

N RR'

BHN N

N RR'

N N

N RR'

= (TtzR,R')-

N N

RR'

BHN N

RR'

N N

RR'

= (TpR,R')-

Chart 1.

2164 J.L. Bongiovanni et al. / Inorganica Chimica Acta 363 (2010) 2163–2170

1,2,4-triazoles is believed to be due to the third nitrogen being ableto act as an acceptor for hydrogen bonds from the solvent hydroxylgroups. Despite the steric bulk of TtztBu,Me, the third nitrogen is stillaccessible to small solvent molecules and the crystal structures ofTtz complexes frequently contain hydrogen bonds to water ormethanol (e.g. [(TtztBu,Me)ZnOAc]�H2O [20], [(TtztBu,Me)CuCO]�H2O[22] and [Na(TtztBu,Me)]�6MeOH) [21]. This propensity for hydrogenbonding interactions and the associated improved solubility inprotic solvents could be advantageous for modeling enzymes inwhich structure and function is modulated by hydrogen bondinginteractions [23–27]. In our previous work, we have demonstratedthat the B–N bonds in the Ttz ligands are stable towards water[20]. In particular, (TtztBu,Me)CuCO and (TtztBu,Me)ZnEt have beendissolved in water containing solvents for hours and days, respec-tively, and both show spectra that indicate that the complexes stayintact in water [22,28]. Thus the Ttz B–N bonds appear to be morerobust than the Tp B–N bonds.

In our experience, bulky Ttz complexes behave as j3-N,N,N do-nors and adopt geometries similar to those seen for Tp complexes.We have not seen the nitrogen in the four position bind to a metal,as is sometimes observed for coordination polymers formed fromunsubstituted triazoles [29–31]. This steric similarity allows for astraightforward prediction of the geometry of the Ttz complexesusing the vast literature on Tp and its complexes [1–6]. Enzymemodeling studies with Tp ligands in hydrophobic solvents [32,33]can be modified for the use of Ttz ligands in water or alcoholic sol-vents. Thus, bulky Ttz ligands will be ideal for modeling hydro-philic enzyme active sites and studying hydrolytic reactions inwater.

The water-solubility of Ttz complexes also does not vary asmuch with coordination geometry as it does for back bone modi-fied Tp derivatives such as tris(pyrazolyl)methanesulfonate (Tpms)[7–10] ligands. Whereas simple salts of Tpms ligands are water-soluble (e.g. LiTpmsiPr), Tpms ligands of intermediate steric bulk(eg. TpmsiPr) gave complexes with negligible solubility in waterand alcohols as the sulfonate groups were often buried betweenisopropyl groups in M(TpmsiPr)2 complexes (1, Chart 2) [11,12].Similarly, bis(pyrazolyl)acetate [34–38] ligands were found usefulfor modeling the 2-his-1-carboxylate facial triad found in many en-zymes [39], but upon binding the acetate to the metal the solubil-ity of the complex is often significantly reduced as compared withthat of the free ligand [38]. In terms of modeling facial triads of his-tidines in enzyme active sites such as carbonic anhydrase [40,41],Ttz ligands offer other advantages over tris(pyrazolyl)methanesul-fonate (Tpms) ligands wherein both N,N,N and N,N,O binding to themetal is possible as shown in structures 2 and 3, respectively(Chart 2) [9]. Similarly, a mixture of binding modes is seen withwater-soluble Cu(I) complexes of the TpmsPh ligand [42].

The initial results reported in an earlier short communicationdid not allow for a full steric comparison of Ttz and Tp complexesand did not lead to a clear pattern [20]. Two of the three previouslyreported structures [(TtztBu,Me)CoNO3 and (TtztBu,Me)CoCl] had very

similar geometries as compared to the corresponding Tp com-plexes, the third complex [(TtztBu,Me)ZnOAc] exhibited a geometrythat was different. In this work we will describe the synthesis,characterization, and solubility properties of four new divalentZn, Ni and Cu complexes of the TtztBu,Me ligand, and with this addi-tional data a full comparison now becomes viable and we believe atrend is beginning to emerge.

2. Experimental

2.1. General

NMR spectra were recorded using a 500 MHz Varian Unity Ino-va NMR. Infrared (IR) spectra were recorded on a Perkin–ElmerSpectrum One Fourier-transform infrared absorption spectrometer.High-resolution mass spectrometry was performed on a VG70SEdouble focusing, triple quadrupole mass spectrometer equippedwith FAB ionization capability. Elemental Analyses were per-formed by Robertson Microlit; analytical results are accurate to±0.3%. Electronic spectra were recorded on a Perkin–Elmer Lambda35 UV–Vis spectrophotometer in the range of 300–800 nm usingquartz cuvettes in CH2Cl2 or methanol solution (see Supplemen-tary material for typical spectra and concentrations). All reportedkmax and extinction coefficients resulted from Beer’s law plots withfive data points done in triplicate. All chemicals were purchasedfrom Aldrich or Acros and used as received. Pivalic acid hydrazidewas synthesized according to a literature procedure [43,44].

2.2. Synthesis and characterization

2.2.1. Synthesis of 3-t-butyl-5-methyl-1,2,4-triazole (HtztBu,Me, 4)See Scheme 2 for the structures of the starting materials. In a

typical procedure, 8.075 g (0.3513 mol) of sodium metal wasadded to 115 mL of anhydrous ethanol to create a sodium ethoxidesolution. 27.994 g (0.29611 mol) of acetamidine hydrochloride dis-solved in 230 mL of anhydrous ethanol was added to the sodiumethoxide solution and stirred for 1 h. The solid was removed byfiltration and 23.001 g (0.19801 mol) of pivalic acid hydrazidewas added to the filtrate and left to stir overnight under nitrogen.Solvent was removed by vacuum and a mixture containing 198 mLof xylenes and 10 mL of 1-octanol was added to the solid. This mix-ture was heated to reflux using a Dean-Stark Apparatus for 3.5 h

J.L. Bongiovanni et al. / Inorganica Chimica Acta 363 (2010) 2163–2170 2165

(until water evolution ceased) at 140 �C. The solvent was removedunder vacuum and the resulting solid was recrystallized in 125 mLof toluene. The solid obtained was isolated by vacuum filtrationand washed with 12 � 5 mL of cold diethyl ether followed by12 � 5 mL of cold pentane. The solid was oven dried for 20 minat 100 �C. HtztBu,Me was isolated in 58% yield (16.034 g,0.11519 mol). 1H NMR, 13C NMR, and IR spectra are identical tosamples of HtztBu,Me prepared previously via a different route [20].

2.2.2. Synthesis of potassium tris(3-t-butyl-5-methyl-1,2,4-triazolyl)borate (K(TtztBu,Me), 5)

In a typical procedure, KBH4 (0.333 g, 6.17 mmol) and HTztBu,Me

(5.001 g, 35.93 mmol) were combined in a flask under N2 and grad-ually heated to 200 �C. The reaction mixture generated a gas, pre-sumably H2, which was measured by water displacement. After3 h, gas evolution ceased and the melt was cooled to room temper-ature. Excess triazole was removed by performing five or moresublimations under vacuum at 115 �C until the product was pureby 1H NMR. K(TtztBu,Me) was obtained as a white solid (2.770 g)in 96% yield. 1H NMR (CDCl3): d 2.51 (s, 9H, Me), 1.31 (s, 27H,tBu). 13C NMR: d 170.78 (3-tz), 157.76 (5-tz), 32.75 (C-(CH3)3),30.11 (C-(CH3)3), 13.94 (Me). IR (KBr, cm�1): m 2920 (w, m (C–H)),2522 (w, m (B–H)), 2360 (w, m (B–H)), 1574 (w, m (C@N)). A suitableelemental analysis was not obtained. Anal. Calc.: C, 54.18; H, 8.01;N, 27.08. Found: C, 51.53; H, 7.39; N, 25.13%. The maximum water-solubility was 99 mg of K(TtztBu,Me) in 1.00 mL H2O at 25 �C.

2.2.3. Synthesis of TtztBu,MeZnCl (6)KTtztBu,Me (0.096 g, 0.21 mmol) was mixed with ZnCl2 (0.038 g,

0.28 mmol) in 10 mL of MeOH. The reaction was stirred overnight,and then the solvent was removed. The solid was dissolved inCH2Cl2 and then filtered. The solvent was removed from the filtrateand the solid was dried under vacuum to yield 0.091 g(0.017 mmol) of TtztBu,MeZnCl in 84% yield. Clear crystals for singlecrystal X-ray diffraction were grown by slow evaporation of aCH2Cl2 solution (monoclinic space group). Crystals have also beengrown from diethyl ether with the same molecular structure butwith a cubic space group. 1H NMR (CDCl3): d 2.59 (s, 9H, Me),1.47 (s, 27H, tBu). 13C NMR: d 174.00 (3-tz), 157.11 (5-tz), 33.04(C-(CH3)3), 30.15 (C-(CH3)3), 13.46 (Me) (assignments confirmedby HMQC and HMBC). IR (KBr, cm�1): m 2962 (w, m (C–H)), 2570(w, m (B–H)), 1494 (s, m (C@N)). ES-MS m/z = 525.3 (calc = 525.2),isotopic distribution of peaks fits the expected pattern. Anal. Calc.:C, 47.84; H, 7.07; N, 23.91. Found: C, 48.01; H, 7.10; N, 23.62%.

2.2.4. Synthesis of TtztBu,MeZnCl (6) in H2OKTtztBu,Me (0.049 g, 0.105 mmol) was mixed with ZnCl2 (0.032 g,

0.24 mmol) in 10 mL H2O. The reaction mixture was stirred for4 days, and the solution was then filtered. The solid obtained onthe filter paper was dried under vacuum to yield 0.016 g(0.030 mmol) of TtztBu,MeZnCl in 28% yield. 1H NMR spectra wereconsistent with TtztBu,MeZnCl prepared in MeOH.

2.2.5. Synthesis of TtztBu,MeZnBr (7)KTtztBu,Me (0.096 g, 0.21 mmol) was mixed with ZnBr2 (0.062 g,

0.28 mmol) in 10 mL of MeOH. The reaction was stirred for 6 days,and then the solvent was removed. The solid was dissolved inCH2Cl2 and then filtered. The solvent was removed from the filtrateand the remaining solid was dried under vacuum to yield 0.054 g(0.095 mmol) of TtztBu,MeZnBr in 46% yield. Clear crystals for singlecrystal X-ray diffraction were grown by slow evaporation of adiethyl ether solution. 1H NMR (CDCl3): d 2.60 (s, 9H, Me), 1.48(s, 27H, tBu). IR (KBr, cm�1): m 2962 (w, m (C–H)), 2570 (w, m (B–H)), 1493 (s, m (C@N)). FAB-MS m/z = 570.182253 [M+H]+

(calc = 570.181787), isotopic distribution of peaks fits the expected

pattern. Anal. Calc.: C, 44.12; H, 6.52; N, 22.05. Found: C, 45.06; H,6.63; N, 21.66%.

2.2.6. Synthesis of TtztBu,MeNiCl (8)KTtztBu,Me (0.097 g, 0.21 mmol) was mixed with NiCl2�6H2O

(0.093 g, 0.39 mmol) in 10 mL of MeOH. The reaction was stirredfor 2 days, and then the solvent was removed. The solid was dis-solved in CH2Cl2 and then filtered. The solvent was removed fromthe filtrate and the solid obtained was dried under vacuum to yield0.086 g (0.17 mmol) of TtztBu,MeNiCl in 79% yield. The fuschia col-ored product was dissolved in a minimal amount of CH2Cl2 andlayered with hexanes to grow violet blocks for single crystal X-ray diffraction. 1H NMR (CDCl3): broad signals consistent with aparamagnetic complex at d 4.57, 1.27. IR (KBr, cm�1): m 2961 (w,m (C–H)), 2558 (w, m (B–H)), 1489 (s, m (C@N)). FAB-MS m/z = 520.248514 [M+H]+ (calc = 520.249980), isotopic distributionof peaks fits the expected pattern; 484.1 (calc = 484.27) [M�Cl]+;381.1 (calc = 381.13) [M�tztBu,Me]+; 346.1 (calc = 346.16)[M�Cl�tztBu,Me]+. Anal. Calc.: C, 48.45; H, 7.16; N, 24.22. Found:C, 48.12; H, 7.26; N, 23.85%.

2.2.7. Synthesis of TtztBu,MeCuCl (9)KTtztBu,Me (0.101 g, 0.217 mmol) was mixed with CuCl2�2H2O

(0.047 g, 0.28 mmol) in 10 mL of MeOH. The reaction was stirredfor 2 days, and then the solvent was removed. The solid was dis-solved in CH2Cl2 and then filtered. The solvent was removed fromthe filtrate and the solid was dried under vacuum to yield 0.091 g(0.017 mmol) of TtztBu,MeCuCl in 80% yield. The orange/brownproduct was dissolved in a minimal amount of CH2Cl2 and layeredwith hexanes to grow orange blocks for single crystal X-ray diffrac-tion. 1H NMR (CDCl3): broad signals consistent with a paramag-netic complex at d 3.80, 1.28. IR (KBr, cm�1): m 2960 (w, m (C–H)),2557 (w, m (B–H)), 1494 (s, m (C@N)). FAB-MS m/z = 525.247490[M+H]+ (calc = 525.244233), isotopic distribution of peaks fits theexpected pattern; 490.1 (calc = 490.28) [M�Cl+H]+; 386.1 (calc =386.14) [M�tztBu,Me]+; 351.1 (calc = 351.17) [M�Cl�tztBu,Me]+. Anal.Calc.: C, 48.01; H, 7.10; N, 23.99. Found: C, 47.81; H, 7.06; N,23.90%.

2.2.8. Solubility measurementsSolubility testing was done by gradually adding milligram por-

tions of (TtztBu,Me)ZnCl or (TtztBu,Me)ZnBr to 500 ll of water ormethanol until no more would dissolve. Due to the high solubilityof (TtztBu,Me)NiCl and (TtztBu,Me)CuCl, solubility testing was donewith 250 ll of solvent. Solubility data is shown in Table 3. Determi-nations of solubility in methanol/water mixtures were done bytesting a fixed number of millimoles (typically 0.01 mmol) of(TtztBu,Me)MX in 1 mL solutions containing a varied percentage ofwater (10%, 20%, etc.) until the maximum amount of water thatwould still allow dissolution was found.

2.2.9. Single crystal X-ray diffraction studiesDiffraction data for all compounds were collected using a Bru-

ker AXS SMART APEX CCD diffractometer using monochromaticMo Ka radiation with the omega scan technique. Single crystalsof compounds TtztBu,MeZnCl (monoclinic), TtztBu,MeZnCl (cubic),TtztBu,MeZnBr, and TtztBu,MeCuCl were mounted on glass fibers usingviscous oil flash-cooled to 120 K. TtztBu,MeNiCl was mounted on aMitegen micromesh mount and data were collected at 100 K. Datawere collected, unit cells determined, and the data integrated andcorrected for absorption and other systematic errors using eitherthe Apex2 suite of programs [45] (for TtztBu,MeNiCl) or SMART[46], SAINT [46] and SADABS [47]. Monoclinic TtztBu,MeZnClis isostructural with TtztBu,MeCuCl, cubic TtztBu,MeZnCl withTtztBu,MeZnBr. The structures were solved by direct methods or byisomorphous replacement and refined by full matrix least squares

O

OMe

O

NNH2

NH

NH2

N N

N

58%

NH2

NH2

NaOEtEtOH

Cl

N2H4 H2O

2166 J.L. Bongiovanni et al. / Inorganica Chimica Acta 363 (2010) 2163–2170

against F2 with all reflections using SHELXTL 6.14 (for TtztBu,MeNiCl)or 6.12 (for all other compounds) [47]. All non-hydrogen atomswere refined anisotropically. Hydrogen atoms were placed incalculated positions and were refined with isotropic displacementparameters 1.2 (C–H) or 1.5 (CH3) times that of the adjacent carbonatom.

N N

N

BHN N

N

N N

N

K MX2 = ZnCl2, ZnBr2, NiCl2 6H2O, CuCl2 2H2O N N

N tBu

BH

N N

NtBu

M

KX

MeOH

X

N N

N tBu

6, 7, 8 and 95

Scheme 3.

H65%1) EtOH

2) heat, -H2OH

4

Scheme 2. A shorter route to 3-t-butyl-5-methyl-1,2,4-triazole (HtztBu,Me) (4).

3. Results and discussion

3.1. Ligand synthesis

Previously, we reported a four step synthesis of 3-t-butyl-5-methyl-1,2,4-triazole (HtztBu,Me) in which the carbon atoms origi-nated from acetonitrile and pivaloyl chloride (Scheme 1) [20]. Thissynthesis has the virtue of being very general and readily adaptableto form other 3-R-5-R0-1,2,4-triazoles, since many different nitrilesand acid chlorides are commercially available. However, the over-all yield for all four steps is just 15% [20], and so there was a cleardemand for a higher yielding procedure. As shown in Scheme 2, wehave adapted a literature procedure reported for the synthesis of 3-phenyl-5-methyl-1,2,4-triazole [48] to produce HtztBu,Me in twosteps and a 38% overall yield. This procedure can be generalizedto form many different 3-R-5-methyl-1,2,4-triazoles with variedsteric bulk in position three using commercially available estersas the starting point. From the triazole the water-soluble ligandsalt, K(TtztBu,Me), was prepared in 96% yield as described previously[20] by melting a mixture of KBH4 and HtztBu,Me in a 1:5.8 molarratio at 200 �C (see Section 2).

3.2. Synthesis of transition metal complexes 6–9

Transition metal complexes 6–9 were prepared in yields of 46–84% from the appropriate metal salts with methanol as the solvent,followed by removal of the methanol and extraction of the productinto methylene chloride (Scheme 3). All compounds were charac-terized and their structures unambiguously assigned using IR, ESor FAB-MS, and single crystal X-ray diffraction. (TtztBu,Me)ZnCl crys-tallized from diethyl ether and methylene chloride as two differentpolymorphs, see the discussion of the single crystal structures be-low for details. In addition, 1H NMR spectroscopy was used to con-firm the structure of the diamagnetic zinc complexes and for(TtztBu,Me)ZnCl the 13C NMR resonances were assigned using HMQCand HMBC.

Due to our interest in green chemistry, we have also prepared(TtztBu,Me)ZnCl in water thus avoiding organic solvents. ZnCl2 andK(TtztBu,Me) are both water-soluble and they react in water to yieldKCl(aq) and (TtztBu,Me)ZnCl. (TtztBu,Me)ZnCl is slightly soluble inwater and precipitates out of solution, thus providing a drivingforce for the reaction to proceed. The yield in water (28%) was ob-tained by simple filtration (i.e. without extraction to avoid the useof organic solvents) and is significantly lower than in MeOH (84%),but it provides proof of principle that water-soluble ligands can en-

Me C N

NH2

OEt

Cl NH

OEt

N

EtO C(CH3)3

O(CH3)3CCOCl

Et3N, toluene

Et3NHCl

H2NNH2CH2Cl2-H2O N N

N

H

CH2Cl2

NaOH (aq)Toluene

EtOHHCl (g)

4

-NaCl -H2O

-EtOH

Scheme 1. Our published route to 3-t-butyl-5-methyl-1,2,4-triazole (HtztBu,Me) (4)[20].

able the development of more environmentally friendly synthesesperformed in water instead of organic solvents.

3.3. Crystal structures of transition metal complexes 6–9

Single crystal diffraction of all four compounds led to the forma-tion of three distinct structures (Tables 1 and 2, Figs. 1 and 2, andSupplementary Figs. S1–S3). The (TtztBu,Me)ZnCl complex yielded,when crystallized from diethyl ether and methylene chloride,two different polymorphs: a cubic and a monoclinic form (Fig. 1and Supplementary Fig. S1, respectively). Both structures are sol-vent free and the molecules in both structures are chemically iden-tical with nearly equivalent bond lengths, angles and dihedralangles. The differences between the two polymorphs are thus so-lely based on the packing arrangement of the molecules withinthe crystal. Given similar energetics for the two packing arrange-ments slight differences in the crystallization procedures can easilylead to the formation of different polymorphs and crystals with thesame molecular structure and different packing arrangements arenot uncommon [49,50]. Interestingly two of the other compoundsreported herein are isostructural with each one of the polymorphsof (TtztBu,Me)ZnCl. (TtztBu,Me)CuCl crystallized in a monoclinic set-ting with similar cell parameters and atom positions as for mono-clinic (TtztBu,Me)ZnCl, and (TtztBu,Me)ZnBr is isostructural to cubic(TtztBu,Me)ZnCl. With both polymorphs realized twice the two alter-native ways to pack the copper and zinc complexes are thus clearlyenergetically comparable. The packing efficiencies in the mono-clinic and cubic settings for these four compounds are not decisive:the volumes per molecule obtained from the crystal data vary byless than two percent and the largest and smallest volumes(678.5 and 667.75 ÅA

03) are found for the two monoclinic cells. The

(TtztBu,Me)NiCl complex, which crystallizes in an orthorhombic set-ting, shows a packing coefficient at the lower end of the range ob-tained for the other four compounds (667.23 ÅA

03, collected at a 20 K

lower temperature).

3.4. Steric and electronic comparison of TtztBu,Me and analogous Tpligands

The zinc atoms in both forms of (TtztBu,Me)ZnCl and in(TtztBu,Me)ZnBr are in tetrahedral environments and the bond

Table 1Crystallographic data for (TtztBu,Me)ZnCl (6), (TtztBu,Me)ZnBr (7), (TtztBu,Me)NiCl (8), and (TtztBu,Me)CuCl (9).

(TtztBu,Me)ZnCl (6cubic) (TtztBu,Me)ZnCl (6monoclinic) (TtztBu,Me)ZnBr (7) (TtztBu,Me)NiCl (8) (TtztBu,Me)CuCl (9)

Formula C21H37BClN9Zn C21H37BClN9Zn C21H37BBrN9Zn C21H37BClN9Ni C21H37BClCuN9

Formula weight 527.23 527.23 571.68 520.57 525.40Color/habit colorless/block colorless/block colorless/block violet-red/block orange/blockCrystal system cubic monoclinic cubic orthorhombic monoclinicSpace group I-43d P21/m I-43d Aba2 P21/m

a (ÅA0

) 22.040(3) 9.330(3) 22.097(2) 30.222(3) 8.973(2)

b (ÅA0

) 22.040(3) 15.736(5) 22.097(2) 14.9943(16) 16.722(4)

c (ÅA0

) 22.040(3) 9.638(3) 22.097(2) 11.7792(12) 9.498(3)

a (�) 90 90 90 90 90b (�) 90 106.471(4) 90 90 110.434(3)c (�) 90 90 90 90 90

V (ÅA0

3) 10706(2) 1357.0(8) 10789(2) 5337.8(10) 1335.5(6)

Z 16 2 16 8 2Dcalcd (g cm�3) 1.308 1.290 1.408 1.296 1.307l (mm�1) 1.044 1.030 2.418 0.854 0.944F(0 0 0) 4448 556 4736 2208 554Crystal dimensions (mm) 0.40 � 0.38 � 0.35 0.17 � 0.10 � 0.07 0.39 � 0.21 � 0.12 0.43 � 0.40 � 0.24 0.39 � 0.34 � 0.23T (K) 120(2) 120(2) 120(2) 100(2) 120(2)

k (ÅA0

) 0.71073 0.71073 0.71073 0.71073 0.71073

h (�) 2.26–28.29 2.20–27.49 2.26–28.32 1.35–28.28 2.29–28.28No. of measured reflections 28 911 10 819 59 510 26 057 16 319No. of observed reflections 2164 3148 2256 6622 3413Goodness-of-fit (GOF) 1.021 1.022 1.002 1.103 1.061Final R indices [I > 2rI] R1 (%)a 3.82 3.78 4.14 3.25 2.99wR2 (%)a 7.52 10.23 12.25 7.57 8.34

a Quantity minimized ¼ RðwF2Þ ¼ fP½wðF2

o � F2c Þ

2�=PðwF2

oÞ2g1=2 : RðFÞ ¼

PD=PðFoÞ; D ¼ jðFo � FcÞj : w ¼ ½r2ðF2

oÞ þ ðaPÞ2 þ bP��1 : P ¼ ½2F2c þMaxðFo; 0Þ�=3.

Table 2Selected bond lengths (Å) and angles (deg) for (TtztBu,Me)ZnCl (6), (TtztBu,Me)ZnBr (7),(TtztBu,Me)NiCl (8), and (TtztBu,Me)CuCl (9).

Bond lengths Bond angles

(TtztBu,Me)ZnCl (6cubic)Zn–N1 2.053(2) N1–Zn–N1 93.43(9)Zn–Cl 2.1728(14) N1–Zn–Cl 122.80(6)

(TtztBu,Me)ZnCl (6monoclinic)Zn–N4 2.031(3) N1–Zn–N4 94.03(7)Zn–N1 2.0438(19) N1–Zn–N1 92.24(10)Zn–Cl 2.1738(11) N4–Zn–Cl 121.61(8)

N1–Zn–Cl 123.39(5)

(TtztBu,Me)ZnBr (7)Zn–N1 2.056(3) N1–Zn–N1 93.73(12)Zn–Br 2.2794(11) N1–Zn–Br 122.58(9)

(TtztBu,Me)NiCl (8)Ni1–N1 1.9872(16) N1–Ni1–N7 91.88(7)Ni1–N4 2.0052(16) N1–Ni1–N4 90.55(7)Ni1–N7 2.0005(18) N7–Ni1–N4 94.49(7)Ni1–Cl1 2.1847(6) N1–Ni1–Cl1 130.56(5)

N7–Ni1–Cl1 119.10(5)N4–Ni1–Cl1 121.13(5)

(TtztBu,Me)CuCl (9)Cu–N1 2.0653(12) N4–Cu–N1 89.22(5)Cu–N4 1.9208(17) N1–Cu–N1 102.51(6)Cu–Cl 2.1567(7) N4–Cu–Cl 145.75(5)

N1–Cu–Cl 111.31(3)

Fig. 1. Molecular diagram of (TtztBu,Me)ZnCl (cubic). Ellipsoids are shown at 30%probability and H atoms are omitted for clarity.

J.L. Bongiovanni et al. / Inorganica Chimica Acta 363 (2010) 2163–2170 2167

lengths and angles are generally very similar to those of their Tpanalogs: (TptBu)ZnCl and (TptBu)ZnBr (within 0.01 Å or 1�) [51].The one exception is that the Zn–Br bond in (TptBu)ZnBr is slightlylonger at 2.325(1) Å [51] compared with the value of 2.2794(11) Åobtained for 7.

Unlike the zinc complexes, the nickel atom in (TtztBu,Me)NiCl isdistorted slightly from an ideal tetrahedral environment and thismolecule lacks an approximate C3 axis. The bond lengths and an-gles of (TtztBu,Me)NiCl can be compared with the two reported

structures for (TptBu,Me)NiCl [52,53]; the latter [53] provides a moreaccurate data set for comparison with (TtztBu,Me)NiCl. The corre-sponding bond lengths in (TptBu,Me)NiCl [53] and (TtztBu,Me)NiClare generally within �0.01 Å of each other, but the Ni–Cl distanceof 2.2077(9) Å for (TptBu,Me)NiCl is �0.02 Å larger than the corre-sponding Ni1–Cl1 distance in (TtztBu,Me)NiCl of 2.1847(6) Å. How-ever, (TptBu,Me)NiCl crystallizes in a different space group (R3m)and the molecule has C3v symmetry (all pyrazole rings are

Fig. 2. Molecular diagram of (TtztBu,Me)CuCl. Ellipsoids are shown at 30% probabilityand H atoms are omitted for clarity.

Table 3Solubility data for (TtztBu,Me)ZnCl (6), (TtztBu,Me)ZnBr (7), (TtztBu,Me)NiCl (8), and(TtztBu,Me)CuCl (9).

Compound Water-solubility

Methanolsolubility

Methanol/water-solubility

(TtztBu,Me)ZnCl(6)

<2 mg/mL 28 mg/mL(0.053 mmol/mL)

5.2 mg/mL (0.010 mmol/mL) in 80%/20%

(TtztBu,Me)ZnBr(7)

<2 mg/mL 20 mg/mL(0.035 mmol/mL)

5.6 mg/mL (0.010 mmol/mL) in 80%/20%

(TtztBu,Me)NiCl(8)

<2 mg/mL 136 mg/mL(0.261 mmol/mL)

5.1 mg/mL (0.010 mmol/mL) in 40%/60%

(TtztBu,Me)CuCl(9)

<2 mg/mL 140 mg/mL(0.267 mmol/mL)

5.1 mg/mL (0.010 mmol/mL) in 40%/60%

2168 J.L. Bongiovanni et al. / Inorganica Chimica Acta 363 (2010) 2163–2170

equivalent). In contrast, (TtztBu,Me)NiCl crystallizes in the Aba2space group and has C1 symmetry with the triazole rings inequiv-alent, although all the Ni–N bond lengths are similar. The bond an-gles for (TtztBu,Me)NiCl (Table 2) range from 119.10(5) to 130.56(5)�for Cl–Ni–N and 90.55(7)� to 94.49(7)� for N–Ni–N whereas thecorresponding angles in (TptBu,Me)NiCl are 122.93(5)� and93.26(6)� [53]. Clearly the bond angles are similar in magnitudebut (TtztBu,Me)NiCl has lower symmetry than (TptBu,Me)NiCl.

(TtztBu,Me)CuCl also lacks a rotational C3 axis, but it does possessa mirror plane that intersects the Cu–Cl bond and it has Cs symme-try. In contrast to the zinc complexes (TtztBu,Me)ZnCl and(TtztBu,Me)ZnBr which have the metal halide bond along the axis be-tween the boron and the metal, for (TtztBu,Me)CuCl (and(TtztBu,Me)NiCl) the distortion from tetrahedral geometry movesthe halide far off of that line. This geometry is also seen for the cor-responding Tp complexes; (TptBu,Me)CuCl [54] has bond lengths andangles within �0.01 Å or 3� of the corresponding values in(TtztBu,Me)CuCl, and the two structures look nearly superimposable.Therefore, the deviation from tetrahedral geometry is more a func-tion of the metal than the ligand and the coordination environmentobserved is not unique to the TtztBu,Me ligand.

We now have synthesized and obtained crystal structures on aseries of eight TtztBu,Me transition metal complexes for which anal-ogous TptBu,Me or TptBu complexes were structurally characterized.For seven of these eight complexes, namely (TtztBu,Me)ZnCl,(TtztBu,Me)ZnBr, (TtztBu,Me)CuCl, (TtztBu,Me)CuCO [22], (TtztBu,Me)NiCl,(TtztBu,Me)CoCl [20], and (TtztBu,Me)CoNO3 [20], the structures arevery similar to those of their TptBu,Me or TptBu analogs in terms ofbond lengths, bond angles, and overall coordination geometry.Only for (TtztBu,Me)Zn(OAc), which has a bidentate acetate withone oxygen weakly bound to the zinc [20], do we see a significantdifference in coordination geometry since (TptBu,Me)Zn(OAc) clearlyhas a monodentate acetate ligand [55]. Based on our recent analy-

sis of the electron donor ability of the TtztBu,Me ligand [22], the elec-tronic difference between these ligands is slight since thefrequency of the CO stretching vibration shifts by �20 cm�1 be-tween (TptBu,Me)CuCO [56,57] and (TtztBu,Me)CuCO. Shifts in theCO stretching vibration of a similar magnitude are observed byadding alkyl groups to the Tp ligand [22]. Nonetheless, this modestelectronic effect is enough to change the coordination geometry atzinc. Since TtztBu,Me is a weaker electron donor than TptBu,Me, thezinc in (TtztBu,Me)Zn(OAc) is slightly more electropositive andthe acetate becomes bidentate due to electrostatic attraction tothe zinc.

Similar increases in coordination number were observed upongoing from alkyl substituted Tp complexes to CF3 substituted Tpcomplexes. For example, [TpMe,MeCu]2 and [TpiPr,iPrCu] both havethree coordinate copper ions and [TpH,HCu]2 is four coordinate[58,59]. In addition, all of these TpCu complexes fail to coordinateneutral O donors like acetone, methanol and water [58]. Incontrast, a fluorinated ligand causes the coordination of dimethyl-acetamide (DMAC) to form a four coordinate complex,TpCF3 ;CF3 CuðDMACÞ [60]. Electronic differences are responsible sincethe CF3 group is sterically larger than a methyl group but smallerthan an isopropyl group. This indicates that a more electron defi-cient ligand can increase the coordination number at the metal,as we have seen for TtztBu,MeZnOAc [20].

Overall, we see very similar coordination geometries for isoster-ic Tp and Ttz complexes; the only difference (betweenTtztBu,MeZnOAc and TptBu,MeZnOAc) seems to be due to electronicsrather than sterics. Thus the TtztBu,Me ligand is sterically very sim-ilar to the TptBu,Me ligand. This is a tremendous advantage of thisnew class of ligands as it allows predictions of the geometry ofTtz complexes beforehand from the corresponding Tp complexeswhen using the new complexes in enzyme modeling studies.

3.5. Solubility properties of TtztBu,Me complexes

Despite their steric similarities the Ttz ligands differ signifi-cantly from the Tp ligands in terms of their solubility in waterand other hydrophilic solvents. As may be expected for a salt,KTtztBu,Me is very water-soluble (99 mg/mL) [20]. Its complexes de-scribed herein [(TtztBu,Me)ZnCl, (TtztBu,Me)ZnBr, (TtztBu,Me)CuCl, and(TtztBu,Me)NiCl] are only slightly soluble in water (<2 mg/mL), butthey all readily dissolve in methanol to varying extents (Table 3).With the zinc complexes a maximum of 28 mg and 20 mg of(TtztBu,Me)ZnCl and (TtztBu,Me)ZnBr, respectively, could be dissolvedin 1 mL of methanol. In methanol solutions that contain up to 20%water only milligram quantities of these complexes dissolve (Table3). In contrast, (TtztBu,Me)CuCl and (TtztBu,Me)NiCl are very soluble inmethanol (>136 mg of each will dissolve in 1 mL of methanol) andthey readily dissolve in methanol/water mixtures with up to 60%water (Table 3).

These solubility differences can be rationalized in terms ofstructure. In contrast to the high water-solubility of the salt,

J.L. Bongiovanni et al. / Inorganica Chimica Acta 363 (2010) 2163–2170 2169

KTtztBu,Me, which has solvent accessible charged moieties, com-plexes 6–9 have low water-solubility. The crystal structures of 6–9 show that the transition metal ion and the halide are buried bythe t-butyl groups. Clearly, the copper and nickel complexes (8and 9) show better solubility in methanol and methanol/waterthan the zinc complexes (6 and 7). Complexes 8 and 9 change colorupon dissolving in these solvents, suggesting a change in coordina-tion geometry or donor set. These changes have been investigatedquantitatively, as described below, by measuring UV–Vis spectra inCH2Cl2 (in which the color and the geometry should be the same asthe solid state) and methanol. Coordinated solvent molecules areconsistent with our UV–Vis data and could add sites for hydrogenbonding and explain the enhanced solubility of these complexes.However, attempts to crystallize a methanol or water complex of8 or 9 gave only crystals with unit cell parameters identical to sol-vent free 8 and 9, so solvent coordination appears to occur only inthe solution phase.

The solubility of 6–9 in methanol and methanol/water mixturesis due to the third nitrogen in the triazole rings that can hydrogenbond to protic solvents. This represents an improvement over thecorresponding Tp complexes, which are generally only soluble inorganic aprotic solvents [13,61]. These properties make Ttz ligandswell suited for hydrolytic reactions as well as for designing struc-tural and functional mimics for hydrophilic enzyme active sites.The Ttz ligands can also be used to take well known catalytic pro-cesses that involve Tp ligands and adapt them to green chemistryapplications in water or alcoholic solvents.

3.6. Electronic spectra of (TtztBu,Me)CuCl (9) and (TtztBu,Me)NiCl (8)

The electronic spectra show d–d transitions and a ligand tometal charge transfer (LMCT) band in the visible and UV regionsof the spectra, respectively (Table 4). The Cu(II) complex 9 inCH2Cl2 (Fig. S4) shows an LMCT absorption at 389 nm and justone d–d transition at 509 nm as expected for a d9 tetrahedralcomplex, the latter absorbance is broad and obscured by theshoulder of the much stronger LMCT band. The Ni(II) complex8 in CH2Cl2 (Fig. S6) exhibits an LMCT band and two d–d transi-tions in the visible region (the expected third d–d transition fora d8 tetrahedral complex is probably in the near infrared). Themolar absorptivities for both 8 and 9 in CH2Cl2 are consistentwith a tetrahedral geometry [62], but in methanol the absorben-cies decrease substantially and much higher concentrations wereneeded. For the Cu complex 9 in methanol (Fig. S5), the entirespectrum appears to be obscured by the shoulder of a strongabsorption below 300 nm. Useful information cannot be readilyextracted from the spectra of 9 in methanol, except to say thatthe coordination geometry has clearly changed, mostly likely toa higher coordination number. For the Ni complex 8 in methanol(Fig. S7), d–d transitions are still seen at about the same wave-lengths as in CH2Cl2, but they are much weaker in intensity anda new peak is present at 410 nm. If mononuclear Ni complexesare formed when 8 dissolves in methanol (which seems likely

Table 4UV–Vis data for (TtztBu,Me)NiCl (8) and (TtztBu,Me)CuCl (9). Values of kmax are given innm and e is given in M�1 cm�1.

kmax (e) in CH2Cl2

(TtztBu,Me)NiCl (8) 327 (650) (LMCT, shoulder)494 (458) (d–d)576 (�150) (d–d, broad shoulder)

(TtztBu,Me)CuCl (9) 312 (1860) (p–p*)389 (1210) (LMCT)509 (<200) (d–d, weak, broad)

given steric bulk of the ligand), then a value of e = 18 M�1 cm�1

at kmax = 490 nm can be calculated and suggests an octahedralNi(II) due to methanol coordination. Extinction coefficients lessthan 80 M�1 cm�1 are consistent with an octahedral geometry[63] since d–d transitions are forbidden under the Laporte selec-tion rule. Note that the complexes 8 and 9 were originally syn-thesized in methanol and have be isolated from methanol inpure form after the UV–Vis studies, so this rules out decomposi-tion of these complexes in methanol.

4. Conclusions

The structures reported herein for (TtztBu,Me)ZnCl, (TtztBu,Me)ZnBr,(TtztBu,Me)NiCl, and (TtztBu,Me)CuCl add to the evidence thatTtztBu,Me is sterically very similar to the TptBu,Me and TptBu ligands.For the majority (seven out of eight) of the reported TtztBu,Me

complexes [20,22] the bond lengths, angles and coordinationgeometries are remarkably similar to those seen in the isostericTp complexes. However, a slight decrease in electron donor abil-ity [22] for TtztBu,Me relative to TptBu,Me might be responsiblefor a change in coordination geometry for one complex,(TtztBu,Me)ZnOAc [20], which has a bidentate acetate ligandwhereas the corresponding Tp complex has a monodentate acetate[55]. Therefore, TtztBu,Me is a good steric analog of TptBu,Me but it iselectronically a slightly weaker donor. It has dramatically im-proved solubility properties and TtztBu,Me complexes can even besynthesized in water without the use of organic solvents. In severalinstances [20–22], the Ttz complexes have been shown to hydro-gen bond to methanol or adventitious water molecules. This pro-pensity for hydrogen bonding is believed to contribute to theimproved solubility in water and alcohols displayed by theTtztBu,Me and TtzPh,Me ligands and their complexes [21]. All ofthe Ttz complexes described thus far are four or five coordinateand the bulky Ttz ligands thus have the potential to lead to goodstructural models for metalloenzymes. Control of the coordinationgeometry at the metal through bulky ligands has thus beencoupled with solubility in protic, hydrogen bonding solvents in away that was not possible with Tp ligands. Therefore, these ligandsand complexes show promise for hydrolytic chemistry, modelinghydrophilic enzyme active sites, catalysis, and green chemistryapplications.

Acknowledgements

The authors thank the ACS Petroleum Research Fund for start upGrant 435120, NSF CAREER, and Drexel and Salisbury Universitiesfor financial support; and Dr. G.M. Ferrence and Dr. A.W. Addisonfor helpful discussions and Natalie Dixon, April Holcomb, andTim Wade for assistance with experiments. The diffractometerused to solve the structure of 8 was funded by NSF Grant0087210, by Ohio Board of Regents Grant CAP-491, and by YSU.

Appendix A. Supplementary material

CCDC 725456, 725457, 725458, 725459 and 725649 contain thesupplementary crystallographic data for this paper. These data canbe obtained free of charge from The Cambridge CrystallographicData Centre via www.ccdc.cam.ac.uk/data_request/cif. Supplemen-tary data associated with this article can be found, in the onlineversion, at doi:10.1016/j.ica.2010.03.010.

References

[1] S. Trofimenko, J. Am. Chem. Soc. 88 (1966) 1842.[2] S. Trofimenko, Chem. Rev. 93 (1993) 943.

2170 J.L. Bongiovanni et al. / Inorganica Chimica Acta 363 (2010) 2163–2170

[3] S. Trofimenko, Scorpionates: The Coordination Chemistry of Polypyrazolylb-orate Ligands, Imperial College Press, London, 1999. and references therein.

[4] G. Parkin, Chem. Commun. (2000) 1971.[5] H. Vahrenkamp, Acc. Chem. Res. 32 (1999) 589.[6] C. Pettinari, Scorpionates II: Chelating Borate Ligands, World Scientific

Publishing Co., Singapore, 2008.[7] W. Kläui, M. Berghahn, G. Rheinwald, H. Lang, Angew. Chem., Int. Ed. 39 (2000)

2464.[8] W. Kläui, D. Schramm, W. Peters, G. Rheinwald, H. Lang, Eur. J. Inorg. Chem.

(2001) 1415.[9] W. Kläui, M. Berghahn, W. Frank, G.J. Reiß, T. Schönherr, G. Rheinwald, H. Lang,

Eur. J. Inorg. Chem. (2003) 2059.[10] C. Santini, M. Pellei, G.G. Lobbia, A. Cingolani, R. Spagna, M. Camalli, Inorg.

Chem. Commun. 5 (2002) 430.[11] E.T. Papish, M.T. Taylor, F.E. Jernigan, M.J. Rodig, R.R. Shawhan, G.P.A. Yap, F.A.

Jové, Inorg. Chem. 45 (2006) 2242.[12] F.E. Jernigan, F.A. Jové, E.T. Papish, G.P.A. Yap, Acta Crystallogr. E 62 (2006)

m3172.[13] S. Trofimenko, J. Am. Chem. Soc. 89 (1967) 3170.[14] A similar approach has been used with tris(imidazolyl)phosphane ligands, see:

P.C. Kunz, G.J. Reiß, W. Frank, W. Kläui, Eur. J. Inorg. Chem. (2003) 3945.[15] G.G. Lobbia, M. Pellei, C. Pettinari, C. Santini, B.W. Skelton, A.H. White, Inorg.

Chim. Acta 358 (2005) 1162. and references therein.[16] K.B. Shiu, W.N. Guo, S.M. Peng, M.C. Cheng, Inorg. Chem. 33 (1994) 3010. and

references therein.[17] C. Janiak, T.G. Scharmann, S.A. Mason, J. Am. Chem. Soc. 124 (2002) 14010. and

references therein.[18] Z. Xiao, R.W. Gable, A.G. Wedd, C.G. Young, J. Am. Chem. Soc. 118 (1996) 2912.

and references therein.[19] C. Bergquist, L. Koutcher, A.L. Vaught, G. Parkin, Inorg. Chem. 41 (2002) 625.[20] F.E. Jernigan, N.A. Sieracki, M.T. Taylor, A.S. Jenkins, S.E. Engel, B.W. Rowe, F.A.

Jové, G.P.A. Yap, E.T. Papish, G.M. Ferrence, Inorg. Chem. 46 (2007) 360.[21] S.R. Gardner, E.T. Papish, W.H. Monillas, G.P.A. Yap, J. Inorg. Biochem. 102

(2008) 2179.[22] E.T. Papish, T.M. Donahue, K.R. Wells, G.P.A. Yap, Dalton Trans. (2008) 2923.[23] D.W. Christianson, J.D. Cox, Annu. Rev. Biochem. 68 (1999) 33.[24] J.H. Cho, D.H. Kim, D.-H. Kim, K.J. Lee, K.Y. Choi, Biochemistry 40 (2001) 10197.[25] Y. Lu, J.S. Valentine, Curr. Opin. Struct. Biol. 7 (1997) 495.[26] Y. Lu, T.D. Pfister, Metal Ions Life Sci. (Ubiquitous Roles of Cytochrome P450

Proteins) 3 (2007) 267.[27] M.S. Rogers, E.M. Tyler, N. Akyumani, C.R. Kurtis, R.K. Spooner, S.E. Deacon, S.

Tamber, S.J. Firbank, K. Mahmoud, P.F. Knowles, S.E.V. Phillips, M.J. McPherson,D.M. Dooley, Biochemistry 46 (2007) 4606.

[28] M. Kumar, E.T. Papish, M. Zeller, A.D. Hunter, Dalton Trans. 39 (2010) 59.[29] J.G. Haasnoot, Coord. Chem. Rev. 200–202 (2000) 131.[30] A. Tian, J. Ying, J. Peng, J.-Q. Sha, H.-J. Pang, P.-P. Zhang, Y. Chen, M. Zhu, Z.-M.

Su, Inorg. Chem. 48 (2009) 100.[31] Q.-G. Zhai, X.-Y. Wu, S.-M. Chen, C.-Z. Lu, W.-B. Yang, Cryst. Growth Des. 6

(2006) 2126.[32] S. Hikichi, M. Tanaka, Y. Moro-oka, N. Kitajima, J. Chem. Soc., Chem. Commun.

(1992) 814.

[33] N. Kitajima, M. Osawa, N. Tamura, Y. Moro-oka, T. Hirano, M. Hirobe, T.Nagano, Inorg. Chem. 32 (1993) 1879.

[34] A. Beck, B. Weibert, N. Burzlaff, Eur. J. Inorg. Chem. (2001) 521.[35] A. Beck, A. Barth, E. Hübner, N. Burzlaff, Inorg. Chem. 42 (2003) 7182.[36] I. Hegelmann, A. Beck, C. Eichhorn, B. Weibert, N. Burzlaff, Eur. J. Inorg. Chem.

(2003) 339.[37] N. Burzlaff, I. Hegelmann, B. Weibert, J. Organomet. Chem. 626 (2001) 16.[38] B.S. Hammes, M.T. Kieber-Emmons, J.A. Letizia, Z. Shirin, C.J. Carrano, L.N.

Zakharov, A.L. Rheingold, Inorg. Chim. Acta 346 (2003) 227.[39] X. Shan, L. Que Jr., J. Inorg. Biochem. 100 (2006) 421.[40] C.A. Fierke, J.F. Krebs, R.A. Venters, in: F. Botre, G. Gros, T.B. Storey (Eds.),

Carbonic Anhydrase, VCH Publishing Inc., Weinheim, 1991.[41] G. Parkin, Chem. Rev. 104 (2004) 699. and references therein.[42] R. Wanke, P. Smolenski, M.F.C. Guedes da Silva, L.M.D.R.S. Martins, A.J.L.

Pombeiro, Inorg. Chem. 47 (2008) 10158.[43] K. Ohmoto, T. Yamamoto, M. Okume, T. Horiuchi, H. Imanishi, Y. Odagaki, K.

Kawabate, T. Sekioka, Y. Hirota, S. Matsuoka, H. Nakai, M. Toada, J.C. Cheronis,L.W. Spruce, A. Gyorkos, M. Wieczorek, J. Med. Chem. 44 (2001) 1268.

[44] Also, for the synthesis of related hydrazides see: K.M. Khan, M. Rasheed, Z.Ullah, S. Hayat, F. Kaukab, M.I. Choudhary, A.U. Rahman, S. Perveen, Bioorg.Med. Chem. 11 (2003) 1381.

[45] Bruker, Apex2 v2.1-4, Bruker AXS Inc., Madison (WI), USA, 2007.[46] Bruker Area Detector Control and Integration Software, Bruker Analytical X-

ray Systems Inc., Madison, Wisconsin, USA, 2006.[47] G.M. Sheldrick, Acta Crystallogr. A 64 (2008) 112.[48] J.E. Francis, L.A. Gorczyca, G.C. Mazzenga, H. Meckler, Tetrahedron Lett. 28

(1987) 5133.[49] L.F. Delboni, G. Oliva, E.E. Castellano, L.B. Zinner, S. Braun, Inorg. Chim. Acta

221 (1994) 169.[50] L. Pan, S. Kelly, X. Huang, J. Li, Chem. Commun. (2002) 2334.[51] K. Yoon, G. Parkin, J. Am. Chem. Soc. 113 (1991) 8414.[52] R. Santi, A.M. Romano, A. Sommazzi, M. Grande, C. Bianchini, G. Mantovani, J.

Mol. Catal. A: Chem. 229 (2005) 191.[53] A.D. Beitelman, G.M. Ferrence, Acta Crystallogr., Sect. E E63 (2007) m2520.[54] K. Yoon, G. Parkin, Polyhedron 14 (1995) 811.[55] T.W. Hambley, M.J. Lynch, E.S. Zvargulis, J. Chem. Soc., Dalton Trans. (1996)

4283.[56] S. Imai, K. Fujisawa, T. Kobayashi, N. Shirasawa, H. Fujii, T. Yoshimura, N.

Kitajima, Y. Moro-oka, Inorg. Chem. 37 (1998) 3066.[57] S. Kiani, J.R. Long, P. Stavropoulos, Inorg. Chim. Acta 263 (1997) 357.[58] C. Mealli, C.S. Arcus, J.L. Wilkinson, T.J. Marks, J.A. Ibers, J. Am. Chem. Soc. 98

(1976) 711.[59] N. Kitajima, K. Fujisawa, C. Fujimoto, Y. Moro-oka, S. Hashimoto, T. Kitagawa,

K. Toriumi, K. Tatsumi, A. Nakamura, J. Am. Chem. Soc. 114 (1992) 1277.[60] H.V.R. Dias, W. Jin, H.J. Kim, H.L. Lu, Inorg. Chem. 35 (1996) 2317.[61] K.H. Shaughnessy, Chem. Rev. 109 (2009) 643.[62] C.E. Housecroft, A.G. Sharpe, Inorganic Chemistry, 2nd ed., Pearson Prentice

Hall, Harlow, England, 2007 (Chapter 21).[63] R.C. Rosenberg, C.A. Root, R. Wang, M. Cerdonio, Proc. Natl. Acad. Sci. USA 70

(1973) 161.