Coordination Sphere Of Zn Research Articles

2-Anilidomethylpyridine-Derived Three-Coordinate Zinc Hydride: The Journey Unveils Anilide Backbone's Reactive Nature.

Low-coordinate heteroleptic zinc hydrides are catalytically important but rare and synthetically challenging. We herein report three-coordinate monomeric zinc hydride on a 2-anilidomethylpyridine framework (NNL). The synthetic success comes through systematically screening a few different routes from different precursors. During the process, the ligand's anilide backbone interestingly appears to be more reactive than Zn's terminal site to electrophilic Lewis and Brønsted acids. The proligand NNLH reacts with [Zn{N(SiMe3)2}2] and ZnEt2 to give [(NNL)ZnA] (A = N(SiMe3)2 (1), Et(2)). Both are inert to PhSiH3 and H2 but react with HBpin only through the internal Zn-Nanilide bond to give the borylated ligand NNLBpin (3). The reactions of 1 and 2 with Ph3EOH (E = C, Si) afford a series of divergent compounds like [(NNLH)Zn(OSiPh3)2] (4), [Zn3(OSiPh3)4Et2] (5), and [EtZn(OCPh3)] (6). But in all cases, it is invariably the Zn-Nanilide bond protonated by the -OH with equal or higher preference than the terminal Zn-N or Zn-C bonds. A DFT analysis rationalizes the origin of such a reactivity pattern. Realizing that an acid-free route might be the key, reacting [(NNL)Li] with ZnBr2 gives [(NNL)Zn(μ-Br)]2 (7), which on successively treating with KOSiPh3 and PhSiH3 gives the desired [(NNL)ZnH] (8) as a three-coordinate monomer with a terminal Zn-H bond. Estimating the ligand steric in 8 shows the openness in Zn's coordination sphere, a desired criterion for efficient catalysis. This and a positive influence of the pyridyl sidearm is reflected in 8's superior activity in hydroborating PhC(O)Me by HBpin in comparison to Jones' two-coordinate anilido zinc hydride.

Analysis of the Role of Peripheral Ligands Coordinated to Zn(II) in Enhancing the Energy Barrier in Luminescent Linear Trinuclear Zn-Dy-Zn Single-Molecule Magnets.

Three new Dy complexes have been prepared according to a complex-as-ligand strategy. Structural determinations indicate that the central Dy ion is surrounded by two LZn units (L(2-) is the di-deprotonated form of the N2 O2 compartmental N,N'-2,2-dimethylpropylenedi(3-methoxysalicylideneiminato) Schiff base. The Dy ions are nonacoordinate to eight oxygen atoms from the two L ligands and to a water molecule. The Zn ions are pentacoordinate in all cases, linked to the N2 O2 atoms from L, and the apical position of the Zn coordination sphere is occupied by a water molecule or bromide or chloride ions. These resulting complexes, formulated (LZnX)-Dy-(LZnX), are tricationic with X=H2 O and monocationic with X=Br or Cl. They behave as field-free single-molecule magnets (SMMs) with effective energy barriers (Ueff ) for the reversal of the magnetization of 96.9(6) K with τ0 =2.4×10(-7) s, 146.8(5) K with τ0 =9.2×10(-8) s, and 146.1(10) K with τ0 =9.9×10(-8) s for compounds with ZnOH2 , ZnBr, and ZnCl motifs, respectively. The Cole-Cole plots exhibit semicircular shapes with α parameters in the range of 0.19 to 0.29, which suggests multiple relaxation processes. Under a dc applied magnetic field of 1000 Oe, the quantum tunneling of magnetization (QTM) is partly or fully suppressed and the energy barriers increase to Ueff =128.6(5) K and τ0 =1.8×10(-8) s for 1, Ueff =214.7 K and τ0 =9.8×10(-9) s for 2, and Ueff =202.4 K and τ0 =1.5×10(-8) s for 3. The two pairs of largely negatively charged phenoxido oxygen atoms with short DyO bonds are positioned at opposite sides of the Dy(3+) ion, which thus creates a strong crystal field that stabilizes the axial MJ =±15/2 doublet as the ground Kramers doublet. Although the compound with the ZnOH2 motifs possesses the larger negative charges on the phenolate oxygen atoms, as confirmed by using DFT calculations, it exhibits the larger distortions of the DyO9 coordination polyhedron from ideal geometries and a smaller Ueff value. Ab initio calculations support the easy-axis anisotropy of the ground Kramers doublet and predict zero-field SMM behavior through Orbach and TA-QTM relaxations via the first excited Kramers doublet, which leads to large energy barriers. In accordance with the experimental results, ab initio calculations have also shown that, compared with water, the peripheral halide ligands coordinated to the Zn(2+) ions increase the barrier height when the distortions of the DyO9 have a negative effect. All the complexes exhibit metal-centered luminescence after excitation into the UV π-π* absorption band of ligand L(2-) at λ=335 nm, which results in the appearance of the characteristic Dy(III) ((4) F9/2 →(6) HJ/2 ; J=15/2, 13/2) emission bands in the visible region.

Efficient Calculation of Enzyme Reaction Free Energy Profiles Using a Hybrid Differential Relaxation Algorithm: Application to Mycobacterial Zinc Hydrolases.

Determination of the free energy profile for an enzyme reaction mechanism is of primordial relevance, paving the way for our understanding of the enzyme's catalytic power at the molecular level. Although hybrid, mostly DFT-based, QM/MM methods have been extensively applied to this type of studies, achieving accurate and statistically converged results at a moderate computational cost is still an open challenge. Recently, we have shown that accurate results can be achieved in less computational time, combining Jarzynski's relationship with a hybrid differential relaxation algorithm (HyDRA), which allows partial relaxation of the solvent during the nonequilibrium steering of the reaction. In this work, we have applied this strategy to study two mycobacterial zinc hydrolases. Mycobacterium tuberculosis infections are still a worldwide problem and thus characterization and validation of new drug targets is an intense field of research. Among possible drug targets, recently two essential zinc hydrolases, MshB (Rv1170) and MA-amidase (Rv3717), have been proposed and structurally characterized. Although possible mechanisms have been proposed by analogy to the widely studied human Zn hydrolases, several key issues, particularly those related to Zn coordination sphere and its role in catalysis, remained unanswered. Our results show that mycobacterial Zn hydrolases share a basic two-step mechanism. First, the attacking water becomes deprotonated by the conserved base and establishes the new C-O bond leading to a tetrahedral intermediate. The intermediate requires moderate reorganization to allow for proton transfer to the amide N and C-N bond breaking to occur in the second step. Zn ion plays a key role in stabilizing the tetrahedral intermediate and balancing the negative charge of the substrate during hydroxide ion attack. Finally, comparative analysis of other Zn hydrolases points to a convergent mechanistic evolution.

Supramolecular structure of Cu(II) and Zn(II) complexes based on 2,2′:6′,2″-terpyridine, thermal and biological studies

Two supramolecular metal complexes [Cu(II)(terpy)(PCP)(NO3)](1) and [Zn(II)(terpy)(NO3)2](2) (terpy=2,2′:6′,2″-terpyridine) (PCP = Pentacyanopropenide) were synthesized and structurally characterized by Single-crystal X-ray diffraction. Single-crystal X-ray diffraction revealed that the PCP ligand coordinated to Cu(II) ion through one CN group, and it was absent from the coordination sphere of Zn(II) complex. In complexes (1) and (2), 1D chain was formed through C1–H1···O1 and C4–H4···O2 hydrogen-bonding interactions, respectively. The crystal structure was further stabilized by π–π stacking interactions. The thermal stabilities of these compounds were investigated. Furthermore, antimicrobial activities of these compounds were investigated against eight types of bacteria. The copper complex exhibited a significant activity against three types of bacteria with minimal inhibitory concentrations (MICs) under one microgram per milliliter.

The impact of zinc on insulin fibrillation

Protein and peptide amyloid fibrillation is an increasingly significant field of research due to the growing prevalence and recognition of amyloid-related human diseases and in relation to therapeutic applications of peptide drugs where it constitutes a challenge during production and transportation. Insulin fibrillation represents a good model system for fibrillation studies and numerous pathways of insulin fibrillation have been suggested [1]. In general, partially unfolded insulin monomers (or dimers) are believed to be a vital prerequisite for prefibrillar association and eventually fibril formation (reviewed by Groenning in [1]). As fibrillation is commonly found to occur from the biologically active, monomeric form of insulin, zinc is considered to impede insulin fibril formation through stabilization of the physiological predominant hexameric forms. The question arises whether the assigned monomeric pathway at least to some degree could be a premise generated from the usual experimental procedure of inducing fibril formation; experiments that are conducted at acidic conditions with protonated histidine residues that cannot coordinate the Zn(II) ions, to induce the monomeric form believed to be the prerequisite of insulin fibrillation? However, in a more recent study [2], it was suggested that Zn(II) ions in contrast also inhibit fibrillation through differential stabilization of the insulin monomer. In the present work, we have investigated the presence and influence of zinc at well-defined stoichiometric levels at physiological pH, as well as the inner coordination sphere of Zn(II) during insulin fibril formation, using X-ray absorption spectroscopy (XAS). In addition, the results were validated with fiber diffraction studies, small-angle X-ray studies and ThT fluorescence studies.

Preparation, X-Ray Structures, and Cytotoxic Property of Mononuclear Schiff Base Zinc Complexes [Zn(SalPr)2] and [ZnI2(SalPt)2

Schiff bases obtained from 5-chlorosalicylaldehyde with cyclopropylamine, and 4-methoxysalicylaldehyde with cyclopentylamine, were used as ligands for Zn(II) resulting in two mononuclear zinc complexes, [Zn(SalPr)2] and [ZnI2(SalPt)2], where SalPr is 4-chloro-2-(cyclopropyliminomethyl)phenolate and SalPt is 2-(cyclopentyliminiummethyl)-5-methoxyphenolate. The detailed structures of the complexes were determined by single crystal X-ray crystallography. Coordination sphere of Zn(II) atoms in both complexes are slightly distorted tetrahedron. The cytotoxic property of the complexes was evaluated.

Ultrahigh-resolution crystal structures of Z-DNA in complex with Mn2+and Zn2+ions

X-ray crystal structures of the spermine(4+) form of the Z-DNA duplex with the self-complementary d(CG)3 sequence in complexes with Mn(2+) and Zn(2+) cations have been determined at the ultrahigh resolutions of 0.75 and 0.85 Å, respectively. Stereochemical restraints were only used for the sperminium cation (in both structures) and for nucleotides with dual conformation in the Zn(2+) complex. The Mn(2+) and Zn(2+) cations at the major site, designated M(2+)(1), bind at the N7 position of G6 by direct coordination. The coordination geometry of this site was octahedral, with complete hydration shells. An additional Zn(2+)(2) cation was bis-coordinated in a tetrahedral fashion by the N7 atoms of G10 and G12 from a symmetry-related molecule. The coordination distances of Zn(2+)(1) and Zn(2+)(2) to the O6 atom of the guanine residues were 3.613 (6) and 3.258 (5) Å, respectively. Moreover, a chloride ion was also identified in the coordination sphere of Zn(2+)(2). Alternate conformations were observed in the Z-DNA-Zn(2+) structure not only at internucleotide linkages but also at the terminal C3'-OH group of G12. The conformation of the sperminium chain in the Z-DNA-Mn(2+) complex is similar to the spermine(4+) conformation in analogous Z-DNA-Mg(2+) structures. In the Z-DNA-Zn(2+) complex the sperminium cation is disordered and partially invisible in electron-density maps. In the Z-DNA-Zn(2+) complex the sperminium cation only interacts with the phosphate groups of the Z-DNA molecules, while in the Z-DNA-Mn(2+) structure it forms hydrogen bonds to both the phosphate groups and DNA bases.

Analysis of zinc‐ligand bond lengths in metalloproteins: Trends and patterns

Zinc is one of the biologically most abundant and important metal elements, present in a plethora of enzymes from a broad array of species of all phyla. In this study we report a thorough analysis of the geometrical properties of Zinc coordination spheres performed on a dataset of 994 high quality protein crystal structures from the Protein Data Bank, and complemented with Quantum mechanical calculations at the DFT level of theory (B3LYP/SDD) on mononuclear model systems. The results allowed us to draw interesting conclusions on the structural characteristics of Zn centres and to evaluate the importance of such effects as the resolution of X-ray crystallographic structures, the enzyme class in which the Zn centre is included, and the identity of the ligands at the Zn coordination sphere. Altogether, the set of results obtained provides useful data for the enhancement of the atomic models normally applied to the theoretical and computational study of zinc enzymes at the quantum mechanical level (in particular enzymatic mechanisms), and for the development of molecular mechanical parameters for the treatment of zinc coordination spheres with molecular mechanics or molecular dynamics in studies with the full enzyme.

The Carboxylate Shift in Zinc Enzymes: A Computational Study

Zinc is the second most abundant transition element in biology and the only metal known to be represented in enzymes from each one of the six classes established by the International Union of Biochemistry. The flexible coordination geometry, the fast ligand exchange, the lack of redox activity, and its role as Lewis acid are just some of the features that make zinc an invaluable element in biological catalysis. In this study, we have analyzed the importance in mononuclear Zn enzymes of an interesting mechanistic phenomenon known as carboxylate shift, which is characterized by a change in the coordination mode of a carboxylate group (mono to bidentate or vice versa) with both ligand entrance or exit from the metal coordination sphere. Using B3LYP calculations, we were able to unveil in detail patterns relating the intrinsic characteristics of a given Zn coordination sphere with the existence or not of a carboxylate-shift mechanism and the additional energy stabilization arising from it. In particular, a specific Zn coordination sphere containing a carboxylate ligand (Asp or Glu), a cysteine, and a histidine has been shown to have the most favorable combination of amino acid residues that ensures a fast ligand exchange.

Syntheses and crystal structures of two mixed-ligand dimeric zinc complexes containing a dithiol ligand and an open chain crown ether ligand with terminal quinolyl groups

Two mixed-ligand zinc complexes Zn(L)(H 2O)(mnt) ( 1) and Zn(L)(H 2O)(i-mnt) ( 2) (where L=2,6-bis(8′-quinoylyloxymethyl)pyridine, mnt =1,2-dicyanoethylene-1,2-ditholate and i-mnt =1,1-dicyanoethylene-2,2-ditholate) have been synthesized and characterized by elemental analysis, FT-IR spectra, and single-crystal X-ray diffraction. Complexes 1 and 2 both crystallize in the monoclinic system, space group C2/ c and each displays a distorted trigonal bipyramidal around zinc atom. The coordination sphere of Zn is NO 2S 2 type, where the dithiol ligand (mnt or i-mnt) and one terminal quinolyl group of L act as the chelate S, S and N, O donor sets, respectively, besides the coordination water molecules. Furthermore, there are intramolecular H-bonds occurred between the coordination water molecule and the N2, N3 atoms of the L and the molecules of 1 and 2 both form the dimers through the intermolecular π–π stacking interactions.

Interactions of Transition Metal Ions with His‐Containing Peptide Models of Histone H2A

AbstractFor Abstract see ChemInform Abstract in Full Text.

Five-coordinate zinc(II) complexes with optically active Schiff bases derived from (1 R,2 R)-(−)cyclohexanediamine: X-ray structure and CP MAS NMR characterization of [cyclohexylenebis(5-chlorosalicylideneiminato)zinc(II)pyridine] and [cyclohexylenebis(5-bromosalicylideneiminato)zinc(II)pyridine

Schiff bases obtained from (1 R,2 R)-(−)-cyclohexanediamine and 5-chloro- ( 1) or 5-bromosalicylaldehyde ( 2) are used as ligands for Zn(II) resulting in [(1 R,2 R)-cyclohexylenebis(5-chlorosalicylideneiminato)]zinc(II) ( 1a) and (1 R,2 R)-[cyclohexylenebis-(5-bromosalicylideneiminato)]zinc(II) ( 2a). In the presence of pyridine, 1a and 2a turned out into (1 R,2 R)-[cyclohexylenebis(5-chlorosalicylideneiminato)pyridine]zinc(II) ( 1b) and (1 R,2 R)-[cyclohexylenebis(5-bromosalicylideneiminato)pyridine]zinc(II) ( 2b). Coordination sphere of Zn(II) atoms in both pyridine adducts is a slightly distorted square pyramid, with N 2O 2 chromophore units and axially bonded pyridine as it is evident from single crystal X-ray analyzes of 1b and 2b. The asymmetric unit of 1b and 2b contains two molecules of complexes. The observed distances of Zn–O in both molecules indicate the rigidity of the tetradentate ligand as a main factor influencing the geometry of coordination sphere. Obtained complexes were characterized by 1H NMR in solution and 13C CP MAS NMR. NOE differential experiments revealed significant steric interactions between C(6)–H in the phenyl ring, cyclohexyl C(1)–H and imine hydrogen. Significant coordination shifts of carbons in the closest proximity to the coordination center were noted as well.

Interactions of transition metal ions with His-containing peptide models of histone H2A

The coordination properties of Ni(II), Cu(II) and Zn(II) ions towards the terminally blocked (CH 3CONH– and –CONH 2) hexapeptides –TESHHK–, –TASHHK–, –TEAHHK–, –TESAHK– and –TESHAK–, which are all models of the C-terminal “tail” (–ESHH–) of histone H2A, were studied by potentiometric and several spectroscopic techniques (UV/Vis, CD, NMR, EPR). The peptides were chosen in such a way as to compare the effect of Glu, Ser and His residues on the stability, the coordination and hydrolytic abilities of the complexes formed. It was found that all peptides bind to the metal ions initially through one or two imidazole nitrogens in weakly acidic and neutral solutions forming slightly distorted octahedral complexes. At higher pH values, a series of square-planar complexes are formed with Ni(II), which binds simultaneously through an imidazole and three amide nitrogens in an equatorial plane. This proposed conformation includes the participation of only one imidazole nitrogen, in the case of all peptides, in the coordination sphere of Ni(II) ions. Additionally, all peptides coordinate Cu(II) efficiently. At higher pH values, Cu(II) ions coordinate equatorially with the imidazole nitrogen of His-5 or His-4 and three amido nitrogens of the peptides –TESAHK– and –TESHAK–, while the second histidine residue of the peptides –TESHHK–, –TASHHK– and –TEAHHK– is additionally bound in the apical position. In contrast, the combination of potentiometric titrations and one- and two-dimensional 1H-NMR suggested no amide coordination in the coordination sphere of Zn(II) ions, over a wide range of pH. In basic solutions, the peptides –TASHHK– and –TESAHK– were hydrolyzed in a Ni(II)-assisted fashion, while no hydrolytic processes were noticed in peptides –TEAHHK– and –TESHAK– where the Ser or His-5 residues are replaced with the Ala residue. Moreover, CuH −1L complex with –TESHHK– reacts with H 2O 2 and the resulting reactive oxygen intermediate efficiently oxidizes 2′-deoxyguanosine.

Interactions of Zn(II) Ions with Three His-Containing Peptide Models of Histone H2A

The interactions of Zn(ll) ions with the blocked hexapeptide models -TESHHK-, -TASHHK- and -TEAHHK- of the -ESHH- motif of the C-terminal of historic H2A were studied by using potentiometric and IH-NMR techniques. The first step of these studies was to compare the pKa values of the two His residues inside each hexapeptide calculated by potentiometric or H-NMR titrations. Hereafter, the potentiometric titrations in the pH range 5 11 suggest the formation of several monomeric Zn(ll) complexes. It was found that all hexapeptides bind to Zn(ll) ions initially through both imidazole nitrogens in weakly acidic and neutral solutions forming slightly distorted octahedral complexes. At higher pH values, the combination of potentiometric titrations and one and two dimensional NMR suggested no amide coordination in the coordination sphere of Zn(II) ions. Obviously, these studies support that the -ESHH- sequence of histone H2A is a potential binding site for Zn(II) ions similarly with the Cu(II) and Ni(ll) ions, presented in previous papers.

Interaction of Alcohol Dehydrogenase with tert-Butylhydroperoxide: Stimulation of the Horse Liver and Inhibition of the Yeast Enzymes

Preincubation of horse liver alcohol dehydrogenase (HLADH) with the oxidative agent, tert-butyl hydroperoxide (tBOOH) results in a twofold stimulation of the ethanol dehydrogenase activity of this enzyme. This stimulation was dependent on tBOOH concentration up to 100 mM; above this concentration tBOOH did not further stimulate ethanol oxidation by HLADH. Active-site-directed reagents and classical ADH binary complexes were used to probe the possible mechanism of this activating effect. The rate and extent of stimulation by tBOOH is strongly reduced by binary complexes with NAD+ or NADH, whose pyrophosphate groups bind to Arg-47 and Arg-369. In contrast stimulation by tBOOH was not prevented by AMP or the sulfhydryl reagents dithiothreitol and glutathione, suggesting, respectively, a lack of role for Lys-228 and sulfhydryl group oxidation in the stimulation by tBOOH. In contrast to the liver enzyme, treatment of yeast ADH (YADH) with tBOOH irreversibly inhibited its ethanol dehydrogenase activity. Inhibition of YADH by tBOOH approximated first-order rate kinetics with respect to enzyme at fixed concentrations of tBOOH between 0.5 to 300 mM. Four –SH groups per molecule of YADH were modified by tBOOH, whereas only two –SH groups were modified in HLADH. The stimulation of HLADH by tBOOH is suggested to be due to destabilization of the catalytic Zn-coordination sphere and amino acids associated with coenzyme binding in the active site, while inactivation of YADH appears to be associated with –SH group oxidation by the peroxide.

Structure of pyrophosphate 2ZnO · P 2O 5–2Na 2O · P 2O 5 glasses according to molecular dynamics simulation

Short-range order structures of 2ZnO · P 2O 5–2Na 2O · P 2O 5 glasses were investigated by molecular dynamics simulations. Distributions of structural units including orthophosphate, pyrophosphate and longer metaphosphate chains were found in the anionic phosphate structure. In terms of the Q-site model, the predominant species are Q 1 groups as expected from the used stoichiometry. Sodium plays a modifying role in all glasses studies. The structural role of Zn ion is more complex. Decreasing zinc oxide content leads to change of its properties from modifying cation in vitreous zinc pyrophosphate to network forming one in ZnO · Na 2O · P 2O 5 glass. There is a correlation in the location of the Zn ion at relative long distances, about 0.6 nm, in all samples and their liquids. In principle, the existence of the second coordination sphere of Zn may be detected experimentally.

Kinetic and structural characterization of spinach carbonic anhydrase.

We have carried out kinetics studies of spinach carbonic anhydrase (CA) using stopped-flow spectrophotometry at steady state and 13C-NMR exchange at chemical equilibrium. We found that the rate of CO2<-->HCO3- exchange catalyzed by spinach CA at pH 7.0 to be 3-5 times faster than the maximal kcat for either CO2 hydration or HCO3- dehydration at steady state, suggesting a rate-determining H+ transfer step in the catalytic mechanism. Correspondingly, we measured a pH-independent solvent deuterium isotope effect on kcat of approximately 2.0, and found that the rate of catalysis was significantly decreased at external buffer concentrations below 5 mM. Our results are consistent with a zinc-hydroxide mechanism of action with for spinach CA, similar to that of animal carbonic anhydrases. We have also collected X-ray absorption spectra of spinach CA. Analysis of the extended fine structure (EXAFS) suggests that the coordination sphere of Zn in spinach CA must have one or more sulfur ligands, in contrast to animal CAs which have only nitrogen and oxygen ligands. The models which best fit the data have average Zn-N(O) distances of 1.99-2.06 A, average Zn-S distances of 2.31--2.32 A, and a total coordination number of 4-6. We conclude that animal and spinach CAs are convergently evolved enzymes which are structurally quite different, but functionally equivalent.

A model for catalytically active zinc(II) ion in liver alcohol dehydrogenase: a novel "hydride transfer" reaction catalyzed by zinc(II)-macrocyclic polyamine complexes

The role of Zn ion at the active center of liver alcohol dehydrogenase has been well-defined for the first time by the comparative studies of Zn( 12)aneN3, 1 ((12)aneN3 = 1,5,9-triazacyclododecane, L,), Zn( 12)aneN4, 2 (( 12)aneN4 = 1,4,7,10-tetraazacyclododecane, L2), Zn( 14)aneN4, 3 (( 14)aneN4 = 1,4,8,1 I-tetraazacyclotetradecane, LJ, and free Zn salts, 4. Variations in Zn acidity and coordination environment in these complexes result in varying degrees of catalytic activity in the reduction of p-nitrobenzaldehyde (9) and an NAD' model compound (18) with alcohols as the sources (e.g., 2-PrOH) to p-nitrobenzyl alcohol (10) and the corresponding NADH model compounds (19 and 20), respectively. Among Zn species tested, the Zn complex of macrocyclic triamine ( 1 2)aneN3, 5 (L,-Zn11-OH)3.(TfO)3.TfOH (TfO = CF3S03-), was by far the most effective catalyst: 10 was obtained from 9 in 7820% yield (based on the concentration of Zn) in the presence of 5 (0.8 mol %) in refluxing 2-PrOH for 24 h. The Zn complex 5, also promotes the from 2-PrOH to an NAD' model compound, N-benzylnicotinamide chloride (18), to yield the 1,4-adduct, N-benzyl-l,4-dihydronicotinamide (19), almost exclusively. It is concluded, from the comparison of 5 with other Zn complexes of ( 12)aneN4 and ( 14)aneN4, that the most acidic and coordinatively least saturated Zn in LI catalytically generates zinc( 11)-alkoxide complex to facilitate the hydride transfer to the hydride acceptor on the Zn coordination sphere. The present study provides the first chemical model illustrating the significance of the Zn acidity and the steric requirement around Zn coordination sphere in the hydride transfer reaction (from alcohol) catalyzed by Zn%ontaining alcohol dehydrogenases (ADH).

X-ray absorption fine structure study of the active site of zinc and cobalt carboxypeptidase A in their solution and crystalline forms

A comparative study on the metal environment of Zn(II)-carboxypeptidase A (ZnCPD) and Co(II)-carboxypeptidase A (CoCPD) in their solution and crystalline forms using the X-ray absorption fine structure (XAFS) technique has been conducted. The first coordination sphere of Zn for ZnCPD in its solution state is found to consist of two distributions of atoms, with four atoms (N or O) located at an average distance of 2.03 +/- 0.01 A and one atom (N or O) located at 2.57 +/- 0.04 A. The four-atom distribution remains the same for ZnCPD in its crystalline state, but the fifth atom is found at 2.36 +/- 0.04 A. Examination of the higher coordination shell, between 2.7 and 4.2 A, reveals the presence of two imidazoles. Combined with X-ray crystallographic results, a structural model is proposed. The four atoms at an average distance of 2.03 A are assigned to the two delta 1 nitrogens of His-69 and His-196, one epsilon 1 oxygen of Glu-72, and the oxygen of a coordinated water molecule. The atom at 2.57 A for ZnCPD in solution is assigned to the epsilon 2 oxygen of Glu-72. The results for CoCPD in solution are similar with the four atoms at an average distance of 2.08 +/- 0.01 A and one atom at 2.50 +/- 0.04 A, which moves to 2.34 +/- 0.04 A in the crystalline enzyme. The intensity of the 3d "pip" peak for CoCPD is consistent with a distorted tetragonal metal geometry for the solution form of the enzyme which is converted to a more pentacoordinated metal site for the crystalline enzyme. The first shell distribution of crystalline CoCPD is quite disordered, which may be largely due to the disorder of His-69 and His-196 as indicated by higher shell analysis. Thus, the XAFS studies show that the metal coordination spheres in the zinc and cobalt enzymes are quite similar in the solution state but differ from their crystalline counterparts. The XAFS studies provide the necessary background for measurement of substrate- and inhibitor-promoted structural changes in the metal coordination sphere of the zinc and other metal-substituted carboxypeptidases in the solution state.

Proton transfer in the water dimer catalyzed by doubly charged cations (Zn+2, Be+2, and Mg+2)

The proton transfer process in the water dimer complex catalyzed by three divalent metal ions has been studied throughab initio methods using different basis sets. Calculations with a dipositive charge placed at different distances from one of the oxygens of the water dimer have been also performed. A catalysis found in this process owing to both electrostatic and charge-transfer effects. Morokuma analyses show that the electrostatic effect is the most important for this proton transfer. The effect of the ligands in the coordination sphere of Zn+2 is also discussed by studying the same proton transfer process in a Zn+2 complex with three NH3 ligands.