Zn−O₂H₃−Zn:  a Coordination Mode of the Hydrolytic Zinc−Aqua Function and a Possible Structural Motif for Oligozinc Enzymes

Abstract

Reactions of the pyrazolylborates KTp‘ with Zn(ClO4)2 and KOH in a 2:2:1 ratio yield the complexes [Tp‘2Zn2O2H3]ClO4 (1) for Tp‘ = hydrotris(3-R-5-methylpyrazolyl)borate with R = p-isopropylphenyl (a), 3-pyridyl (b), and 3-(6-methyl)pyridyl (c). Their structure determinations have revealed a Zn-OH-H···OH-Zn array (i.e., a bridging H3O2 - ligand) in the dinuclear complex cations. The zinc ions in complex 1a are in a distorted tetrahedral ZnN3O environment, and those in 1b and 1c are in a distorted trigonal bipyramidal ZnN4O environment due to additional coordination of one pyridyl nitrogen from the opposing Tp‘ ligand. In 1b, one Zn-OH function is involved in a hydrogen bridge to a cocrystallized methanol molecule. The complexes represent a mode of stabilization for the zinc−aqua function in the cationic Tp‘Zn-OH2 species, and they are intermediates in the formation of the stable Tp‘Zn-OH complexes. It is suggested that the Zn-O2H3-Zn unit is present as a structural and possibly functional motif in oligozinc enzymes like phospholipase C or P1 nuclease.

Biomimetic Hydrolysis of Penicillin G Catalyzed by Dinuclear Zinc(II) Complexes: Structure–Activity Correlations in β‐Lactamase Model Systems

“…[36][37][38]41] It is interesting to note that the different situations of a Zn-O(H)-Zn bridge in 1, 3 versus a Zn-O 2 H 3 -Zn bridge in 2, 4 closely resemble the two active-site model configurations A ("tightly bridged") and B ("loose" or "nonbridged") described above, with Zn···Zn separations of~3.5 and~4.4 , respectively. The Zn-O 2 H 3 -Zn unit has previously been proposed as a structural and possibly functional motif in oligozinc enzymes, [35,42] and most recently this has been supported by DFT calculations on the bovine lens leucine aminopeptidase (blLAP) active site. [43] Since adducts of complexes 1-4 with penicillin G (or its hydrolytically cleaved form) could not be obtained as single crystals, for binding studies we also used simple b-lactams such as N-benzylazetidinone (nba) and oxazetidinylacetate (oaa), which contain essential structural elements of the common antibiotics (b-lactam amide or b-lactam amide and carboxylate, respectively).…”

The Catalytic Mechanisms of Binuclear Metallohydrolases

“…252,270 The pK a values reported for Zn(II)-bound water molecules in a range of model complexes depend strongly on the coordination environment and range from 7.3 to 10.8. [290][291][292][293][294][295][296] Since E. coli 5′-NT is an efficient catalyst even at pH 6, it seems likely that the pK a of the terminal water molecule is lowered through hydrogen bonding interactions with His117 ( Figure 22A). The pH dependence of kinetic parameters for 5′-NT-catalyzed reactions has not yet been analyzed in detail, but based on pH optima ranging from 5.5 to 9 for different enzymes, it appears that in some 5′-NTs the likely candidate for the role of a nucleophile is the bridging water ligand, which is expected to have a lower pK a value.…”

Effect of Zn⋅⋅⋅Zn Separation on the Hydrolytic Activity of Model Dizinc Phosphodiesterases

“…The latter bimetallic arrangement with a bridging O 2 H 3 À group can be described as a combination of a Zn-OH 2 function with a Zn-OH function, and hence as a hydrated form of an active terminal Zn-OH. Such an O 2 H 3 À moiety has been observed both as an intermolecular and as an intramolecular bridge in zinc model complexes [21][22][23] and has been suggested as a new structural and possibly also functional motif in oligozinc enzyme chemistry. [21] Its functional relevance is also supported by recent DFT calculations concerning the mode of action of dizinc b-lactamase from Bacteroides fragilis [24] and of bovine lens leucine aminopeptidase.…”