Karl Weis

Evidence for a Trajectory of Hydrolytic Reactions brought about by [L3Zn−OH] Species

A proposal for a detailed geometrical pathway for the hydrolysis of substrates Y2PO−X and RCO−X, under the influence of zinc complexes or hydrolytic zinc enzymes, has been yielded by the combination of a kinetic study and a structure correlation analysis (see diagram). The essentials of this pathway are a four-center interaction between the Zn−OH and P−X or C−X units in the activation process and a Berry pseudorotation at zinc during the bond-breaking/bond-making process.

MODELLING TRANSITION STATE ANALOGUES AND ENZYME-INHIBITOR COMPLEXES OF ZINC-CONTAINING CLASS II ALDOLASES AND METALLOPROTEASES

Abstract The zinc complex Tp ∗ ZnOH ( 1: Tp ∗ = hydrotris -(3- cumyl ,5- methyl-pyrazolyl)borate ) which is a model of hydrolytic zinc enzymes was reacted with hydroxamic acids and hydroxyketones. Two hydroxamates Tp ∗ Zn-Hya ( 2 : Hya = acetohydroxamate , 3 : Hya = 2-hydroxamato-4-methylpentanoyl-alanyl-glycylamide ) and two ketoalcoholates Tp ∗ Zn-Kea ( 4 : Kea = hydroxyacetonate , 5 : Kea = cumoylacetonate ) were obtained. Crystal structure determinations of 2, 3 and 5 have revealed distorted ZnN 3 O 2 coordinations in each case. The immediate environment of the zinc ion in the hydroxamates closely resembles that in enzyme-(hydroxamate)inhibitor complexes of zinc-containing metalloproteases like collagenases and thermolysin or of class II aldolases like fuculose-1-phoshate aldolase. Like in the enzymes the hydroxamates and the ketoalcoholates can serve as transition state analogues of the enzyme-catalysed reactions.

Pyrazolylborate)zinc Organophosphate Complexes Resulting from Hydrolytic Cleavage of Phosphate Esters

Five different (pyrazolylborate)zinc hydroxide complexes Tp*Zn−OH (1) were used as hydrolytic reagents towards esters of various acids of phosphorus. Trimethyl phosphate and trimethyl phosphite could not be cleaved. Dimethyl and diphenyl phosphite yielded TptBu,MeZn−OPHO(OR) (2, 3). Triphenyl phosphate reacted slowly producing moderate yields of Tp*Zn−OPO(OPh)2 (4). Tris(p-nitrophenyl) phosphate was cleaved rapidly, forming Tp*Zn−OPO(OC6H4NO2)2 (5) and Tp*Zn−OC6H4NO2 (6). Alkylbis(p-nitrophenyl) phosphates showed intermediate reactivity, losing p-nitrophenolate upon hydrolysis and producing Tp*Zn−OPO(OR)(OC6H4NO2) (7, 8). When phosphorus acid diesters were employed, condensation between the Zn−OH and P−OH functions occurred. This proved to be the convenient way of preparing the organophosphate complexes Tp*Zn−OPO(Ph)2 (9), Tp*Zn−OPO(OPh)2 (4), and Tp*Zn−OPO(OC6H4NO2)2 (5). Six structure determinations showed the structural variability of the resulting complexes.

A new pyrazolylborate zinc hydroxide complex capable of cleaving esters, amides and phosphates

The L2·Zn–OH complex of the new ligand L2= hydrotris(3-p-isopropylphenyl-5-methylpyrazolyl)borate is a strong nucleophile which effects cleavage of activated esters, amides, non-activated phosphorus acid esters and diphosphates, thereby providing stoichiometric models of esterase, peptidase and phosphatase enzyme activity.