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Zinc(II) Complexation Behaviour of Sulfonamide‐Based Enzyme Inhibitors
Author(s) -
Chaves Sílvia,
Marques Sérgio M.,
Cachudo Anabela,
Esteves M. Alexandra,
Santos M. Amélia
Publication year - 2006
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.200600443
Subject(s) - chemistry , sulfonamide , zinc , hydroxamic acid , carbonic anhydrase , enzyme , infrared spectroscopy , active site , metal , chelation , aqueous solution , stereochemistry , combinatorial chemistry , medicinal chemistry , inorganic chemistry , organic chemistry
Sulfonamide derivatives containing extrafunctional groups, such as hydroxamic acids, hydroxypyrimidinones and carboxylic acids, have been recently identified as inhibitors towards several zinc‐containing enzymes, such as the matrix metalloproteinases (MMPs) and/or carbonic anhydrases (CAs). Since these inhibitors are supposed to bind the zinc ion at the active site, it was decided to study the zinc(II) complexation with a set of representative compounds in order to identify the most probable coordination modes and to find eventual relationships with the inhibitory properties. These studies were performed in aqueous solution, by potentiometry and 1 H NMR spectroscopy, and in the solid phase, by infrared spectroscopy. The solution equilibrium studies indicate that these compounds present similar affinity for zinc (pZn ≈ 6). Under stoichiometric conditions, the formation of 1:1 metal complex species involves a preferential ( O , O ) coordination via the hydroxamic or hydroxypyrimidinone moieties, while the coordination via the sulfonamide groups could mainly be achieved under zinc excess conditions.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)