Syntheses of macrocyclic enzyme models. Part 5. Preparation and metal-co-ordination behaviour of [20]paracyclophane bearing 1,4-dihydronicotinamide and pyridine-2-carboxylic acid moieties as an alcohol dehydrogenase model

Abstract

A [20]paracyclophane (PCP) bearing 1,4-dihydronicotinamide (HNA) on the benzene ring and pyridine-2-carboxylic acid (Py) as a metal-binding ligand on C-10 of the macrocycle via an amide linkage, HNA–PCP–Py, has been prepared as a model for the NAD-dependent alcohol dehydrogenase. Its co-ordination behaviour with zinc(II) ion in dichloromethane–methanol and dichloromethane–propan-2-ol (100 : 1 v/v) has been investigated and compared with those of PCP–HNA and PCP–Py. PCP–Py. PCP–Py forms zinc complexes having 2 : 1 and 1 : 1 (PCP–Py to Zn^II) stoicheiometry, the 2 : 1 complex predominating over the 1 : 1 complex in stability. PCP–HNA also forms a relatively stable 1 : 1 complex with zinc ion (PCP–HNA–Zn^II), in which the dihydronicotinamide moiety provides a metal-binding site, with a stability constant an order of magnitude larger than the overall stability constant for PCP–Py–Zn^II. The major zinc-bound species of HNA–PCP–Py is a 1 : 1 complex (PC[graphic omitted]Zn^II), in which both Py and HNA moieties are simultaneously co-ordinated to the same zinc ion. Detailed analysis of the co-ordination equilibria indicates that the 2 : 1 complex (HNA–PCP–Py–Zn^II–Py–PCP–HNA), in which HNA is free from metal co-ordination, provides only a minor contribution to the overall zinc co-ordination scheme.