Nicotinamide zinc complexes

Nickel-tin alloys electroplating, 6,14 Nicotinamide zinc complexes, 5,952 hydride-transfer reactions, 5, 954 Nicotinic acid... 

Figure 15-5 Structure of the complex of horse liver alcohol dehydrogenase with NAD+ and the slow substrate p-bromobenzyl alcohol. The zinc atom and the nicotinamide ring of the bound NAD+ are shaded. Adjacent to them is the bound substrate. Courtesy of Bryce Plapp. Based on Ramaswamy et al.53...

The involvement of zinc in nicotinamide-based hydride-transfer reactions has led to numerous studies of Group IIB complexes of pyridine carboxylic acid derivatives. Cadmium complexes of 2-pyridinecarboxylic acid, 5 3-pyridinecarboxylic add497 and 3-pyridinecarboxamide498 have been reported. The crystal structure of [Cd(HC02)2L2(H20)2] (L = 3-pyridinecarboxamide) has also been described the metal is in an octahedral environment in which the amide acts as a monodentate N donor.498... 

A similarity between the location of zinc(n) in yeast alcohol dehydrogenase (YADH) and that of the metal in LADH has been established.240 NADH and substrate proton relaxation rates using the paramagnetic iodoacetamide analogue complex of YADH show the coenzyme nicotinamide moiety to be situated ca. 7 A from the zinc ion. This is virtually identical with the position of the metal in LADH determined by X-ray crystallography.241 The substrate resides between the NADH and the metal ion, i.e. it is co-ordinated to the zinc. 

One group of NADH oxidants, which does not fit the proposed reaction scheme in Fig. 2.4 are the metal complexes. Examples of this type include nickel hexacyanoferrate deposited on porous nickel electrodes [29], gold electrodes modified with cobalt hexacyanoferrate films [30] and adsorbed l,10-phenanthroline-5,6-dione complexes of ruthenium and osmium [31]. It is unclear how these systems work and no mechanism has been proposed to date. It may be worth noting that dihydronicotinamide groups have been shown to reduce aldehydes in a non-enzymatic reaction when the reaction is catalysed by zinc, a metal ion [15]. In a reaction between 1,10-phenanthroline-2-carboxaldehyde and N-propyl-l,4-dihydronicotinamide, no reaction was seen in the absence of zinc but when added to the system, the aldehyde was reduced and the nicotinamide was oxidised. This implies that either coordination to, or close proximity of, the metal ion activates... 

The Z isomer of the model substrate 4-tra s- N,]V -dimethylamino)cinnamaldoxime (Z-DMOX) forms a ternary complex with NAD and LADH. The Co", Ni, Cu and Cd enzymes (with the metal substituted for the catalytic zinc) and the apoenzyme also form ternary complexes with Z-DMOX. The affinity of the apoenzyme-NAD complex for Z-DMOX is much lower and the rate of Z-DMOX dissociation from the apoenzyme complex was 10 -fold greater than the rates found for the metal-substituted enzymes. Complex formation results in a red shift (43 to 83.5 nm) in the DMOX UV-visible spectrum, due, it is suggested, to bonding of the oxime nitrogen to a strong electrophilic centre, either the Zn or the nicotinamide ring of NAD, a view that is compatible with the known structural features of the LADH/NADH/MejSO complex. The high affinities and slow rates of dissociation of the metal-substituted enzyme complexes are attributed to the coordination of Z-DMOX to the active site metal. ... 

It could be shown, moreover, (Vallee and Neurath, 1955) that five times recrystallized carboxypeptidase was completely inhibited by metal chelating agents, such as 8-OHQ-5SA and 1-10 phenthroline at concentrations of 10 W,Q ,Q Dat concentrations of 10" Af, and some 30% byEDTA at 10 M. These are all known to form complexes with zinc in simple systems. In these experiments, the buffered enzyme solutions were incubated with the chelating agent at pH 7.5, 4°C., for 1 hour prior to the addition of the substrate. Inhibition did not occur when these chelating agents were first incubated with an equimolar amount of zinc, cupric, or ferrous ions. Sodium diethyldithiocarbamate, zincon, sulfanilamide, and diamox, the latter two employed because of their effect on carbonic anhydrase, had little, if any, effect on carboxypeptidase activity. DPN, nicotinamide, and A-methylnicotinamide, examined because of their effect on the ADH sys-... 

The binding of 1,10-phenanthroline has been studied by X-ray methods (112) in order to correlate a large number of inhibitor studies in solution with the structure (Section II,H,l,b). This chelating agent binds to the zinc atom in the active site displacing the water molecule. The metal is, thus, five coordinated in the complex. The aromatic ring system of the inhibitor is positioned in the active site pocket partly overlapping the assumed nicotinamide position. 

Fig. 2. Reasonable structural explanation for the stereospecilicity of hydrogen transfer catalyzed by horse liver alcohol dehydrogenase. The binary complexes were obtained by building ethanol into the X-ray structure of the holoenzyme, on the basis of the assumption that the ethanolic oxygen is directly coordinated to the active site zinc ion. (A) When the pro-(R) proton of ethanol is directed at C-4 of the nicotinamide ring, the methyl function is favorably positioned in the active site (B) when the pro-(S) proton is directed at C-4, the methyl function interacts stcrically with Phe-93. (From Ref. 30), with permission.]...

The high resolution X-ray structural studies of the native enzyme, the enzyme-ADPR binary complex, and the enzyme-o-phenanthroline binary complex (47) have revealed that the active site zinc ion is located some 20 A below the surface of the protein at the point of convergence of two deep clefts (see the schematic representation in Fig. 6). One of these clefts has been identified as the coenzyme binding cleft (47). This cleft extends from the surface of the subunit to the zinc ion. If a model of NADH is fit to the coordinates of the ADPR binding site, then the nicotinamide ring can be oriented in such a way that it fits into a pocket adjacent to the zinc ion (47). The second deep cleft, or channel, also extends from the surface of the subunit down to the zinc ion. The inner surface of this cleft is made up of nonpolar amino acid residues contributed by both subunits. 

New complex compounds of general formula Zn(4-ClC6H3-2-(0H)C00 2 L2 nH20 (where L=thiourea (tu), nicotinamide (nam), caffeine (caf), n=2,3), were prepared and characterized by Gyoryova and coworkers [230], vfho studied their thermal properties by TG/DTG and DTA methods. Thermal decomposition of the hydrated compounds starts with the release of water molecules. During the thermal decomposition of the anhydrous compounds, the release of organic ligands take place, followed by the decomposition of the salicylate anion. Zinc oxide was the final solid product of the thermal decomposition performed up to 650 C. TG, powder XRD, IR spectra and chemical analysis were used for the determination of the products of the thermal decomposition. 

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