A b s t r a c t : The reaction-coordinate for degenerate hydride-transfer between l,4-dihydropyridine and the pyridinium-ion was searched by MNDO calculations. A linear transition-state (TS) structure is found to be strongly ( 2 16 kcal/mole) preferred over a bent TS. In the former. rotation about the C-hvdride-C axis occurs unimDeded. thus creating a continuum of linear between exo and endo.In the past years, hydride-transfer processes, mediated by 1,4-dihydropyridines related to the NAD(P)H coenzymes have elicited much interest. Mechanistic shows that, for the majority of hydride-acceptors, these processes involve a single-step mechanism. In this context, insight into the factors governing the catalysis and stereochemistry of hydride-transfer under both enzymatic and non-enzymatic conditions, appears to be offered by elucidation of the transition-state (TS) geometry. Temperature dependence of the primary kinetic isotope effect (TDKIE6) was recently introduced5 9' as a tool to revea.1 the TS geometry of hydridetransfer under non-enzymatic conditions. Although the parameters obtained'q systems, both involving a positively charged hydride-acceptor, matched within experimental error, the conclusions drawn were not the same. Thus, while van Gerresheim et a 1 . 7 interpreted their data as indicating a linear "parallel-exo" TS, Powell and Bruice' inferred the occurrence of significant tunneling across a barrier corresponding to a bent "parallel-endo" 'l'S! Therefore it appeared desirable to obtain an impression of the preferred relative orientation of hydride-donor and positively charged substrate in the TS via quantum-chemical calculations on the semi-empirical SCF level. Related calculations on the cyclopropene/cyclopropenium system were recently carried out by Donkersloot and Buck', where a limited search of the configurational space revealed a linear hydride-transfer with a parallelexo TS.In the present approach the complete 1,4-dihydropyridine molecule was chosen as the hydride-donor since it represents the reactive part of NAD(P)H but for the CONH2 group. As extensive modifications of the latter, including substitution by e.g. COCH and CN, have been shown to leave the stereochemica? course of enzymatic hydride-transfer unchanged', its omission in the present calculations appears acceptable. As a model for the positively charged acceptor the pyridinium cation was chosen, which offered the additional advantage of symmetrical transition states. For the calculations, a local version of the MNDO was used. The first series of calculations were carried out with partial geometry optimization: both rings were given a fixed geometry, corresponding to that of pyridineU, except for the C(4)-H bonds. Table I under the heading part. These results suggest that the parallel-endo arrangement indeed enforces a bent TS but at the expense of a much higher barrier than the linear TS resulting from the parallel-exo arrangement. Next, it was studied whether the two transition states described could transform into each other. Thi...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.