Solid-state conformations of nucleoside cyclic 3',5'-monophosphate derivatives. Effects of substituents on phosphorus on ring geometries and n/.sigma.* orbital interactions

Abstract

X-ray crystal structure data for seven nucleotide cyclic 3',5'-monophosphates, nine neutral cyclic nucleotide-based phosphate triesters, phosphonates, and phosphoramidates, and X-ray results for one new neutral, cyclic nucleotide-based phosphate triester were compared. Clearly evident is the pronounced flattening of the phosphate ring about phosphorus. This effect is greater for the neutral derivatives and assigned in part to an increased degree of stabilization arising from overlap of the p-like lone pair orbitals on 0(30 and 0(50 with the a* orbital of the axial substituent on phosphorus. Support for this interpretation is seen in shorter P-0(30 and P-0 (50 bonds noted for the neutral derivatives. The degree of flattening also is enhanced by steric repulsions involving axial substituents on phosphorus. Most of the structural features of these phosphate ring-based systems were successfully modeled by MNDO calculation on monocyclic analogues. Comparisons of these findings were made to those summarized earlier for the X-ray structures of the analogous monocyclic rings, for which ab initio calculations on systems that modeled those rings had been carried out. Similarities and differences between the cyclic nucleotide-based derivatives and the monocyclic systems were noted.