The two-state N/S model of Altona and Sundaralingam is a dominant paradigm in the conformational analysis nucleosides and nucleotides. It is well-demonstrated that most nucleos(t)ides exist in solution as a mixture of 'north' (C2'-exo/C3'-endo) and 'south' (C2'-endo/C3'-exo) conformers in solution; the precise nature of the N/S conformations and their relative populations is commonly established through the use of the PSEUROT program and 1H-1H coupling constant data (3J) obtained from high-resolution 1H NMR spectra. PSUEROT essentially 'builds' a pair of N/S conformers that best replicate in experimental J's. To do this building properly the user must specify, from a limited selection within PSEUROT, the 'A' and 'B' parameters that correlate the endocyclic torsion angles (which define the N/S conformations) to the exocyclic H-H torsion angles (which form the basis of the calculated 3J's). A significant bottleneck to the use of PSEUROT is that the A and B parameters for novel furanose rings not in the PSEUROT database must somehow be derived. Historically, the A and B parameters have been obtained from either from a large body of crystal structures or from high-level quantum mechanical structures. Herein we report that A and B parameters derived from molecular mechanics methods (Amber) provide PSEUROT results virtually indistinguishable from ab initio methods, greatly facilitating the use of PSEUROT.

Conformational analysis of nucleosides: A combined PSEUROT/molecular mechanics approach

248th National Meeting (2014)

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