2-Deoxy--D-ribofuranosylamine: Quantum Mechanical Calculations of Molecular Structure and NMR Spin-Spin Coupling Constants in Nitrogen-Containing Saccharides Francis Cloran, ² Yuping Zhu, ² John Osborn, ² Ian Carmichael,* ,‡ and Anthony S. Serianni* ,² Contribution from the Department of Chemistry and Biochemistry and the Radiation Laboratory, UniVersity of Notre Dame, Notre Dame, Indiana 46556 ReceiVed December 30, 1999. ReVised Manuscript ReceiVed April 10, 2000 Abstract: Ab initio molecular orbital (MO) and density functional theory (DFT) calculations using a polarized split-valence basis set have been performed on 2-deoxy--D-ribofuranosylamine (2-deoxy--D-erythro- pentofuranosylamine) in its unprotonated (3) and protonated (4) forms. Structural data confirm three previously reported factors influencing bond lengths in aldofuranosyl rings, and suggest the existence of a new 1,4-lone pair effect. Conformational energy profiles for 3 and 4 were compared to that described recently for 2-deoxy- -D-ribofuranose (2-deoxy--D-erythro-pentofuranose) 5. Results show that preferred conformation and energy barriers to pseudorotation are affected significantly by changes in C1 substitution. N-Protonation of 3 reduces pseudorotational barriers, suggesting a more flexible ring relative to the unprotonated molecule. NMR spin- spin coupling constants involving C1 and H1 were calculated in 3 and 4 using DFT methods described previously (Cloran et al. J. Phys. Chem. 1999, 103, 3783-3795). Trends in computed couplings as a function of ring conformation and C1 substitution confirm prior predictions based on experimental observations in aminosugars and nucleosides. In general, one- and two-bond J CH and J CC values appear more influenced by O f N substitution and by N-protonation than vicinal 3 J CH and 3 J CC . These results will be useful in studies of related NMR scalar coupling constants in biologically relevant aminosugars and nucleosides, either free in solution or as components of oligosaccharides and oligonucleotides. Introduction It is well accepted that aldofuranosyl rings can exhibit considerable conformational flexibility in solution, either as free entities or as constituents of more complex biomolecules such as DNA and RNA. 1 This flexibility is commonly assumed to involve a two-state exchange between generalized North (N, 3 E) and South (S, 2 E) nonplanar conformers via a pseudorota- tional itinerary 2 (Scheme 1) or via inversion. 3 This two-state model derives mainly from studies of the biologically relevant -D-ribo and 2-deoxy--D-ribo (2-deoxy--D-erythro-pento) rings and is often assumed to operate in aldofuranosyl rings having other structures and configurations. The latter assump- tion, however, is not strictly valid, especially since a complete understanding of the effects of furanose structure on ring conformation and dynamics remains elusive. Such an under- standing would be valuable, since other ring configurations (e.g., R-D-arabino) and ring substitution patterns (e.g., glycosyl- amines) are encountered in biological systems. A key intermediate in the biosynthesis of purine ribonucle- otides is -D-ribofuranosylamine 5-phosphate 1, the glycosyl- amine derived from -D-ribofuranose 5-phosphate 2. 4 The amino substituent at C1 of 1 might be expected to exert a significant effect on ring conformation, leading to different preferred conformations for 1 and 2. This difference is anticipated because * Address correspondence to this author. ² Department of Chemistry and Biochemistry. ‡ Radiation Laboratory. (1) (a) Westhof, E.; Sundaralingam, M. J. Am. Chem. Soc. 1983, 105, 970-976. (b) Levitt, M.; Warshel, A. J. Am. Chem. Soc. 1978, 100, 2607- 2613. (c) Westhof, E.; Sundaralingam, M. J. Am. Chem. Soc. 1980, 102, 1493-1500. (d) Olson, W. K. J. Am. Chem. Soc. 1982, 104, 278-286. (e) Olson, W. K.; Sussman, J. L. J. Am. Chem. Soc. 1982, 104, 270-278. (f) Harvey, S. C.; Prabhakaran, M. J. Am. Chem. Soc. 1986, 108, 6128-6136. (g) Pearlman, D. A.; Kim, S.-H. J. Biomol. Struct. Dyn. 1985, 3, 99-124. (2) Altona, C.; Sundaralingam, M. J. Am. Chem. Soc. 1972, 94, 8205- 8212. (3) Westhof, E.; Sundaralingam, M. J. Am. Chem. Soc. 1983, 105, 970- 976. (4) Schendel, F. J.; Cheng, Y. S.; Otvos, J. D.; Wehrli, S.; Stubbe, J. Biochemistry 1988, 27, 2614-2623. Scheme 1 Pseudorotational itinerary of an aldofuranose ring P 10.1021/ja994544g CCC: $19.00 © xxxx American Chemical Society PAGE EST: 13.3 Published on Web 00/00/0000