Pseudorotation of the sugar moiety in pyrimidine nucleosides occurs on the same time-scale as the overall tumbling:2H NMR relaxation time study

Abstract

The molecular motions of speci-cally deuterated thymidines 1E5a and two C-3-deuterated allofura- noses 6 and 7 were studied through temperature-dependent 2H and 13C relaxation times. Deuterium relaxation times in 1E5a were found in the range 20E270 ms between 278 and 358 K, respectively. Interpretation of deuterium relaxation time, which is dominated by quadrupole mechanism, gave the e†ective rotational correlation time T 1 in the range from 62.5 ps in 2@,6-diDT (4) to 117.5 ps in 6-DT (3) at 278 K. The values are reduced to 9.3 ps (q eff ) q eff in 2@,6-diDT (4) to 16 ps in 6-DT (3) at 358 K. The values for 6 and 7 are 93.9 and 100.4 ps, respectively, at 278 q eff K, and are reduced to 19.8 and 22.6 ps, respectively, at 328 K. A deuterium quadrupole coupling constant (e2qQ/h) of 167 kHz was calculated from 2H and 13C relaxation times in 2@-DT (1). Arrhenius-type analysis of temperature- dependent deuterium relaxation times in 1E7 gave apparent activation energies in the range 20E23 (^0.9) kJ T 1 mol~1. Deuterium in anh-6-DT (5a) served as a reference for the evaluation of the activation energy of the overall molecular reorientation in the conformationally free counterparts 1E4 due to the fact that rotation across s and repuckering are prevented by its structure. The comparison of the apparent activation energies from the N H S conformationally free nucleosides 1E4 with those from the constrained analogue 5a and abasic sugars 6 and 7 suggests that their internal local motions are heavily coupled with the overall molecular reorientation, thus pre- venting the estimation of the pseudorotation energy barrier. 1998 John Wiley & Sons, Ltd. (