Vibrational Force Field Calculations of Ara-A. Application to the Analysis of Its Infrared and Raman Spectra

Abstract

The vibrational spectra of the arabinonucleoside 9-β-d-arabinofuranosyladenine, ara-A, are reported. Ara-A is of interest because of its antiviral activity. An accurate knowledge of the vibrational modes is a valuable help for the elucidation of drug−nucleotide and drug−enzyme interactions. The FTIR and FT-Raman spectra of ara-A were recorded from 4000 to 30 cm-1. A hexadeuterated derivative (deuteration at C8, the amino and hydroxyl groups) was synthesized, and its spectra were also used for the vibrational analysis of ara-A. Theoretical frequencies as well as the potential energy distribution of the vibrational modes of ara-A were calculated using the ab initio HF/3-21G method, the semiempirical PM3 method, and two valence force fields. The results obtained are compared in order to show the accuracy and reliability of each method. The observed spectra and the vibrational frequencies of ara-A are assigned considering the potential energy distributions and the observed band shifts by deuteration. Scaled ab initio and PM3 frequencies are in a good agreement with the experimental data. The valence force field was found to reproduce them with enough accuracy when a large set of harmonic force constants is used. Previous normal coordinate analyses of the adenine and related molecules are compared with these results.

Ab initio Hartree–Fock/6‐31G** calculation on 9‐β‐D‐arabinofuranosyladenine‐5′‐monophosphate molecule: Application to the analysis of its IR and Raman spectra

“…Tsuboi et al 35 recently proposed a new assignment for the HOCЈ 5 OHЈ scissoring in thymidine, locating this vibration at 1481 cm Ϫ1 . Nevertheless, our results for 5Ј-ara-AMP at the HF/6-31G** level and for other nucleotides and nucleosides 16,37,44,45 are consistent with their previous assignment. 25,58,63 The IR band at 1360 cm Ϫ1 also shows significant contributions from both the sugar and base moieties, the latter being somewhat more important.…”

“…3,15 The IR and Raman spectra of the ara-A molecule and their proposed assignment according to ab initio Hartree-Fock (HF)/3-21G calculations were reported. 16 In the present work, we extend the study to ara-A-5Ј-monophosphate. We present the vibrational analysis of 5Ј-ara-AMP and two deuterium derivatives synthesized for this purpose.…”

“…Fitting this value, the calculation predicts the antisymmetric stretch, a (NH 2 ), at 3589 cm Ϫ1 . The bands at 3332 (3325 cm Ϫ1 in Raman) and 3278 cm Ϫ1 (3280 cm Ϫ1 , strong in Raman) are assigned to the OЈ 3 OH and OЈ 2 OH stretches (by comparison with other nucleosides and nucleotides 16,37,44,45,55,56 ), while those that appear at 3250 (very strong in IR) and 3225 cm Ϫ1 (resolved by the second derivative) are attributed to the two OOH groups of the phosphate group. Calculations predict that these bands should shift by …”

“…16,20,21,24,26,56,57 The scissoring vibration of the amino group appears in this region 16,17,19 -21,24,26,57 and contributes significantly, according to the HF/6-31G** ab initio treatment, to the modes giving rise to the bands at 1696 (very strong in IR and weak in Raman, 35% contribution), 1611 (medium intensity in IR and Raman, 14% contribution), and 1556 cm Ϫ1 (medium intensity in IR and strong in Raman, 11% contribution). In these three cases the scis- Proposed assignment and potential energy distribution (PED) of the vibrational normal modes Types of vibration: , stretching; ␦, in plane bending; , out of plane bending; , torsion.…”

“…It is similar to that found for the ara-A molecule. 16 The band (weak in IR and Raman) at 1293 cm Ϫ1 is also due to pyrimidine ring vibrations; the Raman band that appears at 1287 cm Ϫ1 is originated almost exclusively by the imidazole ring, together with small contributions from the sugar. This band is displaced by deuteration at the C 8 position.…”