This thesis consists of seven research publications concerning (i) pK_a studies of nucleobases in model nucleotides to understand why RNA duplexes are more stable than DNA duplexes (Paper I), (ii) the role of Me(T)-π interactions in the relative stability of DNA-RNA heteroduplexes (Paper II), (iii) pK_a measurements in nucleotides with different 2′-substituents (paper III), (iv) a conformation study of constrained sugars and a pK_a study of 1-thyminyl to reveal effect of sugar constraints on the pK_a of the nucleobase (paper IV), (v) NMR and MD studies of 1′, 2′-oxetane constrained thymidine incorporated Dickerson Drew dodecamer (paper V), (vi) the sequence dependent pK_a perturbation of 9-guaninyl moeity in single stranded (ss) DNA and RNA (paper VI), (vii) the non identical chemical nature of internucleotidic phosphates in (ss) RNA using ³¹P NMR (paper VI), and an alkaline hydrolysis study of phosphodiesters in ssRNAs (paper VII). The architecture of DNA and RNA molecules is determined by (a) hydrogen bonding (b) base stacking (c) a variety of additional non-covalent interactions. In paper (I) we showed that A-U and G-C base pairings in RNA are more stable than A-T and G-C base pairings in DNA by 4.3 and 1 kJ mol^-1 respectively. Me(T)-π interaction plays a dominant role in the relative stability of DNA-RNA duplexes (paper II). In paper III and IV, we have shown that 1′ , 2′- oxetane and azetidine rings have strong inductive effect on pyrimidine bases, and that the H2′-sugar proton can be the marker to understand the pseudoaromaticity of pyrimidine bases, as well as increasing constraints in sugar reducing the basicity of nucleobases. A 1′, 2′-oxetane locked thymidine (T) moiety deforms the local structure of Dickerson-Drew dodecamer, d(CGCGAATTCGCG)₂- investigated by High resolution NMR and MD study, as is discussed in the paper V. In papers VI and VII, we showed sequence context dependent pK_a (N1) of 9-guaninyl perturbation in (ss) DNAs and RNAs and the non identical chemical nature of inter-nucleotidic phosphate groups in single stranded RNAs.