Interpretation of Indirect Nuclear Spin−Spin Couplings in Isomers of Adenine: Novel Approach to Analyze Coupling Electron Deformation Density Using Localized Molecular Orbitals

Abstract

Adenine, an essential building block of nucleic acids present in all living systems, can occur in several tautomeric forms. The phenomenon of tautomerism can be investigated by several experimental methods, including nuclear magnetic resonance. In this study, long-range (1)H-(13)C and (1)H-(15)N coupling constants for N-alkyl derivatives related to four tautomers of adenine are investigated in DMSO and DMF solutions. To investigate the structural dependence of the coupling constants and to understand how polarization propagates in the system, Fermi contact (FC) terms were calculated for the individual isomers and analyzed by using density functional theory (DFT), and the coupling pathways were visualized using real-space functions. The coupling electron deformation densities (CDD) of several (1)H-X (X = (13)C, (15)N) pairs are evaluated and compared. In order to analyze the CDD in more detail, a new approach to break down the CDD into contributions from Boys or Pipek-Mezey localized molecular orbitals (LMOs) has been developed. A similar approach has been applied to split the value of the FC contribution to the J coupling into the LMO contributions. On the basis of chemical concepts, the contributions of sigma-bonds, pi-electrons, and lone pairs of electrons are discussed. The lone pair of electrons at the nitrogen atom contributes significantly to the (1)H-C horizontal line(15)N coupling, whereas the (1)H-C=N-(13)C coupling is affected in a somewhat different way. Surprisingly, the contribution of the intervening C horizontal lineN bond to the FC term for (1)H-C=(15)N coupling originates exclusively in sigma-electrons, with a vanishingly small contribution calculated for the pi-electrons of this fragment. This behavior is rationalized by introducing the concept of "hard and soft J elements" derived from the polarizability of the individual components.

Chemical Shift Tensors in Isomers of Adenine: Relation to Aromaticity of Purine Rings?

“…The basic framework topologies of the 3-, 7-, and 9-benzyladenine isomers (Scheme 1), determined by single-crystal X-ray diffraction analysis, were published previously. [25] The unit cell of 3-benzyladenine (1) contains four molecules, situated at the edges, with two benzyl groups pointing inside and two pointing outside of the cell. The four 7-benzyladenine (2) molecules have the same spatial arrangement, but there are four water molecules in the unit cell as well-this isomer crystallizes as a monohydrate.…”

Solvent‐directed Regioselective Benzylation of Adenine: Characterization of N9‐benzyladenine and N3‐benzyladenine

“…The majority of papers have identified this minor isomer to be N7-benzyladenine [10,11] while two groups identified this isomer as N3-benzyladenine [8,9]. It is commonly reported that the reaction of adenine with an alkyl halide at elevated temperatures in the presence of base yields the N9 and N7 regioisomers, whereas in the absence of base yields N3-alkylated adenine [13][14][15][16][17][18][19], and it has been reasoned that the formation of the N9/N7 regioisomers can be explained in terms of the dominance of the adenine tautomers, N9-H and N7-H [20]. Our aim was therefore to synthesize sufficient quantities of the minor benzyladenine regioisomer to allow for a full characterization by X-ray crystallography and two-dimensional NMR techniques.…”

The Structures of Uncommon Cationic N‐alkenyl Purine and Pyrimidine Bases

“…The 3‐subsituted adenine derivative, 3‐(butenyl)adeninium bromide ( 3 ), is somewhat more common, with structures of both neutral [3‐Et , CH 2 Ph , CH 2 C(H)CMe 2 , ribose ] and cationic [3‐Me, chloride or indole‐3‐acetate as counterion] structures previously reported. The asymmetric unit of 3 comprises a single molecule interacting with the bromide counterion via two hydrogen bonds (Fig.…”