LCAO Electronic Structure of Nucleic Acid Bases and Other Heterocycles and Transfer Integrals in B-DNA, Including Structural Variability

Abstract

To describe the molecular electronic structure of nucleic acid bases and other heterocycles, we employ the Linear Combination of Atomic Orbitals (LCAO) method, considering the molecular wave function as a linear combination of all valence orbitals, i.e., 2s, 2px, 2py, 2pz orbitals for C, N, and O atoms and 1s orbital for H atoms. Regarding the diagonal matrix elements (also known as on-site energies), we introduce a novel parameterization. For the non-diagonal matrix elements referring to neighboring atoms, we employ the Slater–Koster two-center interaction transfer integrals. We use Harrison-type expressions with factors slightly modified relative to the original. We compare our LCAO predictions for the ionization and excitation energies of heterocycles with those obtained from Ionization Potential Equation of Motion Coupled Cluster with Singles and Doubles (IP-EOMCCSD)/aug-cc-pVDZ level of theory and Completely Normalized Equation of Motion Coupled Cluster with Singles, Doubles, and non-iterative Triples (CR-EOMCCSD(T))/aug-cc-pVDZ level of theory, respectively, (vertical values), as well as with available experimental data. Similarly, we calculate the transfer integrals between subsequent base pairs, to be used for a Tight-Binding (TB) wire model description of charge transfer and transport along ideal or deformed B-DNA. Taking into account all valence orbitals, we are in the position to treat deflection from the planar geometry, e.g., DNA structural variability, a task impossible for the plane Hückel approach (i.e., using only 2pz orbitals). We show the effects of structural deformations utilizing a 20mer evolved by Molecular Dynamics.

Charge transport properties of ideal and natural DNA segments, as mutation detectors

“…The on-site energies and interaction integrals for all sequences were calculated using all valence orbitals of all atoms, according to the procedure described in Ref. 26 . For ideal sequences, the on-site energies are E A-T = −8.49 eV for the A-T base pair, and E G-C = −8.30 eV for the G-C base pair 26 .…”

“…Its HOMO value is E A−C = −8.43 eV, i.e., very close to the one of the A-T base pair. The HOMO (LUMO) interaction integrals between successive base pairs of ideal geometry, without mismatches, calculated with the method described in 26 , using all valence orbitals of all atoms, are listed in Table 2. Mutations and distortions change the values of interaction integrals; this effect is included in present work, using the same method 26 .…”

“…Table 1 HOMO (E H ) and LUMO (E L ) energies of ideal DNA bases, i.e., A, T, G, C and base pairs, i.e., A-T, G-C, A-C, obtained via LCAO with all valence orbitals 26 Table 2 Absolute values of interaction parameters between HOMOs (LU-MOs), |t LCAO |, for all possible combinations of successive base pairs, obtained via LCAO, using all valence orbitals, for close-to-ideal geometrical conformations 26 . All values are given in meV.…”

“…where the double spin degeneracy is not incorporated. The integrated density of states (IDOS) refers to the number of states that have energy smaller than E, and is defined as When such mismatches are introduced, the respective interaction integrals are modified, according the procedure described above, i.e., using the input geometry and LCAO with all valence orbitals of all atoms 26 . The eigenspectra and the corresponding DOS for the studied ideal and natural G 14 sequences with 7 A-C mismatch mutations, randomly positioned in the sequence, are presented in Fig.…”

An insight into therapeutic efficacy of heterocycles as histone‐modifying enzyme inhibitors that targets cancer epigenetic pathways

“…Literature suggests nitrogen heterocycles are present in 59% of US FDA‐approved drugs (Herav & Zadsirjan, 2020; Kerru et al, 2020). Apart from this, nucleic acid, which controls genetic information, includes these scaffolds (Mantela et al, 2021; Rodriguez et al, 2019) There are real challenges for researchers to overcome issues with lower cell permeability, selectivity, and more toxicity to develop enzyme‐specific inhibitors (Chaudhary, 2021; Chen & Xu, 2017). This review focuses on a comprehensive study of the recent reports on histone‐modifying enzyme inhibitors that include heterocycles in comparison with earlier reports (Huang et al, 2019; Ozyerli‐Goknar & Bagci‐Onder, 2021; Wapenaar & Dekker, 2016).…”