How divalent cations interact with the internal channel site of guanine quadruplexes

The formation of guanine quadruplexes (GQ) in DNA is crucial in telomere homeostasis and regulation of gene expression. Pollution metals can interfere with these DNA superstructures upon coordination. In this work, we study the affinity of the internal GQ channel site towards alkaline earth metal (Mg2+, Ca2+, Sr2+, and Ba2+), and (post-)transition metal (Zn2+, Cd2+, Hg2+, and Pb2+) cations using density functional theory computations. We find that divalent cations generally bind to the GQ cavity with a higher affinity than conventional monovalent cations (e. g. K+). Importantly, we establish the nature of the cation-GQ interaction and highlight the relationship between ionic and nuclear charge, and the electrostatic and covalent interactions. The covalent interaction strength plays an important role in the cation affinity and can be traced back to the relative stabilization of cations' unoccupied atomic orbitals. Overall, our findings contribute to a deeper understanding of how pollution metals could induce genomic instability.Theoretical Chemistr

Sigma-electrons responsible for cooperativity and ring equalization in hydrogen-bonded supramolecular polymers

We have quantum chemically analyzed the cooperative effects and structural deformations of hydrogen-bonded urea, deltamide, and squaramide linear chains using dispersion-corrected density functional theory at BLYP-D3(BJ)/TZ2P level of theory. Our purpose is twofold: (i) reveal the bonding mechanism of the studied systems that lead to their self-assembly in linear chains; and (ii) rationalize the C-C bond equalization in the ring moieties of deltamide and squaramide upon polymerization. Our energy decomposition and Kohn-Sham molecular orbital analyses reveal cooperativity in all studied systems, stemming from the charge separation within the sigma-electronic system by charge transfer from the carbonyl oxygen lone pair donor orbital of one monomer towards the sigma* N-H antibonding acceptor orbital of the neighboring monomer. This key orbital interaction causes the C=O bonds to elongate, which, in turn, results in the contraction of the adjacent C-C single bonds that, ultimately, makes the ring moieties of deltamide and squaramide to become more regular. Notably, the pi-electron delocalization plays a much smaller role in the total interaction between the monomers in the chain.Theoretical Chemistr