Effect of Guanine Adduct Size, Shape, and Linker Type on the Conformation of Adducted DNA: A DFT and Molecular Dynamics Study.

DNA is damaged through various exogenous sources (e.g., automobile exhaust, tobacco smoke, and processed foods), which can yield diverse C8-dG bulky aryl adducts. Adducts are known to induce structural changes to DNA that can lead to various biological outcomes, ranging from cell death to diseases such as cancer. Unfortunately, the relationship between the chemical composition of the damaged product, the adducted DNA structure, and the biological consequences is not well understood, which limits the development of disease detection and prevention strategies. The present study uses density functional theory (DFT) calculations and quintuplicate 1 µs molecular dynamics (MD) simulations to characterize the structure of DNA containing 21 model C8-dG adducts that systematically differ in size (phenyl to pyrenyl), shape (α (2,3), ß (3,4) fusion, or ring substitution), and nucleobase-aryl group linkage (N, O, and C-linked). DFT calculations reveal that the inherent structural features of the G nucleobase adducts are impacted by linker type and bulky moiety shape, but not size, with the conformational flexibility reducing with α-ring fusion and linker composition as N > O > C. These structural properties are maintained in nucleoside models, which also reveal an increased propensity for anti-to-syn rotation about the glycosidic bond with N < O < C linker type. Although these diverse chemical features do not influence the global structure of adducted DNA, the adducts differentially impact the conformation local to the adducted site, including the relative populations of structures with the bulky moiety in the major groove (B conformer) and intercalated (stacked) into the helix (S conformer). Specifically, while the smallest phenyl adducts favor the B conformation and the largest pyrenyl-derived adducts stabilize the S conformation, the B/S ratio decreases with an increase in ring size and N > O > C linker composition. The shape and size (length) of the adduct can further finetune the B/S ratio, with ß-fused naphthyl or α-fused phenanthryl N-linked adducts and O or C-linked adducts containing ring substitution increasing the prevalence of the S adducted DNA conformation. Overall, this work uncovers the significant effect of bulky moiety size and linker type, as well as the lesser impact of aryl group shape, on adducted DNA structure, which suggests differential replication and repair outcomes, and thereby represents an important step toward rationalizing connections between the structure and biological consequences of diverse DNA adducts.

Molecular Sn(II) precursors for room temperature deposition of crystalline elemental tin.

We report mild routes for the deposition of crystalline films of elemental tin via the formation and subsequent decomposition of unstable tin(II) hydrides. Specifically, we take advantage of efficient OtBu/H metathesis involving Sn(II) alkoxide precursors and the hydride source pinacolborane (HBpin); related -N(SiMe3)2/H exchange also afforded elemental tin as a final (insoluble) product.

Lewis Acid Behavior of MoF5 and MoOF4: Syntheses and Characterization of MoF5(NCCH3), MoF5(NC5H5)n, and MoOF4(NC5H5)n (n = 1, 2).

The Lewis acid-base adducts MoF5(NC5H5)n and MoOF4(NC5H5)n (n = 1, 2) were synthesized from the reactions of MoF5 and MoOF4 with C5H5N and structurally characterized by X-ray crystallography. Whereas the crystal structures of MoF5(NC5H5)2 and MoOF4(NC5H5)2 are isomorphous containing pentagonal-bipyramidal molecules, the fluorido-bridged, heptacoordinate [MoF5(NC5H5)]2 dimer differs starkly from monomeric, hexacoordinate MoOF4(NC5H5). For the weaker Lewis base CH3CN, only the 1:1 adduct, MoF5(NCCH3), could be isolated. All adducts were characterized by Raman spectroscopy in conjunction with vibrational frequency calculations. Multinuclear NMR spectroscopy revealed an unprecedented isomerism of MoOF4(NC5H5)2 in solution, with the pyridyl ligands occupying adjacent or nonadjacent positions in the equatorial plane of the pentagonal bipyramid. Paramagnetic MoF5(NC5H5)2 was characterized by electron paramagnetic resonance (EPR) spectroscopy as a dispersion in solid adamantane as well as in a diamagnetic host lattice of MoOF4(NC5H5)2; EPR parameters were computed using ZORA with the BPW91 functional using relativistic all-electron wave functions for Mo and simulated using EasySpin. Density functional theory calculations (B3LYP) and natural bond orbital analyses were conducted to elucidate the distinctive bonding and structural properties of all adducts reported herein and explore fundamental differences observed in the Lewis acid behavior of MoF5 and MoOF4.