The semi-empirical PM3 SCF-MO method is used to investigate the Wagner-Meerwein migration of various groups during the pinacol-pinacolone rearrangement of some acyclic systems. Pinacol first protonates and dehydrates to form a carbocation that undergoes a 1,2-migration to form a protonated ketone, which then deprotonates to yield the pinacolone product. We study the Wagner-Meerwein migration of hydride, methyl, ethyl, isopropyl, t-butyl, phenyl and heterocylic 2-, 3-and 4-pyridyl groups in various acyclic 1,2-diol (pinacol) systems as they rearrange to pinacolones. This 1,2-migration involves a three-centred moiety in the cationic transition state. The migratory aptitude predicted here follows the order: hydride > t-butyl > isopropyl > ethyl > methyl > phenyl, which accords well with available experimental data and/or chemical intuition, reflecting also on the ability of the group involved to carry positive charge in the transition state. The structure of the migrating group (whether aliphatic or aromatic) within the transition state also supports the stabilising role of delocalisation of positive charge for reaction feasibility. Geometrical and thermodynamic considerations coincide in assigning the following order to relative "earliness" of the transition state along the reaction pathway: t-butyl > isopropyl > phenyl > methyl > 2-pyridyl > 4-pyridyl.

When DNA is damaged by ionizing radiation, the genes in a cell may acquire mutations or the cell could die. The smallest known DNA-damaging unit is an electron, often low-energy secondary electrons. Additional electrons and transfers involving hydrogen atoms, protons, and hydride anions can damage DNA subunits, including individual nucleobases and nucleoside pairs. Researchers would like to better understand the molecular mechanisms involved in DNA damage from ionizing radiation. In this Account, we highlight our theoretical investigations of the molecular mechanisms of DNA damage using quantum mechanical models. Our investigations use robust theoretical methods with computations conducted in the gas phase and with solution models. We calculate adiabatic electron affinities (AEAs), which describe the energetics of electronic attachment to closed-shell DNA subunits, for the free bases, nucleosides, nucleotides, base pairs, and single and double DNA strand units. Electron affinities for free nucleobases yield the order uracil > thymine > cytosine > guanine > adenine and the same order for the DNA nucleosides, mononucleotides, and nucleoside 3',5'-diphosphates. AEA values increase steadily with the size and complexity of the system because of greater hydration, glycosylation, nucleotide formation, and base pairing. We predict and experimental results partially confirm that most of the more complex and hydrated species are observable as radical anions. Our modeling studies indicate that depyrimidination reactions of radical anion nucleosides release cytosine more often than thymine. Recent experimental results support those findings. Our theoretical studies of DNA base-pair radical anions predict increases in electron affinity accompanying H bonding and solvation. Electron addition facilitates some proton transfers in these pairs, which results in strongly perturbed pairing configurations. Of all nucleobase moieties within the more complex radical anion systems, thymine is best able to retain a negative charge. Charge and spin are well-separated in some of these systems. Radical species derived via hydrogen abstraction from DNA subunits yield large AEA values because they form closed-shell anions. Our studies predict single-strand breaks following H abstraction from nucleotides. Some H-abstraction processes in the DNA base pairs lead to severe distortions in pairing configuration based on our calculations. This body of systematic theoretical studies provides realistic descriptions of some events that lead to elementary DNA lesions, while providing rationalizations for many observed phenomena. Such approaches can lead to the design of new experiments, which would contribute to our understanding of the chemical physics of nucleic acids.

Diiron paddlewheel‐ or lantern‐type complexes comprise an interesting subclass of binuclear iron complexes, existing with digonal, trigonal, and tetragonal ligand arrays. Experimentally known members show Fe−Fe bonds of lengths ranging from 2.13 to 2.73 Å, with Fe−Fe bond orders ranging from 0.5 to 2. Truncated models for 30 experimentally characterized diiron paddlewheel‐type complexes have been studied by DFT using the M06‐L functional, reproducing the Fe−Fe bond lengths quite well. In addition, we use DFT to treat three series of model diiron complexes Fe2Lx (x=2, 3, 4) in various low‐lying spin states, L being the unsubstituted formamidinate, guanidinate, and formate ligands (along with a series of axially ligated formate complexes) in order to predict ground state spin multiplicities, Fe−Fe bond lengths, and features of the ligand arrays. The ground states all have high spin multiplicities (septets, octets, and nonets). Formal bond order (fBO) values are suggested for the Fe−Fe bonds in these 61 complexes using an electron bookkeeping procedure, in addition to the Fe−Fe bond orders obtained by metal‐metal MO analysis for ground state species. Fe−Fe bond orders up to 3 are noted in some excited states. Deviations from D3h and D4h symmetry are noted for many trigonal and tetragonal complexes, being attributed to inherent Jahn‐Teller distortions. The formamidinate and guanidinate series show many similarities, while the formate series differs from these two in several aspects. From these results, ranges are derived for Fe−Fe bond lengths of orders 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0. The Fe−Fe bond length ranges for these non‐carbonyl lantern complexes are found to be appreciably lower than the corresponding ranges for diiron complexes with carbonyl ligands as compiled earlier from computational and experimental results.

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Interactions of the Ni 2+ , Cu 2+ , and Zn 2+ ions with the simplest dipeptide glycylglycine (GlyGly) are explored using various experimental and computational techniques. Solid and aqueous phase syntheses of the metalated GlyGly complexes (by solid-state grinding and by coprecipitation respectively) lead to the same products, as confirmed by physicochemical and spectral properties which indicate metal-coordination through the −NH 2 and −CO 2 − groups of the dipeptide. Phase-diagram and kinetic studies of the solid-phase reaction between GlyGly and copper acetate suggest that complexation occurs in 1:2 (metal/ligand) stoichiometry via a facile kinetic pathway (a barrier of only 22.22 kJ/mol). The right-handed α-helical conformer of GlyGly is considered in DFT modeling studies in gas and aqueous phases elucidating the effects of metalation and solvation upon structural, electronic, and vibrational properties of the complexes. The complexes are found to follow the stability order Cu 2+ > Ni 2+ > Zn 2+ corroborating the Irving-Williams series. The Ni(GlyGly) 2 complex is predicted to exist in its low-spin state. Hydration effects on structural aspects of the complexes are also investigated computationally. The BHandHLYP/6-311++G(d,p) level describes the Cu(GlyGly) 2 complex more efficiently than the B3LYP/6-311++G(d,p) level (which, however, better predicts the vibrational spectra of the systems). Absorption titration experiments with calf thymus DNA together with in silico docking and molecular mechanical studies reveal that these metal−dipeptide complexes are DNA minor-groove binders primarily through Hbonding interactions, yielding a DNA-binding affinity order of Ni 2+ > Zn 2+ > Cu 2+ .