Electron attachment to DNA and RNA nucleobases: An EOMCC investigation

We report a benchmark theoretical investigation of both vertical and adiabatic electron affinities of DNA and RNA nucleobases: adenine, guanine, cytosine, thymine, and uracil using equation of motion coupled cluster method. The vertical electron affinity (VEA) values of the first five states of the DNA and RNA nucleobases are computed. It is observed that the first electron attached state is energetically accessible in gas phase. Furthermore, an analysis of the natural orbitals exhibits that the first electron attached states of uracil and thymine are valence‐bound in nature and undergo significant structural changes on attachment of an extra electron, which reflects in the deviation of the adiabatic electron affinity (AEA) than that of the vertical ones. Conversely, the first electron attached states of cytosine, adenine, and guanine are in the category of dipole‐bound anions. Their structure, by and large, remain unaffected on attachment of an extra electron, which is evident from the observed small difference between the AEA and VEA values. VEA and AEA values of all the DNA and RNA nucleobases are found to be negative, which implies that the first electron attached states are not stable rather quasi bound. The results of all previous theoretical calculations are out of track and shows large deviation with respect to the experimentally measured values, whereas, our results are found to be in good agreement. Therefore, our computed values can be used as a reliable standard to calibrate new theoretical methods. © 2015 Wiley Periodicals, Inc.     

Interaction of dinuclear ruthenium(II) supramolecular cylinders with DNA: sequence-specific binding, unwinding, and photocleavage

Metallosupramolecular chemistry was used to design a new class of synthetic agents, namely, tetracationic supramolecular cylinders, that bind strongly and noncovalently in the major groove of DNA. To gain additional information on interactions of the cylinders with DNA we explored DNA unwinding and sequence-specific binding properties, as well as DNA photonuclease activity of ruthenium(II) metallosupramolecular cylinder [Ru(2)L(3)](4+), where L is a bis-pyridylimine ligand. We found that [Ru(2)L(3)](4+) unwinds negatively supercoiled plasmid DNA and exhibits binding preference to regular alternating purine-pyrimidine sequences in a similar way to the [Fe(2)L(3)](4+) analogue. Photocleavage studies showed that, unlike [Fe(2)L(3)](4+), [Ru(2)L(3)](4+) induces single-strand breaks on irradiation by visible and UVA light and cleaves DNA mainly at guanine residues contained preferentially in regularly alternating purine-pyrimidine nucleotides. As [Ru(2)L(3)](4+) binds and cleaves DNA in a sequence-dependent manner, it may provide a useful tool for basic and applied biology, such as for controlled manipulation of the genome.     

Homolytic X-H Bond Cleavage at a Gold(III) Hydroxide: Insights into One-Electron Events at Gold

C(sp³)-H and O−H bond breaking steps in the oxidation of 1,4-cyclohexadiene and phenol by a Au(III)-OH complex were studied computationally. The analysis reveals that for both types of bonds the initial X−H cleavage step proceeds via concerted proton coupled electron transfer (cPCET), reflecting electron transfer from the substrate directly to the Au(III) centre and proton transfer to the Au-bound oxygen. This mechanistic picture is distinct from the analogous formal Cu(III)-OH complexes studied by the Tolman group (J. Am. Chem. Soc. 2019 , 141, 17236–17244), which proceed via hydrogen atom transfer (HAT) for C−H bonds and cPCET for O−H bonds. Hence, care should be taken when transferring concepts between Cu−OH and Au−OH species. Furthermore, the ability of Au−OH complexes to perform cPCET suggests further possibilities for one-electron chemistry at the Au centre, for which only limited examples exist.     

Electron attachment to the DNA bases adenine and guanine and dehydrogenation of their anionic derivatives: Density functional study

Density functional theory (DFT) calculations have been used to explore electron attachment to the purines adenine and guanine and their hydrogen atom loss. Calculations show that the dehydrogenation at the N9 site in the adenine and guanine transient anions is the lowest‐cost channel of hydrogen loss, and the N9? H bond scission has Gibbs free energies of dissociation ΔG° of 8.8 kcal mol^?1 for the anionic adenine and 13.9 kcal mol^?1 for the anionic guanine. The relatively high feasibility of low‐energy electron (LEE)‐induced N9? H bond cleavage in the purine nucleobases arises from high electron affinities of their H‐deleted counterparts. Unlike adenine, other N? H bond dissociations are competitive with the N9? H bond fission in the anionic guanine. The replacement of hydrogen in the ring of purine has a significant effect on the N9? H bond fragmentation. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Simulations of DNA coiling around a synthetic supramolecular cylinder that binds in the DNA major groove

In this work we present the results of a molecular simulation study of the interaction between a tetracationic bis iron(II) supramolecular cylinder, [Fe2(C25H20N4)3]4+, and DNA. This supramolecular cylinder has been shown to bind in the major groove of DNA and to induce dramatic coiling of the DNA. The simulations have been designed to elucidate the interactions that lead the cylinder to target the major groove and that drive the subsequent DNA conformational changes. Three sets of multi-nanosecond simulations have been performed: one of the uncomplexed d(CCCCCTTTTTCC) d(GGAAAAAGGGGG) dodecamer; one of this DNA complexed with the cylinder molecule; and one of this DNA complexed with a neutralised version of the cylinder. Coiling of the DNA was observed in the DNA-cylinder simulations, giving insight into the molecular level nature of the supramolecular coiling observed experimentally. The cylinder charge was found not to be essential for the DNA coiling, which implies that the DNA response is moderated by the short range interactions that define the molecular shape. Cylinder charge did, however, affect the integrity of the DNA duplex, to the extent that, under some circumstances, the tetracationic cylinder induced defects in the DNA base pairing at locations adjacent to the cylinder binding site.     

Computational Study of Proton Transfer in Tautomers of 3‐ and 5‐Hydroxypyrazole Assisted by Water

The tautomerism of 3‐ and 5‐hydroxypyrazole is studied at the B3LYP, CCSD and G3B3 computational levels, including the gas phase, PCM–water effects, and proton transfer assisted by water molecules. To understand the propensity of tautomerization, hydrogen‐bond acidity and basicity of neutral species is approached by means of correlations between donor/acceptor ability and H‐bond interaction energies. Tautomerism processes are highly dependent on the solvent environment, and a significant reduction of the transition barriers upon solvation is seen. In addition, the inclusion of a single water molecule to assist proton transfer decreases the barriers between tautomers. Although the second water molecule further reduces those barriers, its effect is less appreciable than the first one. Neutral species present more stable minima than anionic and cationic species, but relatively similar transition barriers to anionic tautomers.     

Streptococcal Hyaluronate Lyase Reveals the Presence of a Structurally Significant CH⋅⋅⋅O Hydrogen Bond

Carbon‐donated hydrogen bonds (CDHBs) are weak forms of hydrogen bonding (0.5–1.0 kcal mol^?1) that are difficult to detect, and thus their roles in the structure and functionality of chemical systems often go unrecognized. Utilizing a computational approach, the existence of a structurally significant CDHB in the medically relevant protein Streptococcus pneumoniae hyaluronate lyase (SpnHL) is affirmed. The structure of a tetrapeptide fragment model containing the CDHB was optimized with second‐order perturbation theory. From this, a CDHB with bond distance and angle consistent with previously discovered CDHBs and comparable to neighboring traditional HBs in the fragment model was found. The CDHB competes with another donor T253 OH, whereby the two alternate in strength between protein conformations, imbuing αHelix 3 appreciable flexibility. The CDHB seems to exist in spite of torsional and steric strain on the donor methyl group. It is postulated that the CDHB could aid in either counteracting the macrodipole of αHelix 3 or protecting the A249 CO from destabilizing interactions with the adjacent solvent. Employing the energy gradients from the optimization, the torque generated by the fragment model was computed, which accurately predicts the direction of rotation of αHelix 3 observed from experiment. A strongly correlated motion between αHelix 3 and αHelices 2, 4, and 5 was noted, which the interactions of the fragment model help drive by generating a torque much larger than necessary to rotate just αHelix 3. Considering these results, we conclude that CDHBs should be considered as possible beneficial components of chemical and biological phenomena.     

On the Mechanism of Long-Range Electron Transfer through DNA

Hopping between bases of similar redox potentials is the mechanism by which charge transport occurs through DNA. This was shown by rate measurements performed with double strands 1 – 3 . This mechanism explains why hole transfer displays a strong sequence dependence, and postulates that electron transfer in unperturbed DNA should not be dependent on the sequence.     

Electron Attachment to Hydrated Oligonucleotide Dimers: Guanylyl‐3′,5′‐Cytidine and Cytidylyl‐3′,5′‐Guanosine

The dinucleoside phosphate deoxycytidylyl‐3′,5′‐deoxyguanosine (dCpdG) and deoxyguanylyl‐3′,5′‐deoxycytidine (dGpdC) systems are among the largest to be studied by reliable theoretical methods. Exploring electron attachment to these subunits of DNA single strands provides significant progress toward definitive predictions of the electron affinities of DNA single strands. The adiabatic electron affinities of the oligonucleotides are found to be sequence dependent. Deoxycytidine (dC) on the 5′ end, dCpdG, has larger adiabatic electron affinity (AEA, 0.90 eV) than dC on the 3′ end of the oligomer (dGpdC, 0.66 eV). The geometric features, molecular orbital analyses, and charge distribution studies for the radical anions of the cytidine‐containing oligonucleotides demonstrate that the excess electron in these anionic systems is dominantly located on the cytosine nucleobase moiety. The π‐stacking interaction between nucleobases G and C seems unlikely to improve the electron‐capturing ability of the oligonucleotide dimers. The influence of the neighboring base on the electron‐capturing ability of cytosine should be attributed to the intensified proton accepting–donating interaction between the bases. The present investigation demonstrates that the vertical detachment energies (VDEs) of the radical anions of the oligonucleotides dGpdC and dCpdG are significantly larger than those of the corresponding nucleotides. Consequently, reactions with low activation barriers, such as those for O? C σ bond and N‐glycosidic bond breakage, might be expected for the radical anions of the guanosine–cytosine mixed oligonucleotides.     

Excess‐Electron Injection and Transfer in Terthiophene‐Modified DNA: Terthiophene as a Photosensitizing Electron Donor for Thymine,Cytosine, and Adenine

Excess‐electron transfer (EET) in DNA has attracted wide attention owing to its close relation to DNA repair and nanowires. To clarify the dynamics of EET in DNA, a photosensitizing electron donor that can donate an excess electron to a variety of DNA sequences has to be developed. Herein, a terthiophene (3T) derivative was used as the photosensitizing electron donor. From the dyad systems in which 3T was connected to a single nucleobase, it was revealed that ¹3T* donates an excess electron efficiently to thymine, cytosine, and adenine, despite adenine being a well‐known hole conductor. The free‐energy dependence of the electron‐transfer rate was explained on the basis of the Marcus theory. From the DNA hairpins, it became clear that ¹3T* can donate an excess electron not only to the adjacent nucleobase but also to the neighbor one nucleobase further along and so on. From the charge‐injection rate, the possibilities of smaller β value and/or charge delocalization were discussed. In addition, EET through consecutive cytosine nucleobases was suggested.     

Modeling Charge Transfer Reactions by Hopping between Electronic Ground State Minima: Application to Hole Transfer between DNA Bases

In this paper, we extend the previously described general model for charge transfer reactions, introducing specific changes to treat the hopping between energy minima of the electronic ground state (i.e., transitions between the corresponding vibrational ground states). We applied the theoretical–computational model to the charge transfer reactions in DNA molecules which still represent a challenge for a rational full understanding of their mechanism. Results show that the presented model can provide a valid, relatively simple, approach to quantitatively study such reactions shedding light on several important aspects of the reaction mechanism.