Bishnu Thapa

Calculations of pKa’s and Redox Potentials of Nucleobases with Explicit Waters and Polarizable Continuum Solvation

The SMD implicit solvation model augmented with one and four explicit water molecules was used to calculate pKas and redox potentials of N-methyl-substituted nucleic acid bases guanine, adenine, cytosine, thymine, and uracil. Calculations were carried out with the B3LYP/6-31+G(d,p) level of theory. The same numbers of water molecules were hydrogen bonded to the neutral, protonated, and deprotonated nucleobases in their unoxidized and oxidized forms. The improvement in pKa1 involving neutrals and cations was modest. By contrast, the improvement in pKa2 involving neutrals and anions was quite significant, reducing the mean absolute error from 4.6 pKa units with no waters, to 2.6 with one water and 1.7 with four waters. For the oxidation of nucleobases, adding explicit waters did little to improve E(X(•),H(+)/XH), possibly because both species in the redox couple are neutral molecules at pH 7.

Density Functional Theory Calculation of pKa’s of Thiols in Aqueous Solution Using Explicit Water Molecules and the Polarizable Continuum Model

The pKas of substituted thiols are important for understanding their properties and reactivities in applications in chemistry, biochemistry, and material chemistry. For a collection of 175 different density functionals and the SMD implicit solvation model, the average errors in the calculated pKas of methanethiol and ethanethiol are almost 10 pKa units higher than for imidazole. A test set of 45 substituted thiols with pKas ranging from 4 to 12 has been used to assess the performance of 8 functionals with 3 different basis sets. As expected, the basis set needs to include polarization functions on the hydrogens and diffuse functions on the heavy atoms. Solvent cavity scaling was ineffective in correcting the errors in the calculated pKas. Inclusion of an explicit water molecule that is hydrogen bonded with the H of the thiol group (in neutral) or S(-) (in thiolates) lowers error by an average of 3.5 pKa units. With one explicit water and the SMD solvation model, pKas calculated with the M06-2X, PBEPBE, BP86, and LC-BLYP functionals are found to deviate from the experimental values by about 1.5-2.0 pKa units whereas pKas with the B3LYP, ωB97XD and PBEVWN5 functionals are still in error by more than 3 pKa units. The inclusion of three explicit water molecules lowers the calculated pKa further by about 4.5 pKa units. With the B3LYP and ωB97XD functionals, the calculated pKas are within one unit of the experimental values whereas most other functionals used in this study underestimate the pKas. This study shows that the ωB97XD functional with the 6-31+G(d,p) and 6-311++G(d,p) basis sets, and the SMD solvation model with three explicit water molecules hydrogen bonded to the sulfur produces the best result for the test set (average error -0.11 ± 0.50 and +0.15 ± 0.58, respectively). The B3LYP functional also performs well (average error -1.11 ± 0.82 and -0.78 ± 0.79, respectively).

The Mechanisms of Rectification in Au|Molecule|Au Devices Based on Langmuir–Blodgett Monolayers of Iron(III) and Copper(II) Surfactants†

Langmuir-Blodgett films of metallosurfactants were used in Au|molecule|Au devices to investigate the mechanisms of current rectification.

Improved pKa Prediction of Substituted Alcohols, Phenols, and Hydroperoxides in Aqueous Medium Using Density Functional Theory and a Cluster-Continuum Solvation Model

Acid dissociation constants (pKas) are key physicochemical properties that are needed to understand the structure and reactivity of molecules in solution. Theoretical pKas have been calculated for a set of 72 organic compounds with -OH and -OOH groups (48 with known experimental pKas). This test set includes 17 aliphatic alcohols, 25 substituted phenols, and 30 hydroperoxides. Calculations in aqueous medium have been carried out with SMD implicit solvation and three hybrid DFT functionals (B3LYP, ωB97XD, and M06-2X) with two basis sets (6-31+G(d,p) and 6-311++G(d,p)). The effect of explicit water molecules on calculated pKas was assessed by including up to three water molecules. pKas calculated with only SMD implicit solvation are found to have average errors greater than 6 pKa units. Including one explicit water reduces the error by about 3 pKa units, but the error is still far from chemical accuracy. With B3LYP/6-311++G(d,p) and three explicit water molecules in SMD solvation, the mean signed error and standard deviation are only -0.02 ± 0.55; a linear fit with zero intercept has a slope of 1.005 and R2 = 0.97. Thus, this level of theory can be used to calculate pKas directly without the need for linear correlations or thermodynamic cycles. Estimated pKa values are reported for 24 hydroperoxides that have not yet been determined experimentally.

Computational Study of Oxidation of Guanine by Singlet Oxygen (1.DELTA.g) and Formation of Guanine:Lysine Cross-Links

Oxidation of guanine in the presence of lysine can lead to guanine-lysine cross-links. The ratio of the C4, C5 and C8 crosslinks depends on the manner of oxidation. Type II photosensitizers such as Rose Bengal and methylene blue can generate singlet oxygen, which leads to a different ratio of products than oxidation by type I photosensitizers or by one electron oxidants. Modeling reactions of singlet oxygen can be quite challenging. Reactions have been explored using CASSCF, NEVPT2, DFT, CCSD(T), and BD(T) calculations with SMD implicit solvation. The spin contamination in open-shell calculations were corrected by Yamaguchis approximate spin projection method. The addition of singlet oxygen to guanine to form guanine endo- peroxide proceeds step-wise via a zwitterionic peroxyl intermediate. The subsequent barrier for ring closure is smaller than the initial barrier for singlet oxygen addition. Ring opening of the endoperoxide by protonation at C4-O is followed by loss of a proton from C8 and dehydration to produce 8-oxoGox . The addition of lysine (modelled by methylamine) or water across the C5=N7 double bond of 8-oxoGox is followed by acyl migration to form the final spiro products. The barrier for methylamine addition is significantly lower than for water addition and should be the dominant reaction channel. These results are in good agreement with the experimental results for the formation of guanine-lysine cross-links by oxidation by type II photosensitizers.

Molecular dynamics of methanol monocation (CH₃OH⁺) in strong laser fields.

Experimental studies by Yamanouchi and co-workers indicate that an intense 40 fs 800 nm laser pulse can cause CH3OH(+) to isomerizes during the pulse. The potential energy surfaces of methanol neutral, monocation, and singlet and triplet dication were explored using the CBS-APNO, CBS-QB3, CAM-B3LYP, and B3LYP levels of theory. Ab initio classical trajectories were calculated in the presence of a 2.9 × 10(14) W/cm(2) 800 nm laser field for methanol monocation on the ground state potential energy surface using the CAM-B3LYP/6-31G(d,p) level of theory. With only zero point energy, CH3OH(+) gained less than 15 kcal/mol from the 40 fs laser pulse, which was not enough to overcome any of the barriers for isomerization or fragmentation. To simulate extra energy deposited during the ionization process, 75, 100, and 125 kcal/mol of vibrational energy was added to the initial structures. After 400 fs, the distribution of product was CH2OH(+) + H (79-81%), HCOH(+) + H2 (9-13%), CH2OH2(+) (1-3%), CH3(+) + OH (1-3%), and CH2(+) + H2O (<0.5%). The estimated kinetic energy releases are in accord with experimental findings. Experimental results using a probe pulse to ionize CH3OH(+) to the dication showed substantial fraction C-O dissociation in both CH3OH(+) and CH2OH2(+) after the pulse. Because very few CH2OH2(+) → CH2(+) + H2O trajectories were seen in the simulation, the calculations suggest that some of the processes observed experimentally must occur on excited state surfaces or may be due to coupled nuclear-electron dynamics during the pump pulse.

Computational Study of the Radical Mediated Mechanism of the Formation of C8, C5, and C4 Guanine:Lysine Adducts in the Presence of the Benzophenone Photosensitizer

The oxidation of guanine by triplet benzophenone in the presence of lysine has been shown to produce mono- and dilysine-substituted spiroiminodihydantion products, 8-Lys-Sp and 5,8-diLys-Sp. The potential energy surfaces for C8, C5, and C4 nucleophilic addition have been mapped out using the B3LYP/aug-cc-pVTZ//B3LYP/6-31+G(d,p) level of density functional theory with the SMD solvation model and employing methylamine as a model for the side chain of lysine. Enthalpies, barrier heights, pKas, and reduction potentials were calculated for intermediates to find the lowest energy paths. For neutral methylamine plus guanine radical and neutral methylamine radical plus guanine, the barrier for addition at C8 is ca. 10 kcal/mol lower than that for addition at C5 and C4. The barriers for water addition at C8, C5, and C4 of guanine radical are 13-20 kcal/mol higher than that for methylamine addition at C8. Further oxidation and loss of a proton leads to 8-methylaminoguanine, the methylamino analogue of 8-oxo-7,8-dihydroguanine (8-oxoG). The barrier for the addition of a second methylamine at C5 of 8-methylaminoguanine is 4.5 kcal/mol lower than that for the corresponding addition of water. Nevertheless, if the concentration of methylamine (or lysine) is very low, water addition could be competitive with methylamine addition. This would lead to comparable fractions of 8-monosubstituted-Sp and 5-8-disubstituted-Sp, in agreement with the experimental observations.

Controlling Chemical Reactions by Short, Intense Mid-Infrared Laser Pulses: Comparison of Linear and Circularly Polarized Light in Simulations of ClCHO+ Fragmentation

Enhanced mode selective fragmentation of oriented ClCHO(+) → Cl + HCO(+), H + ClCO(+), HCl(+) + CO with linear polarized intense mid-IR pulses was demonstrated in our previous computational study ( J. Phys. Chem. Lett. 2012 , 3 , 2541 ). Simulations of angle-dependent strong field ionization of ClCHO indicate the ionization rate in the molecular plane is nearly twice as large as perpendicular to the plane, suggesting a degree of planar alignment can be obtained experimentally for ClCHO(+), starting from neutral molecules. Classical trajectory calculations with a 4 cycle 7 μm laser pulse (peak intensity of 1.26 × 10(14) W/cm(2)) show that circularly polarized light with the electric field in the plane of the molecule deposits more energy and yields larger branching ratios for higher energy fragmentation channels than linearly polarized light with the same maximum field strength. These results suggest circularly polarized mid-IR pulses can not only achieve control on reactions but also provide an experimentally accessible implementation.

Molecular Dynamics of Methylamine, Methanol, and Methyl Fluoride Cations in Intense 7 Micron Laser Fields

Fragmentation and isomerization of methylamine (CH3NH2(+)), methanol (CH3OH(+)), and methyl fluoride (CH3F(+)) cations by short, intense laser pulses have been studied by ab initio classical trajectory calculations. Born-Oppenheimer molecular dynamics (BOMD) on the ground-state potential energy surface were calculated with the CAM-B3LYP/6-31G(d,p) level of theory for the cations in a four-cycle laser pulse with a wavelengths of 7 μm and intensities of 0.88 × 10(14) and 1.7 × 10(14) W/cm(2). The most abundant reaction path was CH2X(+) + H (63-100%), with the second most favorable path being HCX(+) + H2 (0-33%), followed by isomerization to CH2XH(+) (0-8%). C-X cleavage after isomerization was observed only in methyl fluoride. Compared to random orientation, CH3X(+) with the C-X aligned with the laser polarization gained energy nearly twice as much from laser fields. The percentage of CH3(+) + X dissociation increased when the C-X bond was aligned with the laser field. Alignment also increased the branching ratio for H2 elimination in CH3NH2(+) and CH3OH(+) and for isomerization in CH3OH(+).