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Amino acid radicals are often involved as intermediates in biological processes, but are difficult to capture by experiment. Computational modeling can be employed to study the features of the spec ...

The intercalation and photobinding of 8-methoxypsoralen with thymine in DNA is studied by computational chemistry techniques. Photochemical [2+2] cycloadditions at the S-1 surface display barriers of approximately 20 kcal/mol. The lowest lying excited surface has a defined potential well at the ground state TS, enabling for efficient decay. Avoided crossings between the S-1 and S-2 surfaces are also observed, which may influence the photochemical reactivity. The further reactions leading to crosslink formation from furan monoadducts but not from pyrone ones are fully explained by the excitation energies of the monoadducts, whereas the predominance of furan over pyrone monoadduct formation is not explained looking at the excitation energy surfaces alone. (C) 2009 Elsevier B.V. All rights reserved.

DNA damages caused by a 5-hydroxy-5,6-dihydrothymine-6-yl radical (5-OHT-6yl) abstracting a C20 hydrogen from a neighboring sugar (inter-H abstraction) have been theoretically investigated using hybrid DFT in gas phase and in water solution. The inter-H abstraction was here shown to be comparable in energy (24 kcal mol 1) with the intra-H abstraction in which the 5-OHT-6yl abstracts a C20 hydrogen from its own sugar. The effect of a neutrally or a negatively charged phosphate group was also studied and the results show no significant impact on the activation energy of the hydrogen abstraction whereas base release and strand break reactions are affected.

5-Aminolevulinic acid (5ALA) is the key synthetic building block in protoporphyrin IX (PpIX), the heme chromophore in mitochondria. The addition of extracorporeal 5ALA and its alkyl ester derivativ ...

The intramolecular radical cross-link reactions of 8,5′-cyclo-purines and 6,5′-cyclo-pyrimidines have been studied using the DFT B3LYP formalism with 6-31+G(d,p) and 6-311++G(d,p) basis sets, and including CPCM bulk solvation effects. In aqueous solution, the largest free energy barrier is 11.1 kcal/mol for dT → 6,5′-cycloT and the smallest 9.4 kcal/mol for dA → 8,5′-cycloA . Partial radical transfer occurs from the deoxyribose moiety to the connected base upon the formation of the transition structures. The unpaired spin density of the products is mainly localized on N7 in the 8,5′-cyclo-purines and on C5 in the 6,5′-cyclo-pyrimidines. The reaction free energies range from −4.3 kcal/mol (dC → 6,5′-cycloC ) to −9.7 kcal/mol (dG → 8,5′-cycloG ).

The photoactivation of the plant photoreceptor phytochrome is governed by a red-light-induced C15- Z → C15- E isomerization of the tetrapyrrolic chromophore phytochromobilin. From the viewpoint of experimental studies, ambiguity prevails as to whether the photoactivation involves a proton transfer from the chromophore to the surrounding protein. Here, we report a theoretical study addressing the effect of phytochromobilin protonation state on its photoisomerization by means of quantum chemical calculations. It is found that neutral forms of the chromophore are much less likely to photoisomerize than the parent, protonated form – a finding which supports the view that phytochromobilin remains protonated during phytochrome photoactivation.

Non-enzymatic oxidation of NADH by a large number of different quinones has been explored both theoretically and experimentally. It is concluded that the smaller benzo- and naphtho-quinones are capable of oxidising NADH in aqueous solution, whereas the larger anthraquinone is not. The mechanisms of stepwise electron and proton transfers are explored, and ruled out in favour of direct hydride transfer. For menadione (2-methyl-1,4-naphthoquinone), no reaction is observed experimentally; theoretically we find that there is a very close balance between the energetic cost of hydride removal from NADH and the energy gain of formation of the menadione semiquinone radical anion.

The photo-oxidation reactions between lipid model nona-3,6(c,c)-diene and singlet molecular oxygen are investigated using density functional theory and polarized continuum models. Additions to both the 3- and 4-position of the lipid model (corresponding to the 9(13)- and 10(12)-positions of 9,12 lipid dienes such as linoleic acid) are explored. It is concluded that the modes of attack will lead to adduct intermediates which evolve either to dioxetane formation overcoming a significant energy barrier, or to the final LOOH products (hydro-peroxide bonded to either the 3- or 4-position), for which no transition barriers towards H-abstraction could be located. The computed energy surfaces are in close accord with results for the reactions between singlet oxygen and other unsaturated systems, and explain both the observed difference in product distribution in biological samples and, through the high energy barriers to addition of the initial reactants (15–20 kcal/mol), the low reactivity of singlet oxygen in biological membranes.

The structural origin of the bathochromic shift assumed by the electronic absorption spectrum of protein-bound astaxanthin, the carotenoid that upon binding to crustacyanin is responsible for the blue colouration of lobster shell, is investigated by means of quantum chemical methods. The calculations suggest that the bathochromic shift is largely due to one of the astaxanthin C4 keto groups being hydrogen-bonded to a histidine residue of the surrounding protein, and that the effect of this histidine is directly dependent on its protonation state. Out of the different methodologies (CIS, TD-DFT, and ZINDO/S) employed to calculate wavelengths of maximum absorption, the best agreement with experimental data is obtained using the semiempirical ZINDO/S method.

The gas phase and solution electron affinities and ionization potentials of uracil, thymine and a series of 5-halouracils ( 5XU, X=F, Cl, Br ) are investigated with B3LYP. Halogen substitution has a smaller effect on the IP than the EA of U . The EAs are calculated to increase according to T U 5FU 5ClU 5BrU . The calculated barriers for the dissociation of the resulting 5XU anions to X − plus uracil-centered radicals decrease along the series 5FU − > 5ClU − > 5BrU − . The calculated trends are consistent with suggestions that 5XUs enhance the sensitivity of deoxyribonucleic acid, DNA (ribonucleic acid, RNA) to ionizing radiation and that 5BrU leads to the greatest enhancement.

Density-functional theory (B3LYP functional) is used to investigate the ionization potentials and electron affinities of the DNA and RNA nucleotide bases. For the first time, anions lying lower in energy than the neutral species have been calculated for both thymine and uracil (i.e., positive adiabatic electron affinities). Additionally, the calculations show that anion formation leads to significant geometrical changes to the nucleobases. This is a very important finding as previous calculations have indicated that the anions are very similar in geometry to the neutral species and reported negative valence adiabatic electron affinities.

Several density functional methods are applied to calculate the hyperfine coupling constants and spin population distributions of sulfur-substituted and unsubstituted tyrosyl radical. The cysteine-substituted tyrosyl radical is found at the active site of the radical enzyme of galactose oxidase. The main conclusion is that the sulfur center only possesses a small amount of unpaired spin not sufficient to perturb the overall odd-alternant spin distribution in the tyrosyl radical. The original assignment of two hyperfine couplings, one from a tyrosine β-proton and one from H 5 , is clearly confirmed by calculated isotropic hyperfine coupling constants. The inclusion of solvent effects does not alter any of the conclusions.

Ab initio molecular orbital (MP2/6-311G(d,p) and CASPT2/ANO) and density functionl theory (DFT/IGLO-III) calculations have been applied to determine some basic properties of phenyl phosphinidenee (C 6 H 5 P). Geometrics, harmonic vibrational wavenumbers, singlet-triplet energy gaps, heats of formation and hyperfine splitting constants have been calculated. Phenylphosphinidene has a triplet 3 A 2 ground state lying 22±3 kcal/mol below the closed-shell singlet 1 A 1 state and some calculated properties are: heat of formation at 0 K ΔH 0 f,0 = 68 ± 5 kcal/mol, vertical ionization energy IE v = 10.6 ± 0.3 eV, electron affinity EA a = 0.89±03 eV, proton affinity PA = 140±5 kcal/mol and isotropic hyperfine splitting constant a( 31 P) = 66 ± 3 G . The open-shell singlet 1 A 2 state is a low-lying state having comparable energy with the 1 A 1 . The properties of C 6 H 5 P are similar to those of methylphosphinidene (CH 3 P). The singlet-triplet gap ( 1 A′– 3 A 2 ) in CH 3 P amounts to 26 ± 3 kcal/mol. Relative to the CH 3 P, the phneyl group has a small effect on the singlet state but seems to destabilize the triplet state and thereby reduce the singlet-triplet gap.

The interactions between an alkali metal atom (Li, Na, K) and acetylene/vinylidene are investigated by means of gradient corrected (‘PWP’) density functional theory. Particular emphasis is made on the determination of equilibrium geometries, energetics and atomic hyperfine structures of the MHCCH van der Waals addition complexes, and the MHCCH and MCCH2 charge-transfer complexes. The PWP optimized geometries are found to be similar to previous ab initio data, and the generated hyperfine structures are in excellent accord with experimental matrix isolation ESR data recorded at 4 K. In the charge transfer complex formation, the metal atoms are found to donate 0.6–0.8 electron from an excited p orbital to the antibonding CC π∗ orbital of the hydrocarbon fragment. The calculated trend in charge donation matches the order of increasing atomic s → p excitation energies, K < Li < Na. This is the first application of the present method to metal atom hyperfine structures, and the results are promising for future studies.

Density functional theory calculations of isotropic couplings of the atoms B to O are carried out with a variety of functional forms and basis sets. It is shown that the atomic isotropic coupling constants are very dependent on functional form, auxiliary basis set and orbital set. The calculations on the molecular systems NH 2 and H + 3 show less dependence for isotropic couplings and almost independence for anisotropic couplings. It is found that the combination of Perdew and Wang's non-local exchange functional and Perdew's correlation correction functional with a [7s, 6p, 2d]/(5, 2; 5, 2) orbital/auxiliary basis set gives results in semiquantitative agreement with experiment and MRSDCI calculations.

The influence of up to six Ne atoms on the isotropic hyperfine (hf) coupling constants of the hydrogen atoms in CH+4 is investigated using density functional theory. It is found that at very short NeH distances (R = 1.8 A), the hf structure is strongly affected, whereas at the more realistic van der Waals distance (R ≈ 2.5 A), the methane radical experiences a very weak field from the surrounding Ne atoms. At larger distances, the effects of the Ne matrix are negligible. It is furthermore found that at small R, the changes in aiso (H) are strongly dependent on the relative positions of the Ne atoms.

Modelling the behavior of 5-aminolevulinic acid and its alkyl esters in a lipid bilayer (vol 463, pg 178, 2008)