Pierre R. LeBreton

UV photoelectron studies of biological pyrimidines: the valence electronic structure of methyl substituted uracils

Abstract UV photoelectron spectroscopy and INDO molecular orbital calculations have been employed to investigate the electronic structure of several methyl substituted uracils. The results indicate that the ionization potential of uracils is most sensitive to perturbation at the 1 and 5 positions. Substitution occurs in both of these positions in biological systems. It is also found that the large (0.4 eV) differences in the ionization potential of uracil and thymine is conserved in the nucleoside models 1-methyluracil and 1-methylthymine.

Tri-s-triazine: synthesis, chemical behavior, and spectroscopic and theoretical probes of valence orbital structure

Synthese du tri-s-triazine, et determination de sa structure par diffraction RX; etude de ses proprietes chimiques, spectroscopiques et physiques. On utilise la spectrometrie photoelectronique ainsi que des calculs ab initio et HAM3

Uv photoelectron studies of biological pyrimidines: The electronic structure of uracil☆

Abstract The photoelectron spectrum of uracil has been measured in the gas phase. A qualitative interpretation of the spectrum indicates that the first and third highest occupied orbitals in uracil are π orbitals, while the second and fourth highest orbitals are lone-pair orbitals associated with oxygen atoms. This ordering is consistent with that predicted by CNDO and INDO molecular orbital calculations.

Activation barriers for DNA alkylation by carcinogenic methane diazonium ions

Methylation reactions of the DNA bases with the methane diazonium ion, which is the reactive intermediate formed from several carcinogenic methylating agents, were examined. The SN2 transition states of the methylation reactions at N7, N3, and O6 of guanine; N7, N3, and N1 of adenine; N3 and O2 of cytosine; and O2 and O4 of thymine were calculated using the B3LYP density functional method. Solvation effects were examined using the conductor‐like polarizable continuum method and the combined discrete/SCRF method. The transition states for reactions at guanine N3, adenine N7, and adenine N1 are influenced by steric interactions between the methane diazonium ion and exocyclic amino groups. Both in the gas phase and in aqueous solution, the methylation reactions at N atoms have transition states that are looser, and generally occur earlier along the reaction pathways than reactions at O atoms. The forming bonds in the transition states in water are 0.03 to 0.13 Å shorter than those observed in the gas phase, and the activation energies are 13 to 35 kcal/mol higher. The combined discrete/SCRF solvation energy calculations using base‐water complexes with three water molecules yield base solvation energies that are larger than those obtained from the CPCM continuum method, especially for cytosine. Reactivities calculated using barriers obtained with the discrete/SCRF method are consistent with the experimentally observed high reactivity at N7 of guanine.

A comparison of the intercalative binding of nonreactive benzohpyrene metabolites and metabolite model compounds to dna

The reversible DNA physical binding of a series of non-reactive metabolites and metabolite model compounds derived from benzo[a]pyrene (BP) has been examined in UV absorption and in fluorescence emission and fluorescence lifetime studies. Members of this series have steric and pi electronic properties similar to the highly carcinogenic metabolite trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and the less potent metabolite 4,5-epoxy-4,5-dihydrobenzo(a)pyrene (4,5-BPE). The molecules examined are trans-7,8-dihydroxy-7,8-dihydrobenzo[a]-pyrene (7,8-di(OH)H2BP), 7,8,9,10-tetrahydroxytetrahydrobenzo[a]pyrene (tetrol) 7,8,9,10-tetrahydrobenzo[a]pyrene (7,8,9,10-H4BP), pyrene, trans-4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene (4,5-di(OH)H2BP) and 4,5-dihydrobenzo[a]pyrene (4,5-H2BP). In 15% methanol at 23 degrees C the intercalation binding constants of the molecules studied lie in the range 0.79-6.1 X 10(3) M-1. Of all the molecules examined the proximate carcinogen 7,8-di(OH)-H2BP is the best intercalating agent. The proximate carcinogen has a binding constant which in UV absorption studies is found to be 2.8-6.0 times greater than that of the other hydroxylated metabolites. Intercalation is the major mode of binding for 7,8-di(OH)H2BP and accounts for more than 95% of the total binding. Details concerning the specific role of physical bonding in BP carcinogenesis remain to be elucidated. However, the present studies demonstrate that the reversible binding constants for BP metabolites are of the same magnitude as reversible binding constants which arise from naturally occurring base-base hydrogen bonding and pi stacking interactions in DNA. Furthermore, previous autoradiographic studies indicate that in human skin fibroblasts incubated in BP, pooling of the unmetabolized hydrocarbons occurs at the nucleus. The high affinity of 7,8-di(OH)H2BP for DNA may play a role in similarly elevating in vivo nuclear concentrations of the non-reactive proximate carcinogen.

Fluorescence and photoelectron studies of the intercalative binding of benz(a)anthracene metabolite models to DNA.

DNA binding of nonreactive metabolite models derived from benz(a)anthracene was studied. The molecules investigated include 1,2,3,4-tetrahydrobenz(a)anthracene (1), 5,6-dihydrobenz(a)anthracene (2), and 8,9,10,11-tetrahydrobenz(a)anthracene (3), as well as anthracene and phenanthrene. Measurements of the effects of DNA binding upon fluorescence intensities and fluorescence lifetimes indicate that molecules 1 and 3 (KA = 1.5 - 2.5 x 10(3) M-1) bind more strongly to native DNA than does molecule 2 (KA congruent to 0.5 x 10(3) M-1). Furthermore, molecules 1 and 3 bind to DNA much more effectively than do the two less sterically hindered pi electron metabolite models, anthracene and phenanthrene. Photoelectron data suggests that the enhanced binding of molecules 1 and 3 is due to increases in polarizability. Experiments carried out with denatured DNA indicate that the binding of molecule 1 entails the greatest intercalation.

UV Photoelectron Spectroscopy and Ab Initio Characterization of Valence Orbital Structures and Conformations of Neutral Phosphate Esters

The HeI UV photoelectron spectrum of trimethyl phosphate (TMP) has been measured and interpreted with the aid of SCF molecular orbital calculations carried out with STO-3G, STO-3G* and 4-31G basis functions. The photoelectron spectrum of TMP is more accurately reproduced by results from 4-31G calculations than by results from STO-3G or STO-3G* calculations. However, all three basis sets yield results which predict the same assignment of the photoelectron spectrum. Results at the 4-31G level indicate that whether calculations are based on crystallographic bond angles and bond lengths or on STO-3G optimized geometries has little effect on the energetic ordering of the upper occupied orbitals. The energetic ordering of orbitals is also found to be only weakly dependent upon the torsional angle phi, describing rotation of ester groups about P-O bonds and upon the torsional angle psi, describing rotation of methyl groups about C-O bonds. For trimethyl phosphate, with C3 symmetry, the vertical ionization potentials of the upper occupied orbitals are 10.81 eV (8e), 11.4 eV (9a), 11.93 eV (7e), 12.6-12.9 eV (8a and 6e), 14.4 eV (7a) and 15.0-16.0 eV (5e and 6a). Calculations at the 4-31G level indicate that many of the highest occupied orbitals in neutral dimethyl phosphate and methyl phosphate have energies and electron distributions similar to orbitals in TMP. For TMP, a search for optimized values of phi and psi has been carried out at the STO-3G*level. In agreement with previous NMR studies and with classical potential calculations, the STO-3G* results indicate that both the gauche (phi = 53.1 degrees) and anticlinal (phi = 141.9 degrees) conformations are thermally accessible. Also in agreement with the classical potential calculations, the STO-3G* results predict that in the all gauche conformation energy is minimized when the methyl groups assume a staggered geometry (psi = 60 degrees to 80 degrees) and that an energy maximum occurs for an eclipsed geometry (phi = 0 degrees to 20 degrees). A study of the dependence of optimized values of O-P-O ester bond angles on the torsional angles, phi, was carried out at the STO-3G, STO-3G* and 4-31G levels. The results demonstrate that for C3 symmetry, the coupling of O-P-O angles to phi is influence by repulsive steric interactions.

Through space interactions of double bonds by photoelectron spectroscopy

Steric effects between double bonds and remote polar substituents, previously manifested in nuclear magnetic resonance (NMR) spectra, are also evident in the ultraviolet photoelectron spectra (UPS). An ether functionality was introduced at the 3-axial position of exo-methylenecyclohexane by means of acetal groups (dimethyl and ethylene). The 3-axial ether group destabilizes the 7r orbital on the double bond by 0.1-0.2 eV by a through space interaction (the 3-equatorial ether group by itself has little or no effect). This interaction apparently is responsible for the decreased proportion of 3-axial methoxyl observed by NMR spectroscopy. In contrast, 4-axial ether functionalities in cyclohexene show a slight stabilizing of the n orbital by through bond electron withdrawal. These results also agree with the NMR observations, since the endocyclic double bond of cyclohexene permits a much larger proportion of 4-axial methoxyl. Ab initio calculations support the observations by paralleling the observed r-orbital energies and by providing electron densities. Whereas 3-axial methoxyl clearly polarizes the double bond in methylenecyclohexane, 4-axial methoxyl has little or no effect on the electron densities of cyclohexene, even though methoxyl is closer to the endocyclic than to the exocyclic double bond. The NMR, UPS, and ab initio results provide an initial understanding of the three dimensionality of the n-electron steric effects. Nuclear magnetic resonance studies have shown that the double bond interacts in a complex fashion with remote polar substituents.,-* A 3-axial substituent in a six-membered ring is more repulsive with an exocyclic double bond than with a saturated CH2 group at the same position (eq I).,., Thus in a nonpolar solvent

Ultraviolet photoelectron studies of methyl substituted crysenes

Abstract Ultraviolet photoelectron spectroscopy and CNDO S3 molecular orbital calculations have been employed to investigate the ground-state electronic structure of all six of the monomethyl-substituted crysenes including the highly carcinogenic 5-methylcrysene. The photoelectron results yield ionization potentials for the five highest occupied π orbitals in each of these molecules. The data has been employed to test whether the radical cation theory of hydrocarbon carcinogenicity applies to methyl substituted crysenes.

Model transition states for methane diazonium ion methylation of guanine runs in oligomeric DNA

The DNA reaction pattern of the methane diazonium ion, which is the reactive intermediate formed from several carcinogenic methylating agents, was examined at N7 and O6 sites in guanine runs occurring in oligonucleotides and model oligonucleotides. Density functional B3LYP/6‐31G*, and SCF 3‐21G and STO‐3G energies of model transition states were calculated in the gas phase and in the CPCM reaction field. For nucleotides containing two, three, and four stacked guanines with counterions in the gas phase, O6 reactivity is greater than N7 reactivity. In the reaction field, N7 reactivity is 9.0 to 9.8 times greater than O6 reactivity. For a double‐stranded oligonucleotide containing two stacked guanines with counterions in the reaction field, the N7 and O6 reactivities of the 3′‐guanine are 3.9 times greater than the corresponding sites in the 5′‐guanine. For double‐stranded oligonucleotides with three or four stacked guanines and counterions, the reactivities of the interior guanines are higher than corresponding reactivities of guanines at the ends. These reaction patterns agree with most of the available experimental data. Activation energy decomposition analysis for gas‐phase reactions in a double‐stranded dinucleotide containing two stacked guanines with counterions indicates that selectivity at O6 is almost entirely due to electrostatic forces. Selectivity at N7 also has a large electrostatic interaction. However, the orbital interaction also contributes significantly to the gas‐phase selectivity, accounting for 32% of the total interaction energy difference between the 3′‐ and 5′‐guanine reactions. In aqueous solution, the relative orbital contribution to N7 selectivity is likely to be larger.