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P R LeBreton

Publications and source records attributed to P R LeBreton.

15 recordsLinked to original sources
PubMed1998

Conduction-band-edge ionization thresholds of DNA components in aqueous solution.

Numerous investigations have focused on DNA damage induced by ionizing radiation; however, photoionization threshold energies of nucleic acid components in aqueous solution are not known. Herein, data from gas-phase photoelectron experiments have been combined with results from self-consistent field and post-self-consistent field molecular orbital calculations and with theoretical Gibbs free energies of hydration to describe aqueous ionization energies of 2'-deoxythymidine 5'-phosphate (5'-dTMP-) and 2'-deoxycytidine 5'-phosphate (5'-dCMP-). For the test molecules, indole and tryptophan, this approach yields aqueous ionization energies (4.46 and 4.58 eV, respectively) in agreement with experimental values (4. 35 and 4.45 eV). When uridine and 2'-deoxythymidine ionization energies are evaluated, the results agree with recent data from 193-nm laser measurements indicating that uridine ionization occurs via a one-photon event. For 5'-dCMP- and 5'-dTMP-, a comparison of aqueous ionization energies with gas-phase ionization potentials (IPs) indicates that hydration alters the relative energies of ionization events. In the gas phase, phosphate vertical IPs are approximately 1.3 eV smaller than base IPs. In aqueous solution, the base and phosphate ionization energies are more similar, and only differ by approximately 0.5 eV. For 5'-dCMP- and 5'-dTMP-, the increased favorableness of base ionization, which accompanies hydration, is consistent with experimental data indicating that, at 77 K in aqueous perchlorate glasses, the primary photoionization pathway involves base ionization followed by deprotonation.

Chemical Phenomena↗
PubMed1996

Influence of Na+ on DNA reactions with aromatic epoxides and diol epoxides: evidence that DNA catalyzes the formation of benzo[a]pyrene and benz[a]anthracene adducts at intercalation sites.

Reactions of the benzo[a]pyrene (BP) and benz[a]anthracene (BA) metabolites, (+/-)-trans-7 8-dihydroxy-anti-9, 10-epoxy-7, 8, 9, 10-tetrahydro-BP (BPDE), (+/-)-trans-3, 4-dihydroxy-anti- 1,2-epoxy-1,2,3,4-tetrahydro-BA (BADE), (+/-)-BP-4,5-oxide (BPO), and (+/-)-BA-5, 6-oxide (BAO), were examined under pseudo-first-order conditions at varying Na+ (2.0-100 Mm) and native calf thymus DNA (ctDNA) concentrations. In 0.2 mM ctDNA and 2.0 mM Na+, at a pH of 7.3 most BPDE, BADE, BPO, and BAO (87-95%) undergo DNA catalyzed hydrolysis or rearrangement. For BPDE and BPO, overall, pseudo-first-order rate constants, k, in 2.0 mM Na+ and 0.2 mM ctDNA are 21-72 times larger than values obtained without DNA. For BADE and BAO, the rate constants are less strongly influenced by DNA; k values in 0.2 mM ctDNA are only 9-12 times larger than values obtained without DNA. Kinetic data for BPDE, BPO, BADE, and BAO and DNA intercalation association constants (KA) for BP and BA diols which are model compounds indicate that KA values for BPDE and BPO in 2.0 mM Na+ are 6.6-59 times larger than those of BADE and BAO. The greater DNA enhancement of rate constants for BPDE and BPO, versus BADE and BAO, correlates with the larger KA values of the BP metabolites. DNA adducts, which account for less than 10% of the yields, also form. For BPDE in 0.20 mM ctDNA, k decreases 5.1 times as the Na+ concentration increases from 2.0 to 100 mM. Nevertheless, the DNA adduct level remains constant over the range of Na+ concentrations examined. These results provide evidence that, for BPDE in 0.20 mM DNA and 2.0 mM Na+, ctDNA adduct formation follows a mechanism which is similar to that for DNA catalyzed hydrolysis. The pseudo-first-order rate constant for adduct formation, kAd, given approximately by kAd approximately equal to (kcat,AdKA[DNA])/(1 + KA[DNA]), where kcat,Ad is a catalytic rate constant. for BADE, BPO, and BAO, the influence of varying DNA and Na+ concentrations on k values is similar to that for BPDE, and provides evidence that the formation of adducts follows the same rate law.

Benz(a)Anthracenes↗
PubMed1995

HPLC preparation of highly purified single-stranded M13 DNA.

Closed-circular, single-stranded viral DNAs are widely employed in DNA cloning and sequencing experiments. Because of their well-defined structure and sequence, closed-circular, single-stranded DNAs have also been used for ligand binding experiments and light scattering measurements. However, there is a high molecular weight impurity observed in light scattering experiments, which sometimes contaminates single-stranded DNA purified from phage that has been precipitated in polyethylene glycol, average molecular weight 8000, and purified by standard phenol-chloroform extraction. Three methods have been examined that remove this impurity from closed-circular, single-stranded M13mp19 DNA (SS M13 DNA). One employs a commercial peparation. This procedure yields pure but degraded SS M13 DNA, as shown by light scattering measurements and HPLC. Another employs a Whatman DE52 (diethylamino cellulose) column. This procedure yields intact DNA, but in poor yield (less than 20% of that obtained by phenol-chloroform extraction). The last was the most successful. This employs HPLC with a Waters AP-1 column with DEAE 8HR bedding. This procedure, which provides DNA in high yield (80%-90% column recovery) with an intact structure, is an efficient method for the isolation of high-purity, closed-circular, single-stranded viral DNA suitable for physical investigations and ligand binding measurements.

Artifacts↗
PubMed1994

UV photoelectron and ab initio quantum mechanical characterization of valence electrons in Na(+)-water-2'-deoxyguanosine 5'-phosphate clusters: electronic influences on DNA alkylation by methylating and ethylating carcinogens.

UV photoelectron data for 1,9-dimethylguanine, 3-hydroxytetrahydrofuran, and water, and results from ab initio self-consistent field (SCF) and post-SCF molecular orbital calculations were employed to describe valence electrons in clusters of 2'-deoxyguanosine 5'-phosphate (5'-dGMP-) with four water molecules and a phosphate-bound sodium ion. Two clusters (A and B) were examined. In A, Na+ is coordinated to 5'-dGMP-. In B, Na+ and 5'-dGMP- are separated by water. In 5'-dGMP- clusters, the nucleotide valence ionization potentials (IPs) are different from those previously reported for isolated 5'-dGMP-. The smallest IP in isolated 5'-dGMP- (4.6 eV) arises from the phosphate group; the smallest IPs in A (8.2 eV) and B (7.9 eV) arise from the base. In the clusters, the IPs associated with the seven upper occupied base orbitals differ from corresponding IPs in 1,9-dimethylguanine by less than 0.4 eV. In A and B, the smaller IP of the base, compared with the phosphate group, is consistent with reactivity data indicating that DNA and RNA are subject to electrophilic SN2 attack by carcinogens such as N-methyl-N-nitrosourea, dimethyl and diethyl sulfate, and methyl and ethyl methanesulfonate, in which more than 75% of nucleotide alkylation occurs at the bases.

Alkylating Agents↗
PubMed1992

UV photoelectron and theoretical characterization of 2'-deoxyguanosine-5'-phosphate valence electronic properties: changes in structure associated with the B to Z-DNA conformational transition.

He(I) UV photoelectron spectroscopy and ab initio SCF molecular orbital calculations with the 4-31G basis set have been employed to characterize the valence electronic structures of 2'-deoxyguanosine-5'-phosphate (5'-dGMP-). In 5'-dGMP-, the electron distributions of the upper occupied orbitals are localized and similar to those appearing in 1,9-dimethylguanine (1), 3-hydroxytetrahydrofuran (2) and CH3HPO4- (3). Theoretical ionization potentials (IP's) of 5'-dGMP- (4) have been obtained by applying Koopmans' Theorem to the 4-31G SCF results. The IP's of seven orbitals in the base and sugar groups in 4, predicted from the 4-31G SCF calculations, have been individually corrected by comparison to results from 4-31G SCF calculations on neutral 5'-dGMP, and to Hel photoelectron spectra of the model compounds, 1 and 2. The IP's of six of the highest occupied orbitals of the phosphate group in 4 and in the model anion 3, predicted from 4-31G SCF calculations, have been corrected by comparing 4-31G SCF results for PO2- to theoretical IP's obtained from second-order Møller-Plesset perturbation calculations on PO2-. For 4 in the conformation occurring in B-DNA, the first IP's associated with the phosphate, base, and sugar groups occur at 5.1, 5.6 and 6.6 eV, respectively. A comparison of the valence electronic structures of 4 in geometries associated with the B and Z-DNA conformations indicates that in B-DNA the base and sugar orbitals have lower IP's than in Z-DNA, while the phosphate orbitals have higher IP's.

DNA↗
PubMed1990

Evidence for nonintercalative complexes formed from the reversible binding of benzo[a]pyrene metabolites to closed-circular, single-stranded M13mp19 DNA.

The fluorescence excitation spectrum of complexes formed from the reversible binding of the proximate carcinogen, trans-7,8-dihydroxy-7,8-dihydro-benzo[a]pyrene (BP78D) to closed-circular, single-stranded, viral M13mp19 DNA (SS M13 DNA) exhibits a red-shift of 5 nm compared to the spectrum of BP78D measured without DNA or with native, calf thymus DNA. In SS M13 DNA which is 0.10 mM in PO4-, the fluorescence intensity of BP78D is 2.3 times smaller than the intensity measured without DNA; however, the fluorescence lifetime (42.7 nsec) of BP78D with SS M13 DNA is 1.7-1.8 times larger than the lifetimes of BP78D measured without DNA or with calf thymus DNA. These results are consistent with the conclusion that, in addition to binding sites which cause fluorescence quenching, SS M13 DNA contains sites which permit formation of BP78D inclusion complexes that have weaker interactions with nucleotide bases than those occurring in intercalated complexes. The association constant (1.45 +/- 0.01 x 10(5) M-1) for the binding of BP78D to SS M13 DNA is more than 9.0 times larger than that for binding to calf thymus DNA. It is 7.1 times larger than that for the binding of the less genotoxic metabolite, trans-4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene (BP45D) to SS M13 DNA. UV Photoelectron data and results from ab initio molecular orbital calculations suggest that a difference in polarizability contributes to the greater SS M13 DNA binding of BP78D compared to that of BP45D.

Animals↗
PubMed1988

Influences of 7-alkyl substitution on the reversible binding of the proximate carcinogen trans-3,4-dihydroxy-3,4-dihydrobenz[a]anthracene to DNA.

The effects of 7-alkyl substitution on the reversible intercalation of the proximate carcinogen trans-3,4-dihydroxy-3,4-dihydrobenz[a]anthracene (BAD) to calf thymus DNA have been examined using time-resolved fluorescence spectroscopy. The results indicate that in 10(-3) M sodium cacodylate the binding constant of BAD is 1.8 x 10(3) M-1. 7-Ethyl substitution decreases the binding constant 1.6 times, while 7-methyl substitution increases the binding constant 1.7 times. UV Photoelectron data and results from ab initio molecular orbital calculations suggest that an increase in polarizability contributes to the increased binding accompanying methyl substitution. The decreased binding accompanying ethyl substitution arises from steric inhibition. The physical binding data correlates with the decrease in carcinogenic activity which occurs with 7-ethyl substitution of benz[a]anthracene metabolites.

Alkylation↗
PubMed1988

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.

Chemical Phenomena↗
PubMed1985

A comparison of the DNA intercalative binding of bay versus K region metabolites of benzo[a]pyrene.

The DNA intercalating properties of trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (1) and of trans-4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene (2) have been compared in UV absorption and in fluorescence emission and fluorescence lifetime studies. Molecules 1 and 2 represent steric models of the two epoxide containing metabolites of benzo[a]pyrene, trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and benzo[a]pyrene-4,5-oxide. The former of these metabolites is a highly carcinogenic bay region metabolite, the latter is a much less carcinogenic K region metabolite. The association constant for intercalation for model 1 is 5,226 M-1. This is more than 2.7 times greater than that for molecule 2. These results taken together with results form previous studies of bay and K region metabolite models of benz[a]anthracene suggest that intercalation is important to the overall carcinogenic activity of polycyclic aromatic hydrocarbons.

Benzo(a)pyrene↗
PubMed1984

Intercalative DNA binding of model compounds derived from metabolites of 7,12-dimethylbenz[a]anthracene.

The DNA binding of nonreactive model compounds of metabolites of 7,12-dimethylbenz[a]-anthracene (DMBA)1 was studied in fluorescence quenching and fluorescence lifetime experiments. The model compounds examined were DMA and 8,9,10,11-tetrahydro-BA. DMA is a pi electron model of a highly carcinogenic bay region epoxide of DMBA, 8,9,10,11-tetrahydro-BA is a model compound of a less carcinogenic DMBA epoxide. The results indicate that the binding of DMA occurs primarily via intercalation. In 15% methanol the binding constant is 3.1 x 10(3) M-1. In 15% methanol and at DNA phosphate levels of 5.0 x 10(-4) M the intercalative binding of DMA is reduced by a factor of 6.2 when 5.0 x 10(-4) M Mg+2 is added. The DMA binding constant for intercalation is reduced by more than a factor of 4 when the methanol content of the solvent is increased from 0% to 20%. Finally DMA binding arising from pi interactions with the DNA bases is reduced more than 15 times when the DNA is denatured. For 8,9,10,11-tetrahydro-BA in 15% methanol the binding constant for intercalation is 6 times lower than that for DMA. These results along with previously reported binding data on other model compounds suggest that bay region metabolites of DMBA readily participate in physical pi stacking interactions with DNA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

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.

Benz(a)Anthracenes↗
PubMed1976

Ultraviolet photoelectron studies of biological purines: the valence electronic structure of adenine.

The UV photoelectron spectra of adenine, 9-methyladenine, and 6-methylaminopurine contain highly resolved bands arising from the six highest occupied molecular orbitals. The spectra have been analyzed using UV absorption data, photoelectron data from previous studies of heterocyclic compounds, and results from both semi-empirical and ab initio molecular orbital calculations. The analysis indicates that the first, third, and fifth photoelectron bands in adenine and the two methyl substituted derivatives arise from pi orbitals. The second, fourth, and sixth bands arise from nitrogen atom lone-pair orbitals. Compared to adenine, the six uppermost orbitals of 9-methyladenine and 6-methylaminopurine have lower ionization potentials. This destabilization of the valence electrons is expected to play an important role in causing the increase in base stacking forces observed in methyl substituted adenines.

2-Aminopurine↗
PubMedDate not supplied

Multiple fluorescence lifetimes for oligonucleotides containing single, site-specific modifications at guanine and adenine corresponding to trans addition of exocyclic amino groups to (+)-(7R,8S,9S,10R)- and (+)-(7S,8R,9R,10S) -7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.

Fluorescence decay profiles of four oligonucleotide duplexes, [table: see text] ((+)- and (-)-trans-1) and [table: see text] ((+)- and (-)-trans-2), in which an exocyclic amino group of deoxyadenosine (A*) or deoxyguanosine (G*) has been alkylated by trans opening at C-10 of the epoxide group of either the (+)-(R,S,S,R)- or (-)-(S,R,R,S)-enantiomer of (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE in which the benzylic 7-hydroxy group and the epoxide oxygen are trans), exhibit more than one fluorescence lifetime. Decay profiles of the oligomers, measured at 15 degrees C with excitation and emission wavelengths of 335 and 400 nm, respectively, have been analyzed using a triple-exponential decay law. Results for (+)- and (-)-trans-1 and -2 have been compared with results for the modified, single-stranded oligonucleotides ((+)- and (-)-trans-SS-1, and (+)- and (-)-trans-SS-2) and for the cis and trans opened products formed on alkylation at the 6-amino group of 2'-deoxyadenosine 5'-phosphate by (+)-(R,S,S,R)-BPDE ((+)-trans- and (+)-cis-A). The profiles of (+)-trans- and (+)-cis-A are well represented by single-exponential decay laws with lifetimes of 86 and 110 +/- 3 ns, respectively. For the single- and double-stranded oligomer adducts, which exhibit at least three fluorescence lifetimes, two of the lifetimes are short (0.5-14 +/- 1 ns) and one is long (35-59 +/- 3 ns). The fluorescence lifetimes and the amplitudes of the long-lived components in the decay profiles of the double-stranded oligomer adducts are generally smaller than those for the corresponding single-stranded adducts. The data provide evidence that the double-stranded oligomer adducts exist as multiple conformations. Previously reported NMR results suggest that the short lifetime fluorescence components are due to major adduct conformations in which the pyrenyl group is intercalated ((+)- and (-)-trans-1) or lies in the minor groove ((+)- and (-)-trans-2). The observation of long lifetime fluorescence species for the double-stranded oligomers is consistent with the presence of minor conformations (approximately 1-5%) in which the double-stranded oligomer either is locally denatured or is a mixture of locally denatured double-stranded conformations and equilibrium concentrations of single-stranded oligomers.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗