Role of hydrophobic effects in the reaction of a polynuclear aromatic diol epoxide with oligodeoxynucleotides in aqueous solutions

Nikolai Pirogov, Vladimir Shafirovich, Alexander Kolbanovskiy, Kyril Solntsev, Scott A. Courtney, Shantu Amin, Nicholas E. Geacintov

Research output: Contribution to journalArticle

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Abstract

The need for large-scale direct synthesis of stereochemically defined and site-specific benzo[a]pyrenediol epoxide-oligodeoxyribonucleotide adducts for detailed NMR and other biochemical and physicochemical studies has necessitated a better understanding of variables that lead to an enhancement of the reaction yields. It is shown that, in aqueous solution, the formation of noncovalent hydrophobic complexes between 7r,8t-dihydroxy-9t,10t-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and the single-stranded oligonucleotide 5'-d(CCATCGCTACC) precedes the covalent binding reaction of BPDE with the single deoxyguanosine residue. The yield of covalent reaction products (involving reaction of BPDE at the C10 position with the exocyclic amino group of the dG residue) increases with increasing DNA concentration and tends toward saturation at oligonucleotide single-strand concentrations above ~3 mM. The addition of NaCl (0.3 M) also tends to enhance the adduct reaction yields. However, organic solvents such as tetrahydrofuran in the reaction mixtures (10-40%) decrease the stabilities of the noncovalent complexes, which in turn leads to reductions in the yields of covalent BPDE- dG oligonucleotide adducts. The efficiencies of formation of hydrophobic complexes were probed by fluorescence and UV absorption techniques using the BPDE tetrol hydrolysis product 7,8,9,10-tetrahydroxytetrahydrobenzo[a]pyrene as a model system.

Original languageEnglish (US)
Pages (from-to)381-388
Number of pages8
JournalChemical Research in Toxicology
Volume11
Issue number4
DOIs
StatePublished - May 11 1998

Fingerprint

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
Oligodeoxyribonucleotides
Epoxy Compounds
Oligonucleotides
Deoxyguanosine
Reaction products
Organic solvents
Hydrolysis
Fluorescence
Nuclear magnetic resonance
DNA

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Pirogov, Nikolai ; Shafirovich, Vladimir ; Kolbanovskiy, Alexander ; Solntsev, Kyril ; Courtney, Scott A. ; Amin, Shantu ; Geacintov, Nicholas E. / Role of hydrophobic effects in the reaction of a polynuclear aromatic diol epoxide with oligodeoxynucleotides in aqueous solutions. In: Chemical Research in Toxicology. 1998 ; Vol. 11, No. 4. pp. 381-388.
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abstract = "The need for large-scale direct synthesis of stereochemically defined and site-specific benzo[a]pyrenediol epoxide-oligodeoxyribonucleotide adducts for detailed NMR and other biochemical and physicochemical studies has necessitated a better understanding of variables that lead to an enhancement of the reaction yields. It is shown that, in aqueous solution, the formation of noncovalent hydrophobic complexes between 7r,8t-dihydroxy-9t,10t-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and the single-stranded oligonucleotide 5'-d(CCATCGCTACC) precedes the covalent binding reaction of BPDE with the single deoxyguanosine residue. The yield of covalent reaction products (involving reaction of BPDE at the C10 position with the exocyclic amino group of the dG residue) increases with increasing DNA concentration and tends toward saturation at oligonucleotide single-strand concentrations above ~3 mM. The addition of NaCl (0.3 M) also tends to enhance the adduct reaction yields. However, organic solvents such as tetrahydrofuran in the reaction mixtures (10-40{\%}) decrease the stabilities of the noncovalent complexes, which in turn leads to reductions in the yields of covalent BPDE- dG oligonucleotide adducts. The efficiencies of formation of hydrophobic complexes were probed by fluorescence and UV absorption techniques using the BPDE tetrol hydrolysis product 7,8,9,10-tetrahydroxytetrahydrobenzo[a]pyrene as a model system.",
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Role of hydrophobic effects in the reaction of a polynuclear aromatic diol epoxide with oligodeoxynucleotides in aqueous solutions. / Pirogov, Nikolai; Shafirovich, Vladimir; Kolbanovskiy, Alexander; Solntsev, Kyril; Courtney, Scott A.; Amin, Shantu; Geacintov, Nicholas E.

In: Chemical Research in Toxicology, Vol. 11, No. 4, 11.05.1998, p. 381-388.

Research output: Contribution to journalArticle

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T1 - Role of hydrophobic effects in the reaction of a polynuclear aromatic diol epoxide with oligodeoxynucleotides in aqueous solutions

AU - Pirogov, Nikolai

AU - Shafirovich, Vladimir

AU - Kolbanovskiy, Alexander

AU - Solntsev, Kyril

AU - Courtney, Scott A.

AU - Amin, Shantu

AU - Geacintov, Nicholas E.

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N2 - The need for large-scale direct synthesis of stereochemically defined and site-specific benzo[a]pyrenediol epoxide-oligodeoxyribonucleotide adducts for detailed NMR and other biochemical and physicochemical studies has necessitated a better understanding of variables that lead to an enhancement of the reaction yields. It is shown that, in aqueous solution, the formation of noncovalent hydrophobic complexes between 7r,8t-dihydroxy-9t,10t-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and the single-stranded oligonucleotide 5'-d(CCATCGCTACC) precedes the covalent binding reaction of BPDE with the single deoxyguanosine residue. The yield of covalent reaction products (involving reaction of BPDE at the C10 position with the exocyclic amino group of the dG residue) increases with increasing DNA concentration and tends toward saturation at oligonucleotide single-strand concentrations above ~3 mM. The addition of NaCl (0.3 M) also tends to enhance the adduct reaction yields. However, organic solvents such as tetrahydrofuran in the reaction mixtures (10-40%) decrease the stabilities of the noncovalent complexes, which in turn leads to reductions in the yields of covalent BPDE- dG oligonucleotide adducts. The efficiencies of formation of hydrophobic complexes were probed by fluorescence and UV absorption techniques using the BPDE tetrol hydrolysis product 7,8,9,10-tetrahydroxytetrahydrobenzo[a]pyrene as a model system.

AB - The need for large-scale direct synthesis of stereochemically defined and site-specific benzo[a]pyrenediol epoxide-oligodeoxyribonucleotide adducts for detailed NMR and other biochemical and physicochemical studies has necessitated a better understanding of variables that lead to an enhancement of the reaction yields. It is shown that, in aqueous solution, the formation of noncovalent hydrophobic complexes between 7r,8t-dihydroxy-9t,10t-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and the single-stranded oligonucleotide 5'-d(CCATCGCTACC) precedes the covalent binding reaction of BPDE with the single deoxyguanosine residue. The yield of covalent reaction products (involving reaction of BPDE at the C10 position with the exocyclic amino group of the dG residue) increases with increasing DNA concentration and tends toward saturation at oligonucleotide single-strand concentrations above ~3 mM. The addition of NaCl (0.3 M) also tends to enhance the adduct reaction yields. However, organic solvents such as tetrahydrofuran in the reaction mixtures (10-40%) decrease the stabilities of the noncovalent complexes, which in turn leads to reductions in the yields of covalent BPDE- dG oligonucleotide adducts. The efficiencies of formation of hydrophobic complexes were probed by fluorescence and UV absorption techniques using the BPDE tetrol hydrolysis product 7,8,9,10-tetrahydroxytetrahydrobenzo[a]pyrene as a model system.

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