Vladimir Shafirovich Research Professor of Chemistry M.S., Moscow State University; Ph.D., Institute of Chemical Physics, Chernogolovka; D. Sc., Institute of Chemical Physics, Chernogolovka Email: vs5@nyu.edu Phone:  212-998-8456

Areas of Research/Interest: Biophysical Chemistry: kinetic laser spectroscopy studies of oxidative DNA damage induced by reactive oxygen and nitrogen species; biological impact of oxidatively modified DNA bases; chemistry of nitroxyl and its anion in aqueous solutions

Research Description: Our research is focused on reactions of genotoxic reactive oxygen and nitrogen species with DNA that contribute to the etiology of cancer by poorly defined pathways. In DNA the attack of these species is focused on guanine, the most easily oxidizable nucleic acid base. Our central hypothesis is that neutral guanine radicals derived from one electron oxidation of guanine by highly reactive oxyl radicals are key intermediates for the generation of genotoxic oxidative modifications in cellular DNA. Another focus of our research is the aqueous chemistry of nitroxyl (HNO). In collaboration with Dr. Sergei Lymar (Brookhaven National Laboratory) we showed that the ground state of nitroxyl anion is a triplet, and that HNO in its singlet ground state is a much weaker acid, pKa ~ 11.4, than previously believed. According to this novel concept, a small neutral molecule HNO should be able to penetrate through biological membranes and, therefore, its role in biology and medicine may be important.

Select Publications:

Lymar, S. V., Shafirovich, V. Photoinduced Release of Nitroxyl and Nitric Oxide from Diazeniumdiolates. J. Phys. Chem. B 111, 6861-6867 (2007).

 

Yun, B. H., Lee, Y. A., Kim, S. K., Kuzmin, V., Kolbanovskiy, A., Dedon, P. C., Geacintov, N. E., Shafirovich, V. Photosensitized Oxidative DNA Damage: from Hole Injection to Chemical Product Formation and Strand cleavage. J. Am. Chem. Soc. 129, 9321-9332 (2007).

 

Lewis, F. D., Zhu, H., Daublain, P., Fiebig, T., Raytchev, M., Wang, Q., Shafirovich, V. Crossover from Superexchange to Hopping as the Mechanism for Photoinduced Charge Transfer in DNA Hairpin Conjugates. J. Am. Chem. Soc. 128, 791-800 (2006).

 

Crean, C., Geacintov, N. E., Shafirovich, V. Oxidation of Guanine and 8-Oxo-7,8-Dihydroguanine by Carbonate Radical Anions: Insight from Oxygen-18 Labeling Experiments. Angew. Chem., Int. Ed. Engl., 44, 5057-5060 (2005).

 

Misiaszek, R., Crean, C., Geacintov, N. E., Shafirovich, V. Combination of Nitrogen Dioxide Radicals with 8-Oxo-7,8-dihydroguanine and Guanine Radicals in DNA: Oxidation and Nitration End-Products. J. Am. Chem. Soc. 127, 2191-2200 (2005).

 

Misiaszek, R., Uvaydov, Y., Crean, C., Geacintov, N. E., Shafirovich, V. Combination Reactions of Superoxide with 8-Oxo-7,8-Dihydroguanine Radicals in DNA: Kinetics and End-Products. J. Biol. Chem. 280, 6293-6300 (2005).

 

Misiaszek, R., Crean, C., Joffe, A., Geacintov, N. E., Shafirovich, V. Oxidative DNA Damage Associated with Combination of Guanine and Superoxide Radicals and Repair Mechanisms via Radical Trapping. J. Biol. Chem. 279, 32106-32115 (2004).

 

Shafirovich, V., Lymar, S. V. Spin-Forbidden Deprotonation of Aqueous Nitroxyl (HNO). J. Am. Chem. Soc. 125, 6547-6552 (2003).