title: Ab initio studies of the reaction of hydrogen transfer from DNA to the calicheamicinone diradical.
abstract: BACKGROUND
  The biological activity of enediyne chemotherapeutic (anti-cancer) agents is attributed to their ability to cleave duplex DNA. Part of the reaction of cleavage is the abstraction of hydrogens from the deoxyribose moiety of DNA by the biradical formed via a Bergman rearrangement.
  
  
  METHODS
  The mechanism of the reaction of abstraction of two hydrogen atoms from two deoxyribophosphate molecules by the calicheamicinone biradical is studied with ab initio calculations at Hartree-Fock and post-Hartree-Fock level. The Titan program is used to perform the calculations.
  
  
  RESULTS
  It is found that the reactions are exothermic and thus thermodynamically reasonable.
  
  
  CONCLUSIONS
  The mechanism of DNA cleavage by the enediyne-containing drugs is likely to proceed by the abstraction of the hydrogens from deoxyribose by the biradical formed by the drug. Further studies should determine in which way the modification of the drug's structure would make this reaction even more exothermic and, thus, more likely to occur.
authors.affiliation: City University of New York, John Jay College and Graduate Center, New York, NY 10019, USA. acransg6@AOL.com
authors.forename: A M
authors.initials: AM
authors.lastname: Sapse
authors.forename: R
authors.initials: R
authors.lastname: Rothchild
authors.forename: R
authors.initials: R
authors.lastname: Kumar
authors.forename: J W
authors.initials: JW
authors.lastname: Lown
mesh_terms: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D005609:Free Radicals; D006859:Hydrogen / Q000737:chemistry*; D008956:Models, Chemical; D013816:Thermodynamics
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005609:Free Radicals; C422086:calicheamicinone; D006859:Hydrogen; D004247:DNA