title: Photochemical generation and reactivity of the 5,6-dihydrouridin-6-yl radical.
abstract: Nucleobase radicals are the major family of reactive intermediates formed when nucleic acids are exposed to hydroxyl radical, which is produced by gamma-radiolysis and Fe.EDTA. Significant advances have been made in understanding the role of nucleobase radicals in oxidative DNA damage by independently generating these species from photochemical precursors. However, this approach has been used much less frequently to study RNA molecules. Norrish type I photocleavage of the tert-butyl ketone (2b) enabled studying the reactivity of 5'-benzoyl-5,6-dihydrouridin-6-yl (1b). High mass balances were observed under aerobic or anaerobic conditions, and O(2) did not affect the photochemical conversion of the ketone (2b) to 1b. Competition studies with O(2) indicate that the radical abstracts hydrogen atoms from beta-mercaptoethanol with a bimolecular rate constant = 2.6 +/- 0.5 x 10(6) M(-1)s(-1). The major product formed in the presence of O(2) was 5'-benzoyl-6-hydroxy-5,6-dihydrouridine (6). In contrast, 5-benzoyl-ribonolactone (7), a hypothetical product resulting from C1'-hydrogen atom abstraction by the peroxyl radical, could not be detected. Overall, tert-butyl ketone 2b is a clean source of 5'-benzoyl-5,6-dihydrouridin-6-yl (1b) and should prove useful for studying the reactivity of the respective radical in RNA.
authors.affiliation: Department of Chemistry, Johns Hopkins University, 3400 N. Charles St., Baltimore, Maryland 21218, USA.
authors.forename: Cory A
authors.initials: CA
authors.lastname: Newman
authors.forename: Marino J E
authors.initials: MJ
authors.lastname: Resendiz
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Sczepanski
authors.forename: Marc M
authors.initials: MM
authors.lastname: Greenberg
mesh_terms: D001565:Benzoates / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000528:radiation effects; D004249:DNA Damage; D005609:Free Radicals / Q000737:chemistry / Q000528:radiation effects; D007700:Kinetics; D007783:Lactones / Q000737:chemistry; D008623:Mercaptoethanol / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D010777:Photochemistry; D010782:Photolysis; D012266:Ribose / Q000031:analogs & derivatives / Q000737:chemistry; D013237:Stereoisomerism; D014529:Uridine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000528:radiation effects
chemical_list: D001565:Benzoates; D005609:Free Radicals; D007783:Lactones; C012360:6-hydroxy-5,6-dihydrouridine; C057020:ribonolactone; D008623:Mercaptoethanol; D012266:Ribose; D004247:DNA; D010100:Oxygen; D014529:Uridine
references.citation: Org Lett. 2000 Apr 20;2(8):1085-8
references.pmid: 10804560
references.citation: J Am Chem Soc. 2006 Jan 18;128(2):485-91
references.pmid: 16402835
references.citation: Int J Radiat Biol. 1990 Jun;57(6):1123-39
references.pmid: 1971839
references.citation: J Am Chem Soc. 1975 Apr 16;97(8):2277-8
references.pmid: 1133412
references.citation: Chem Pharm Bull (Tokyo). 1983 Jun;31(6):2164-7
references.pmid: 6640797
references.citation: Annu Rev Biochem. 2002;71:51-70
references.pmid: 12045090
references.citation: Chemistry. 2004 Mar 5;10(5):1249-55
references.pmid: 15007814
references.citation: J Am Chem Soc. 2003 Nov 5;125(44):13376-8
references.pmid: 14583031
references.citation: J Am Chem Soc. 2005 Mar 23;127(11):3692-3
references.pmid: 15771492
references.citation: Org Biomol Chem. 2007 Jan 7;5(1):18-30
references.pmid: 17164902
references.citation: Curr Opin Struct Biol. 2002 Oct;12(5):648-53
references.pmid: 12464318
references.citation: J Phys Chem B. 2006 Jul 13;110(27):13582-9
references.pmid: 16821885
references.citation: Eur J Clin Invest. 2004 May;34(5):323-7
references.pmid: 15147328
references.citation: J Am Chem Soc. 2007 Apr 4;129(13):4089-98
references.pmid: 17335214
references.citation: Free Radic Biol Med. 2008 Apr 15;44(8):1493-505
references.pmid: 18258207
references.citation: Bioorg Med Chem. 2001 Sep;9(9):2341-6
references.pmid: 11553474
references.citation: Curr Opin Chem Biol. 2005 Apr;9(2):127-34
references.pmid: 15811796
references.citation: J Am Chem Soc. 2001 Jun 6;123(22):5181-7
references.pmid: 11457379
references.citation: Nucleic Acids Res. 2006 May 08;34(8):e64
references.pmid: 16682443
references.citation: J Org Chem. 2004 Oct 15;69(21):6974-8
references.pmid: 15471441
references.citation: J Org Chem. 2003 May 30;68(11):4275-80
references.pmid: 12762726
references.citation: Chem Res Toxicol. 2005 Dec;18(12):1897-906
references.pmid: 16359180
references.citation: J Am Chem Soc. 2002 Aug 7;124(31):9062-3
references.pmid: 12149005
references.citation: Int J Radiat Biol. 1991 May;59(5):1127-45
references.pmid: 1675234
references.citation: Methods Enzymol. 2000;317:353-68
references.pmid: 10829290
references.citation: J Am Chem Soc. 2008 Oct 1;130(39):12890-1
references.pmid: 18778053
references.citation: Nature. 2008 Oct 30;455(7217):1268-72
references.pmid: 18784650
references.citation: Acc Chem Res. 2000 Sep;33(9):631-6
references.pmid: 10995201
references.citation: Science. 1998 Mar 20;279(5358):1940-3
references.pmid: 9506944
references.citation: Biomark Med. 2007 Aug;1(2):293-312
references.pmid: 20477404
references.citation: J Am Chem Soc. 2008 Jan 30;130(4):1296-303
references.pmid: 18179212