title: Metallocene-DNA: synthesis, molecular and electronic structure and DNA incorporation of C5-ferrocenylthymidine derivatives.
abstract: Ferrocenylthymidine derivatives have been prepared by Pd-catalysed cross-coupling between ethynylferrocene or vinylferrocene and 5-iodo-2'-deoxyuridine. In the latter case a mixture of trans (2a) and gem (2b) isomers was obtained. The cis-vinylferrocenyl (2c), and ethylferrocenyl (3) derivatives were obtained by catalytic hydrogenation of ethynylferrocenyl-dT (1a), and 2c respectively. Single-crystal X-ray data for 1a, the ferrocenyl-2'furano-pyrimidone 1b, and 2a show that the nucleobase is essentially co-planar with the substituted Cp ring of the metallocene. The selective reduction of the linkage between the ferrocenyl and thymidine moieties, from -C identical to C- to -CH2CH2-, causes a shift in the reduction potential of -124 mV. DFT calculations for the one-electron oxidised species indicate that the diminished conjugation reduces the spin transfer onto the bridging C2 group, but has less effect on the extent transferred to the nucleobase from the ferrocenyl group. Compound 1a was incorporated site-specifically into DNA oligonucleotides by using automated solid-phase methods. However, some interconversion of 1a-->1b occurs, even under rapid mild conditions of deprotection.
authors.affiliation: Department of Chemistry, University of Newcastle upon Tyne, Newcastle upon Tyne, NE1 7RU, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Pike
authors.forename: Lyndsey C
authors.initials: LC
authors.lastname: Ryder
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Horrocks
authors.forename: William
authors.initials: W
authors.lastname: Clegg
authors.forename: Mark R J
authors.initials: MR
authors.lastname: Elsegood
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Connolly
authors.forename: Andrew
authors.initials: A
authors.lastname: Houlton
mesh_terms: D020029:Base Pairing; D001665:Binding Sites; D004247:DNA / Q000138:chemical synthesis* / Q000737:chemistry; D004583:Electrons; D005296:Ferrous Compounds / Q000737:chemistry; D007065:Idoxuridine / Q000737:chemistry; D000075163:Metallocenes; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D013936:Thymidine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D005296:Ferrous Compounds; D000075163:Metallocenes; D009838:Oligodeoxyribonucleotides; D009942:Organometallic Compounds; C013108:metallocene; D004247:DNA; D007065:Idoxuridine; C004998:ferrocene; D013936:Thymidine