title: Dirhodium(II,II) complexes: molecular characteristics that affect in vitro activity.
abstract: In the series Rh2(O2CR)4 (R=CH3, 1; R=CF3, 2), [Rh2(O2CR)2(phen)2]2+ (R=CH3, 3; R=CF3, 4), and [Rh2(O2CR)2(dppz)2]2+ (R=CH3, 5; R=CF3, 6), 2, 4, and 6 are twice as cytotoxic as 1, 3, and 5, respectively. The substitution reactions of 2 with 9-ethylguanine at various temperatures take place at faster rates than those of 1, and the activation energy Ea(1)=69+/-4 kJ/mol is twice Ea(2)=35+/-2 kJ/mol. The higher cytotoxicities of [Rh2(micro-O2CCH3)2(eta1-O2CCH3)L(MeOH)]+ (L=dppz, 7; L=dppn, 8) relative to [Rh2(micro-O2CCH3)2(bpy)L]2+ (L=dppz, 10; L=dppn, 11) are attributed to the labile equatorial groups in 7 and 8 not present in 10 and 11. The toxicities of complexes 1-8 are not related to their charge or the ease by which they transverse the cellular membrane but to the lability of the ligands on the dirhodium core.
authors.affiliation: Department of Chemistry, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Alfredo M
authors.initials: AM
authors.lastname: Angeles-Boza
authors.forename: Helen T
authors.initials: HT
authors.lastname: Chifotides
authors.forename: J Dafhne
authors.initials: JD
authors.lastname: Aguirre
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Chouai
authors.forename: Patty K-L
authors.initials: PK
authors.lastname: Fu
authors.forename: Kim R
authors.initials: KR
authors.lastname: Dunbar
authors.forename: Claudia
authors.initials: C
authors.lastname: Turro
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D002614:Chelating Agents / Q000737:chemistry; D005347:Fibroblasts / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008024:Ligands; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010618:Phenanthrolines / Q000737:chemistry; D010619:Phenazines / Q000737:chemistry; D012238:Rhodium; D012867:Skin / Q000166:cytology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D008024:Ligands; D009942:Organometallic Compounds; D010618:Phenanthrolines; D010619:Phenazines; D015082:2,2'-Dipyridyl; D012238:Rhodium