Highly selective metal mediated ortho-alkylation of phenol. First platinum containing organometallic chromane analogues.
We were able, for the first time, to synthesize and characterize Pt derivatives with a structural shape similar to vitamin E, having a metalla-chromane core. The formation reaction mechanism includes an unexpected highly selective ortho aromatic electrophilic substitution on phenol, operated by [PtCl(eta(1)-C(2)H(4)OR)(N-N)], R = Me or Ph, and a final cyclization step. The X-ray structure of one of the new metalla-chromane complexes [Pt(EtPh)(phen)],1a, (EtPh = 2-(ethan-2'-yl-kC(1))-1-phenolato-k0(1), phen = 1,10-phenanthroline) is reported. Cytotoxicity and Pt uptake measurements, performed on HeLa cancer cells, show an interesting structure-activity correlation for the new metalla-chromane analogues 1a and [Pt(MeOEtPh)(phen)], 1b, (MeOEtPh = 2-(ethan-2'-yl-kC(1))-4-(methoxy)-1-phenolato-k0(1)), being the structurally closest to vitamin E and also the most active.
Vecchio
Vita M
VM
Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Via Provinciale Lecce-Monteroni, I-73100 Lecce, Italy.
Benedetti
Michele
M
Migoni
Danilo
D
De Pascali
Sandra A
SA
Ciccarese
Antonella
A
Marsigliante
Santo
S
Capitelli
Francesco
F
Fanizzi
Francesco P
FP
D000478:Alkylation; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000737:chemistry*; D002945:Cisplatin / Q000633:toxicity; D018360:Crystallography, X-Ray; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D019800:Phenol / Q000737:chemistry*; D017671:Platinum Compounds / Q000737:chemistry*; D014810:Vitamin E / Q000737:chemistry
D002839:Chromans; D009942:Organometallic Compounds; D017671:Platinum Compounds; D014810:Vitamin E; D019800:Phenol; D002945:Cisplatin