title: Counterions influence reactivity of metal ions with cysteinyldopa model compounds.
abstract: Cysteinyldopas are naturally occurring conjugates of cysteine and dopa (3,4-dihydroxy-l-phenylalanine) that are precursors to red pheomelanin pigments. Metal ions are known to influence pheomelanogenesis in vitro and may be regulatory factors in vivo. Cydo (3-[(2-amino-ethyl)sulfanyl]-4,6-di-tert-butylbenzene-1,2-diol) and CarboxyCydo (2-amino-3-(4,6-di-tert-butyl-2,3-dihydroxyphenylsulfanyl)-propionic acid) are model compounds of cysteinyldopa that retain its metal-binding functionalities but cannot polymerize due to the presence of blocking tert-butyl groups. Cydo reacts readily with zinc(II) acetate or nickel(II) acetate to form a cyclized 1,4-benzothiazine (zine) intermediate that undergoes ring contraction to form benzothiazole (zole) unless it is stabilized by coordination to a metal ion. The crystal structure of [Ni(zine)2] is reported. The acetate counteranion is required for the zinc-promoted reactivity, as neither zinc(II) sulfate nor zinc(II) chloride alone promotes the transformation. The counterion is less important for redox-active copper and iron, which both readily promote the oxidation of Cydo to zine and zole species; Cu(II) complexes of both zine and zole have been characterized by X-ray crystallography. In the case of CarboxyCydo, a 3-carboxy-1,4-benzothiazine intermediate decarboxylates to form [Cu(zine)2] under basic conditions, but in the absence of base forms a mixture of products that includes the carboxylated dimer 2,2'-bibenzothiazine (bi-zine). These products are consistent with species implicated in the pheomelanogenesis biosynthetic pathway and emphasize how metal ions, their counteranions, and reaction conditions can alter pheomelanin product distribution.
authors.affiliation: Department of Chemistry, Duke University, Box 90346, Durham, North Carolina 27708, USA.
authors.forename: Yohannes T
authors.initials: YT
authors.lastname: Tesema
authors.forename: David M
authors.initials: DM
authors.lastname: Pham
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Franz
mesh_terms: D018360:Crystallography, X-Ray; D003548:Cysteinyldopa / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000737:chemistry*; D008958:Models, Molecular; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
chemical_list: D008670:Metals; D003548:Cysteinyldopa