TY - JOUR
T1 - Diverse and unexpected outcomes from oxidation of the platinum(II) anticancer agent [Pt{(p-BrC6F4)NCH2CH2NEt2}Cl(py)] by hydrogen peroxide
AU - Ojha, Ruchika
AU - Mason, Dayna
AU - Forsyth, Craig M.
AU - Deacon, Glen B.
AU - Junk, Peter C.
AU - Bond, Alan M.
PY - 2021/5
Y1 - 2021/5
N2 - Oxidation of the anti-tumour agent [Pt{(p-BrC6F4)NCH2CH2NEt2}Cl(py)], 1 (py = pyridine) with hydrogen peroxide under a variety of conditions yields a range of organoenamineamidoplatinum(II) compounds [Pt{(p-BrC6F4)NCH=C(X)NEt2}Cl(py)] (X = H, Cl, Br) as well as species with shared occupancy involving H, Cl and Br. Thus, oxidation of the –CH2–CH2– backbone (dehydrogenation) occurs, often accompanied by substitution. Oxidation of 1 with H2O2 in acetone yielded 1:1 co-crystallized [Pt{(p-BrC6F4)NCH=CHNEt2}Cl(py)], 1H and [Pt{(p-BrC6F4)NCH=C(Cl)NEt2}Cl(py)], 1Cl. The former was obtained pure in low yield from the oxidation of 1 with (NH4)2[Ce(NO3)6] in acetone, and the latter was obtained from 1 and H2O2 in CH2Cl2 at near reflux. From the latter reaction under vigorous refluxing [Pt{(p-BrC6F4)NCH=C(Br)NEt2}Cl(py)], 1Br was isolated. In refluxing acetonitrile, oxidation of 1 with H2O2 yielded [Pt{(p-BrC6F4)NCH=C(H0.25Br0.75)NEt2}Cl(py)], 1H0.25Br0.75, in which the alkene is mainly substituted by Br in a dual occupancy. Treatment of 1 with H2O2 and tetrabutylammonium hydroxide in acetone at room temperature formed [Pt{(p-HC6F4)NCH2CH2NEt2}Cl(py)], 2. Oxidation of [Pt{(p-HC6F4)NCH2CH2NEt2}Br(py)], 3 with H2O2 in boiling acetonitrile gave the ligand oxidation product [Pt{(p-HC6F4)NCH=C(Br)NEt2}Br(py)], 3Br. All major products were identified by X-ray crystallography as well as by 1H and 19F NMR spectra. In cases of mixed crystals or dual occupancy compounds, the 19F and 1H NMR spectra showed dissociation into the components in the solution in the same proportions as in isolated crystalline material.
AB - Oxidation of the anti-tumour agent [Pt{(p-BrC6F4)NCH2CH2NEt2}Cl(py)], 1 (py = pyridine) with hydrogen peroxide under a variety of conditions yields a range of organoenamineamidoplatinum(II) compounds [Pt{(p-BrC6F4)NCH=C(X)NEt2}Cl(py)] (X = H, Cl, Br) as well as species with shared occupancy involving H, Cl and Br. Thus, oxidation of the –CH2–CH2– backbone (dehydrogenation) occurs, often accompanied by substitution. Oxidation of 1 with H2O2 in acetone yielded 1:1 co-crystallized [Pt{(p-BrC6F4)NCH=CHNEt2}Cl(py)], 1H and [Pt{(p-BrC6F4)NCH=C(Cl)NEt2}Cl(py)], 1Cl. The former was obtained pure in low yield from the oxidation of 1 with (NH4)2[Ce(NO3)6] in acetone, and the latter was obtained from 1 and H2O2 in CH2Cl2 at near reflux. From the latter reaction under vigorous refluxing [Pt{(p-BrC6F4)NCH=C(Br)NEt2}Cl(py)], 1Br was isolated. In refluxing acetonitrile, oxidation of 1 with H2O2 yielded [Pt{(p-BrC6F4)NCH=C(H0.25Br0.75)NEt2}Cl(py)], 1H0.25Br0.75, in which the alkene is mainly substituted by Br in a dual occupancy. Treatment of 1 with H2O2 and tetrabutylammonium hydroxide in acetone at room temperature formed [Pt{(p-HC6F4)NCH2CH2NEt2}Cl(py)], 2. Oxidation of [Pt{(p-HC6F4)NCH2CH2NEt2}Br(py)], 3 with H2O2 in boiling acetonitrile gave the ligand oxidation product [Pt{(p-HC6F4)NCH=C(Br)NEt2}Br(py)], 3Br. All major products were identified by X-ray crystallography as well as by 1H and 19F NMR spectra. In cases of mixed crystals or dual occupancy compounds, the 19F and 1H NMR spectra showed dissociation into the components in the solution in the same proportions as in isolated crystalline material.
KW - Br liberation
KW - Hydrogen peroxide
KW - Olefinic substitution
KW - Oxidation
KW - Oxidation of the ligand
KW - Platinum anti-tumour agents
UR - http://www.scopus.com/inward/record.url?scp=85102609045&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2021.111360
DO - 10.1016/j.jinorgbio.2021.111360
M3 - Article
AN - SCOPUS:85102609045
SN - 0162-0134
VL - 218
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
M1 - 111360
ER -