biostudies-literatureVentura GMinistero dell?Istruzione, dell?Universit? e della Ricerca12914-12922https://www.ebi.ac.uk/biostudies/studies/S-EPMC6644602biostudies-literatureUnknown3(10)Pt(II)-based derivatives bearing a cyanocobalamin (CNCbl) unit were synthesized in aqueous solutions, and the reaction mixtures were examined by reversed-phase liquid chromatography with electrospray ionization and linear ion trap mass spectrometry (MS). Isotopic pattern analysis, multistage mass-spectra (MS/MS and MS3) interpretation, and differential isotopic labeling were used to establish the chemical composition and to suggest the chemical structures of reaction products. When cisplatin (cis-[PtCl2(NH3)2]) was used as a Pt(II) drug derivative, a coordination bond between diamminemonochloroplatinum(II) and the cyano group of CNCbl, in turn linked covalently to the vitamin Co(III) ion, occurred. The resulting conjugate with a CoIII-CN-PtII bridge was MS detected as a doubly positive charged ion with the prevailing isotopologue at m/z 810.26 (empirical formula [C63H95ClCoIIIN16O14PPt]2+). Likewise, a peak signal centered at m/z 811.26 was observed when 15N-labeled cisplatin cis-[PtCl2(15NH3)2] was used as Pt(II) complex, thus confirming the presence of both the cisplatin amino groups in the conjugate. A bifunctional conjugate was obtained between CNCbl and the cis-diamminediaquaplatinum(II), that is, cis-[Pt(NH3)2(H2O)2]2+; in this case, the planar coordination complex of Pt(II) was also involved in a covalent bond with the oxygen atom of one of the CNCbl amide moieties. The peak signal detected at m/z 792.26 (empirical formula [C63H94CoIIIN16O14PPt]2+) changed to m/z 793.26 when the labeled cis-[Pt(15NH3)2(H2O)2]2+ complex was adopted for conjugation. Comparison between MS/MS spectra allowed an extended structural characterization of both conjugates, as such or 15N-labeled. Two-dimensional heteronuclear (1H-15N) single quantum correlation NMR spectroscopy, applied to 15N-labeled conjugates, supported the hypotheses made on the Pt(II) coordination in both cases.ACS omegaStructural Elucidation of Cisplatin and Hydrated cis-Diammineplatinum(II) Complex Conjugated with Cyanocobalamin by Liquid Chromatography with Electrospray Ionization-Mass Spectrometry and Multistage Mass Spectrometry.PMC6644602PONa3_00395/1 ?BIOSCIENZE & SALUTE (B&H)?Arnesano FCataldi TRILosito IPanella ANardella MICalvano CDPalmisano FVentura GfalseStructural Elucidation of Cisplatin and Hydrated cis-Diammineplatinum(II) Complex Conjugated with Cyanocobalamin by Liquid Chromatography with Electrospray Ionization-Mass Spectrometry and Multistage Mass Spectrometry.Pt(II)-based derivatives bearing a cyanocobalamin (CNCbl) unit were synthesized in aqueous solutions, and the reaction mixtures were examined by reversed-phase liquid chromatography with electrospray ionization and linear ion trap mass spectrometry (MS). Isotopic pattern analysis, multistage mass-spectra (MS/MS and MS3) interpretation, and differential isotopic labeling were used to establish the chemical composition and to suggest the chemical structures of reaction products. When cisplatin (cis-[PtCl2(NH3)2]) was used as a Pt(II) drug derivative, a coordination bond between diamminemonochloroplatinum(II) and the cyano group of CNCbl, in turn linked covalently to the vitamin Co(III) ion, occurred. The resulting conjugate with a CoIII-CN-PtII bridge was MS detected as a doubly positive charged ion with the prevailing isotopologue at m/z 810.26 (empirical formula [C63H95ClCoIIIN16O14PPt]2+). Likewise, a peak signal centered at m/z 811.26 was observed when 15N-labeled cisplatin cis-[PtCl2(15NH3)2] was used as Pt(II) complex, thus confirming the presence of both the cisplatin amino groups in the conjugate. A bifunctional conjugate was obtained between CNCbl and the cis-diamminediaquaplatinum(II), that is, cis-[Pt(NH3)2(H2O)2]2+; in this case, the planar coordination complex of Pt(II) was also involved in a covalent bond with the oxygen atom of one of the CNCbl amide moieties. The peak signal detected at m/z 792.26 (empirical formula [C63H94CoIIIN16O14PPt]2+) changed to m/z 793.26 when the labeled cis-[Pt(15NH3)2(H2O)2]2+ complex was adopted for conjugation. Comparison between MS/MS spectra allowed an extended structural characterization of both conjugates, as such or 15N-labeled. Two-dimensional heteronuclear (1H-15N) single quantum correlation NMR spectroscopy, applied to 15N-labeled conjugates, supported the hypotheses made on the Pt(II) coordination in both cases.2018-01-01T00:00:00Z2018 Oct2024-02-14T20:16:57.39Z2019-08-31T07:03:57ZS-EPMC66446023145801410.1021/acsomega.8b01879