Binding Motifs of Carboplatin and Oxaliplatin with Guanine: A Combined MS/MS, IRMPD, and Theoretical Study.

Complexes generated in the gas phase involving the purine nucleobase guanine bound to second and third generation platinum drugs, namely, carboplatin (CarboPt) and oxaliplatin (OxaliPt), were investigated by combining tandem mass spectrometry, collision-induced dissociation (CID), infrared multiple photon dissociation spectroscopy (IRMPD), and density functional theory (DFT) calculations. As the first step, a spectroscopic characterization of the protonated platinum drugs was accomplished. Protonation of both CarboPt and OxaliPt in the gas phase occurs on one of the two carbonyl groups of the cyclobutanedicarboxylate and oxalate ligand, respectively. Such protonation has been postulated by several theoretical studies as a key preliminary step in the hydrolysis of Pt drugs under acidic conditions. Subsequently, the protonated drugs react with guanine in solution to generate a complex of general formula [Pt drug + H + guanine]+, which was then mass-selected. CID experiments provided evidence of the presence of strong binding between guanine and platinum-based drugs within the complexes. The structures of the two complexes have also been examined by comparing the experimental IRMPD spectra recorded in two spectral regions with DFT-computed IR spectra. For each system, the IRMPD spectra agree with the vibrational spectra calculated for the global minimum structures, which present a monodentate complexation of Pt at the N7 position of canonical guanine. This binding scheme is therefore akin to that observed for cisplatin, while other coordination sites yield substantially less stable species. Interestingly, in the case of oxaliplatin, the IRMPD spectra are consistent with the presence of two isomeric forms very close in energy.

Protonated Forms of Naringenin and Naringenin Chalcone: Proteiform Bioactive Species Elucidated by IRMPD Spectroscopy, IMS, CID-MS, and Computational Approaches.

Naringenin (Nar) and its structural isomer, naringenin chalcone (ChNar), are two natural phytophenols with beneficial health effects belonging to the flavonoids family. A direct discrimination and structural characterization of the protonated forms of Nar and ChNar, delivered into the gas phase by electrospray ionization (ESI), was performed by mass spectrometry-based methods. In this study, we exploit a combination of electrospray ionization coupled to (high-resolution) mass spectrometry (HR-MS), collision-induced dissociation (CID) measurements, IR multiple-photon dissociation (IRMPD) action spectroscopy, density functional theory (DFT) calculations, and ion mobility-mass spectrometry (IMS). While IMS and variable collision-energy CID experiments hardly differentiate the two isomers, IRMPD spectroscopy appears to be an efficient method to distinguish naringenin from its related chalcone. In particular, the spectral range between 1400 and 1700 cm-1 is highly specific in discriminating between the two protonated isomers. Selected vibrational signatures in the IRMPD spectra have allowed us to identify the nature of the metabolite present in methanolic extracts of commercial tomatoes and grapefruits. Furthermore, comparisons between experimental IRMPD and calculated IR spectra have clarified the geometries adopted by the two protonated isomers, allowing a conformational analysis of the probed species.

IRMPD Spectroscopy of Bare Monodeprotonated Genistein, an Antioxidant Flavonoid.

Genistein is a naturally occurring polyphenol belonging to the family of flavonoids with estrogenic properties and proven antioxidant, anti-inflammatory, and hormonal effects. Genistein and its derivatives are involved in radical scavenging activity by way of mechanisms based on sequential proton-loss electron transfer. In view of this role, a detailed structural characterization of its bare deprotonated form, [geni-H]-, generated by electrospray ionization, has been performed by tandem mass spectrometry and infrared multiple photon dissociation (IRMPD) spectroscopy in the 800-1800 cm-1 spectral range. Quantum chemical calculations at the B3LYP/6-311+G(d,p) level of theory were carried out to determine geometries, thermochemical data, and anharmonic vibrational properties of low-lying isomers, enabling to interpret the experimental spectrum. Evidence is gathered that the conjugate base of genistein exists as a single isomeric form, which is deprotonated at the most acidic site (7-OH) and benefits from a strong intramolecular H-bond interaction between 5-OH and the adjacent carbonyl oxygen in the most stable arrangement.