Binding Motifs in the Naked Complexes of Target Amino Acids with an Excerpt of Antitumor Active Biomolecule: An Ion Vibrational Spectroscopy Assay

Abstract

The structures of proton‐bound complexes of 5,7‐dimethoxy‐4H‐chromen‐4‐one (1) and basic amino acids (AAs), namely, histidine (His) and lysine (Lys), have been examined by means of mass spectrometry coupled with IR ion spectroscopy and quantum chemical calculations. This selection of systems is based on the fact that 1 represents a portion of glabrescione B, a natural small molecule of promising antitumor activity, while His and Lys are protein residues lining the cavity of the alleged receptor binding site. These species are thus a model of the bioactive adduct, although clearly the isolated state of the present study bears little resemblance to the complex biological environment. A common feature of [1+AA+H]+ complexes is the presence of a protonated AA bound to neutral 1, in spite of the fact that the gas‐phase basicity of 1 is comparable to those of Lys and His. The carbonyl group of 1 acts as a powerful hydrogen‐bond acceptor. Within [1+AA+H]+ the side‐chain substituents (imidazole group for His and terminal amino group for Lys) present comparable basic properties to those of the α‐amino group, taking part to a cooperative hydrogen‐bond network. Structural assignment, relying on the comparative analysis of the infrared multiple photon dissociation (IRMPD) spectrum and calculated IR spectra for the candidate geometries, derives from an examination over two frequency ranges: 900–1800 and 2900–3700 cm−1. Information gained from the latter one proved especially valuable, for example, pointing to the contribution of species characterized by an unperturbed carboxylic OH or imidazole NH stretching mode.

Molecular Basis for the Remarkably Different Gas-Phase Behavior of Deprotonated Thyroid Hormones Triiodothyronine (T3) and Reverse Triiodothyronine (rT3): A Clue for Their Discrimination?

“…In fact, the only signal characteristic of either one of the two structures is the carboxylic OH bend, which is calculated at 1394 and 1095 cm –1 for rT3_2 and rT3_3 , respectively. Given that, the low activity of [rT3-H] − in the 1400 cm –1 region could, at a first sight, suggest the predominance of rT3_3 , although several examples in the literature point to a poor IRMPD activity of the carboxylic OH bend when strongly interacting with a H-bond acceptor group, such as the amino nitrogen. ,− Thus, the small shoulder at 1370 cm –1 can be likely attributed to rT3_2 . Finally, the experimental band at 1107 cm –1 , which agrees with both the OH bend calculated at 1095 cm –1 for rT3_3 and ring B breathing mode expected at 1097 cm –1 for rT3_2 , does not concur to an unambiguous assignment among the two candidates.…”

Ligation Motifs in Zinc-Bound Sulfonamide Drugs Assayed by IR Ion Spectroscopy

“…However, vibrational modes involving SX bonds were left unchanged, in agreement with evidence reported in previous works [ 60 , 61 , 62 , 63 , 64 ]. Calculated linear IR spectra were convoluted with a Lorentzian profile of 12 cm −1 (fwhm) to facilitate convenient comparison with the experimental IRMPD absorptions [ 65 , 66 ].…”

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

“…IRMPD is an “action” spectroscopy technique that allows one to obtain IR spectra of ionic species mass-isolated in the storage cell of a mass spectrometer. − Comparison of experimental spectra with those obtained by DFT calculations of plausible structures can be used to discriminate isomers and investigate molecular properties, conformational analysis, and binding interactions. This strategy has been applied to a large diversity of biomolecular ions and metal adducts, such as nucleotides, − modified amino acids and peptides, − metabolites, − polyphenols, − and chalcones …”

“…This strategy has been applied to a large diversity of biomolecular ions and metal adducts, such as nucleotides, 29−31 modified amino acids and peptides, 32−34 metabolites, 35−37 polyphenols, 38−42 and chalcones. 43 The main purpose of this contribution is to determine structural features and conformational distribution of protonated Nar and ChNar isolated in the gas phase by exploiting a combined approach based on electrospray ionization (ESI) coupled to (high-resolution) mass spectrometry, IRMPD action spectroscopy, theoretical DFT calculations, and ion mobility-mass spectrometry (IMS). This study was carried out on protonated species to avoid possible naringenin/naringenin chalcone isomerization during the ionization processes in the ESI source or solution.…”