Complexation of halide ions to tyrosine: role of non-covalent interactions evidenced by IRMPD spectroscopy

The binding motifs in the halide adducts with tyrosine ([Tyr + X]-, X = Cl, Br, I) have been investigated and compared with the analogues with 3-nitrotyrosine (nitroTyr), a biomarker of protein nitration, in a solvent-free environment by mass-selected infrared multiple photon dissociation (IRMPD) spectroscopy over two IR frequency ranges, namely 950–1950 and 2800–3700 cm-1. Extensive quantum chemical calculations at B3LYP, B3LYP-D3 and MP2 levels of theory have been performed using the 6-311++G(d,p) basis set to determine the geometry, relative energy and vibrational properties of likely isomers and interpret the measured spectra. A diagnostic carbonyl stretching band at B1720 cm-1 from the intact carboxylic group characterizes the IRMPD spectra of both [Tyr + X]- and [nitroTyr + X]-, revealing that the canonical isomers (maintaining intact amino and carboxylic functions) are the prevalent structures. The spectroscopic evidence reveals the presence of multiple non-covalent forms. The halide complexes of tyrosine conform to a mixture of plane and phenol isomers. The contribution of phenol-bound isomers is sensitive to anion size, increasing from chloride to iodide, consistent with the decreasing basicity of the halide, with relative amounts depending on the relative energies of the respective structures. The stability of the most favorable phenol isomer with respect to the reference plane geometry is in fact 1.3, -2.1, -6.8 kJ mol-1, for X = Cl, Br, I, respectively. The change in p-acidity by ring nitration also stabilizes anion–p interactions yielding ring isomers for [nitroTyr + X]-, where the anion is placed above the face of the aromatic ring

Interaction of Cisplatin with Adenine and Guanine: A Combined IRMPD, MS/MS, and Theoretical Study

International audienceInfrared multiple photon dissociation (IRMPD) spectroscopy of cis-[Pt(NH3)2(G)Cl]+ and cis-[Pt(NH3)2(A)Cl]+ ions (where A is adenine and G is guanine) has been performed in two spectral regions, 950-1900 and 2900-3700 cm-1. Quantum chemical calculations at the B3LYP/LACV3P/6-311G** level yield the optimized geometries and IR spectra for the conceivable isomers of cis-[Pt(NH3)2(G)Cl]+ and cis-[Pt(NH3)2(A)Cl]+, whereby the cisplatin residue is attached to the N7, N3, or carbonyl oxygen atom, (O6), of guanine and to the N7, N3, or N1 position of adenine, respectively. In addition to the conventional binding sites of native adenine, complexes with N7-H tautomers have also been considered. In agreement with computational results, the IR characterization of cis-[Pt(NH3)2(G)Cl]+ points to a covalent structure where Pt is bound to the N7 atom of guanine. The characterized conformer has a hydrogen-bonding interaction between a hydrogen atom of one NH3 ligand and the carbonyl group of guanine. The experimental C═O stretching feature of cis-[Pt(NH3)2(G)Cl]+ at 1718 cm-1, remarkably red-shifted with respect to an unperturbed C═O stretching mode, is indicative of a lengthened CO bond in guanine, a signature that this group is involved in hydrogen bonding. The IRMPD spectra of cis-[Pt(NH3)2(A)Cl]+ are consistent with the presence of two major isomers, PtAN3 and PtAN1, where Pt is bound to the N3 and N1 positions of native adenine, respectively

Vibrational Spectroscopy of Platinum(II) Complexes Relevant in Antitumor Activity

International audienceCisplatin (cis-diamminedichloroplatinum(II) is the first platinum-based antitumor agent, and it is still widely used in chemotherapy. In the cytoplasm, the administered drug undergoes spontaneous hydrolysis by nucleophilic substitution of chloride with water. The cationic chloro-monoaqua form, cis-[PtCl(NH3)2(H2O)]+, characterized by a pKa value of 6.5, is the relevant intermediate at physiological pH, that can ultimately give rise to DNA and protein adducts through easy substitution of water by nitrogen/sulfur donor ligands. Electrospray ionization has allowed cis- and trans-[PtCl(NH3)2(H2O)]+ species to be obtained as free ions in the gas phase where they were sampled by infrared multiple photon dissociation (IRMPD) spectroscopy in the NH/OH stretching frequency range (3200−3800 cm−1), using a tabletop optical parametric oscillator/amplifier (OPO/OPA) laser system coupled to a quadrupole ion trap mass spectromete

Reconstructing the infrared spectrum of a peptide from representative conformers of the full canonical ensemble

Leucine enkephalin (LeuEnk), a biologically active endogenous opioid pentapeptide, has been under intense investigation because it is small enough to allow efficient use of sophisticated computational methods and large enough to provide insights into low-lying minima of its conformational space. Here, we reproduce and interpret experimental infrared (IR) spectra of this model peptide in gas phase using a combination of replica-exchange molecular dynamics simulations, machine learning, and ab initio calculations. In particular, we evaluate the possibility of averaging representative structural contributions to obtain an accurate computed spectrum that accounts for the corresponding canonical ensemble of the real experimental situation. Representative conformers are identified by partitioning the conformational phase space into subensembles of similar conformers. The IR contribution of each representative conformer is calculated from ab initio and weighted according to the population of each cluster. Convergence of the averaged IR signal is rationalized by merging contributions in a hierarchical clustering and the comparison to IR multiple photon dissociation experiments. The improvements achieved by decomposing clusters containing similar conformations into even smaller subensembles is strong evidence that a thorough assessment of the conformational landscape and the associated hydrogen bonding is a prerequisite for deciphering important fingerprints in experimental spectroscopic data.</p

Probing the competition among different coordination motifs in metal-ciprofloxacin complexes through IRMPD spectroscopy and DFT calculations

The vibrational spectra of ciprofloxacin complexes with monovalent (Li+, Na+, K+, Ag+) and polyvalent (Mg2+, Al3+) metal ions are recorded in the range 1000-1900 cm(-1) by means of infrared multiple-photon dissociation (IRMPD) spectroscopy. The IRMPD spectra are analyzed and interpreted in the light of density functional theory (DFT)-based quantum chemical calculations in order to identify the possible structures present under our experimental conditions. For each metal-ciprofloxacin complex, four isomers are predicted, considering different chelation patterns. A good agreement is found between the measured IRMPD spectrum and the calculated absorption spectrum of the most stable isomer for each complex. Metal ion size and charge are found to drive the competition among the different coordination motifs: small size and high charge density metal ions prefer to coordinate the quinolone between the two carbonyl oxygen atoms, whereas large-size metal ions prefer the carboxylate group as a coordination site. In the latter case, an intramolecular hydrogen bond compensates the weaker interaction established by these cations. The role of the metal cation on the stabilization of ionic and nonionic structures of ciprofloxacin is also investigated. It is found that large-size metal ions preferentially stabilize charge separated motifs and that the increase of metal ion charge has a stabilizing effect on the zwitterionic form of ciprofloxacin

T-REX OU4 HIRES: the high resolution spectrograph for the E-ELT

The goal of this unit was to consolidate the project for the construction of the high resolution spectrometer of the E-ELT (HIRES). The task included the development of scientific cases and tools to predict the instrumental performances. From the technical point of view it included several R&D activities in collaboration with highly specialized Italian companies; it culminated with the detailed design of a highly modular instrument based on well established technologies. From the management point of view it lead to the consolidation of a large international consortium that spans over 12 countries and includes most of the European and ESO-related institutes interested in high resolution spectroscopy. This consortium is led by INAF; its formal creation is awaiting the official call by ESO for the phase-A study for the HIRES instrument of the E-ELT

Structure of protonated thymidine characterized by InfraRed Multiple Photon Dissociation and quantum calculations

International audienceRationaleMany fundamental studies are motivated by the probable relationship between the presence of rare enol tautomers of nucleobases and point mutation developing during nucleic acid replication. The evaluation of the tautomeric behaviour of nucleobases is therefore of fundamental importance. This can be probed in the gas phase by combining action spectroscopy and mass spectrometry.MethodsExperimental Infrared Multiple Photon Dissociation spectra in the fingerprint region of electrospray-generated and subsequently selected ions were recorded at the CLIO free electron laser (FEL) facility, by coupling the FEL to a quadrupole ion trap, and compared to calculated harmonic vibrational infrared spectra of the different low-lying isomers computed at the B3LYP/6-31++G(d,p) level. Relative energies were refined using the extended basis set 6-311++G(3df,2p).ResultsThe Density Functional Theory (DFT) study shows that, as for protonated thymine, the global energy minimum of protonated thymidine corresponds to an enol tautomer, whose infrared absorption spectrum is found to be in very good agreement with the experimental IRMPD spectrum. A very weak IRMPD signal observed at ~1780 cm–1 is very likely the signature of an oxo tautomer. Consequently, as for thymine, protonated thymidine generated by electrospray corresponds to a mixture of at least two tautomeric forms.ConclusionsTautomerization can be characterized by IRMPD spectroscopy. Interestingly, the dominant enolic tautomeric form(s) presently observed cannot be directly generated from the most stable neutral tautomer of the thymine residue