Search

Distinguishing positional isomers, such as compounds having different substitution patterns on an aromatic ring, presents a significant challenge for mass spectrometric analyses and is a frequently encountered difficulty in, for example, drug metabolism research. Here, we demonstrate infrared ion spectroscopy (IRIS) as a promising new mass spectrometry-based technique that easily differentiates between positional isomers of disubstituted phenyl-containing compounds. By analyzing different substitution patterns over several sets of isomeric compounds, we show that IRIS produces a highly consistent and distinct pattern of IR bands, especially in the range between 650 and 900 cm-1, that are mostly independent of the specific chemical functionality contained in the substituent group. These patterns are accurately predicted by quantum-chemically computed IR spectra and correspond well with tabulated IR group-frequencies known from conventional absorption spectroscopy. Therefore, we foresee that this method will be generally applicable to disubstituted phenyl-containing compounds and that direct interpretation of experimental IRIS spectra in terms of ortho-, meta- or para-substitution is possible, even without comparison to experimental or computationally predicted reference spectra. Strategies for the analysis of larger compounds having more congested IR spectra as well as of compounds having low (electrospray) ionization efficiencies are presented in order to demonstrate the broad applicability of this methodology.

Microspheres containing radioactive 166holmium-acetylacetonate are employed in emerging radionuclide therapies for the treatment of malignancies. At the molecular level, details on the coordination geometries of the Ho complexes are however elusive. Infrared ion spectroscopy (IRIS) was used to characterize several 165Ho-acetylacetonate complexes derived from non-radioactive microspheres. The coordination geometry of four distinct ionic complexes were fully assigned by comparison of their measured IR spectra with spectra calculated at the density functional theory (DFT) level. The coordination of each acetylacetonate ligand is dependent on the presence of other ligands, revealing an asymmetric chelation motif in some of the complexes. A fifth, previously unknown constituent of the microspheres was identified as a coordination complex containing an acetic acid ligand. These results pave the way for IRIS-based identification of microsphere constituents upon neutron activation of the metal center.

The distinct basicity of the guanidinium side-group of arginine (Arg) sustains specific interactions involved in essential biochemical processes. The sensing of arginine is therefore key in modern biotechnology and bioanalysis. In this context, the development of molecular receptors based on crown ether building blocks has demonstrated great potential. We investigate the complexes formed by arginine with two benchmark macrocycles, 12-crown-4 (1,4,7,10-tetraoxacyclododecane) and its N-substituted analog cyclen (1,4,7,10-tetraazacyclododecane). Isolated complexes with a net charge +1 are characterized with infrared action vibrational spectroscopy and quantum mechanical computations in order to determine the most stable coordination arrangements and to elucidate the location of the protons involved. Remarkably, although arginine retains a net positive charge in its complex with 12-crown-4, it becomes zwitterionic in the cyclen complex. In this latter case, the guanidinium group remains protonated while a proton transfer from the carboxylic group occurs, leading to a charged −NH2+ moiety in cyclen. Natural bond orbital analysis is employed to characterize the intermolecular H-bonds responsible for the stability of both complexes. Protonated arginine interacts with 12-crown-4 through the guanidinium side group, in a conformation that resembles the one expected for crown–Arg binding in peptidic chains. In contrast, the cyclen complex involves the coordination of the carboxylate anionic group with a N–H bond of the protonated amine group cyclen, and plausible but less relevant interactions with the guanidinium group.

The antibiotic activity of nonactin is sustained by its ability to transport K+ across lipophilic phases, e.g., the cell membranes. Such a feature can be traced back to a specific ionophoric behavior and to a balanced hydrophobicity modulated by the formation of a cation complex. In this study, the dominant conformations and coordination arrangements in the alkali cation complexes (Na+, K+, Cs+) of nonactin are characterized by means of action vibrational spectroscopy and quantum chemical computations. The low energy conformers of the complexes comprise compact inclusion structures, in which the cation interacts with a varying number of oxygen atoms of the carbonyl and oxolane ring groups of the nonactin macrocycle. The spectroscopy experiments indicate that the three alkali complexes explored are formed in a S4 conformation. This is in contrast with previous crystallography studies, which concluded that the symmetry of the most stable conformer of the complex changes qualitatively with the cation size, from C2 for Na+ to S4 for K+ and Cs+. Computations with different hybrid density functionals lead to contradictory predictions that appear to be quite sensitive to the modelling of the long range interactions in the coordination arrangements. The stabilization of the nonactin-Na+ complex in the C2 or S4 forms emerges as a subtle feature that may be tuned with an appropriate control of the environmental conditions, and constitutes a challenging benchmark to confront novel computational methods for supramolecular systems.

Correction for ‘Experimental and theoretical investigations of infrared multiple photon dissociation spectra of glutamic acid complexes with Zn2+ and Cd2+’ by Georgia C. Boles et al., Phys. Chem. Chem. Phys., 2017, 19, 12394–12406.

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich. This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively. The infrared (IR) spectrum of the isolated protonated neurotransmitter dopamine was recorded in the fingerprint range (570–1880 cm−1) by means of IR multiple photon dissociation (IRMPD) spectroscopy. The spectrum was obtained in a Fourier transform ion cyclotron resonance mass spectrometer equipped with an electrospray ionization source, which was coupled to a free electron laser (FEL). The spectroscopic studies are complemented by quantum chemical calculations at the B3LYP and MP2 levels of theory using the cc-pVDZ basis set. Several low-energy isomers with protonation occurring at the amino group are predicted in the energy range 0–50 kJ mol−1. Good agreement between the measured IRMPD spectrum and the calculated linear absorption spectra is observed for the two gauche conformers lowest in energy (ΔE) and free energy (ΔG) at both levels of theory, denoted g−1 and g+1. Minor contributions of higher lying gauche isomers cannot be ruled out spectroscopically but their calculated energies suggest only minor population in the sampled ion cloud. In all these gauche structures, one of the three protons of the ammonium group is pointing toward the catechol subunit, thereby maximizing the intramolecular NH–π interaction of the positive charge with the aromatic ring. In total, 16 distinct vibrational bands are observed in the IRMPD spectrum and assigned to individual normal modes of the energetically most stable g−1 conformer, with deviations of less than 24 cm−1 (average 11 cm−1) between measured and calculated frequencies. Comparison with neutral dopamine reveals the effects of protonation on the geometric and electronic structure.

Correction for ‘Zn2+ and Cd2+ cationized serine complexes: infrared multiple photon dissociation spectroscopy and density functional theory investigations’ by Rebecca A. Coates et al., Phys. Chem. Chem. Phys., 2016, 18, 22434–22445.