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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 molecular family of nucleotide triphosphates (NTPs), with adenosine 5′-triphosphate (ATP) as its best-known member, is of high biochemical importance as their phosphodiester bonds form Nature's main means to store and transport energy. Here, gas-phase IR spectroscopic studies and supporting theoretical studies have been performed on adenosine 5′-triphosphate, cytosine 5′-triphosphate and guanosine 5′-triphosphate to elucidate the intrinsic structural properties of NTPs, focusing on the influence of the nucleobase and the extent of deprotonation. Mass spectrometric studies involving collision induced dissociation showed similar fragmentation channels for the three studied NTPs within a selected charge state. The doubly charged anions exhibit fragmentation similar to the energy-releasing hydrolysis reaction in nature, while the singly charged anions show different dominant fragmentation channels, suggesting that the charge state plays a significant role in the favorability of the hydrolysis reaction. A combination of infrared ion spectroscopy and quantum-chemical computations indicates that the singly charged anions of all NTPs are preferentially deprotonated at their β-phosphates, while the doubly-charged anions are dominantly αβ-deprotonated. The assigned three-dimensional structure differs for ATP and CTP on the one hand and GTP on the other, in the sense that ATP and CTP show no interaction between nucleobase and phosphate tail, while in GTP they are hydrogen bonded. This can be rationalized by considering the structure and geometry of the NTPs where the final three dimensional structure depends on a subtle balance between hydrogen bond strength, flexibility and steric hindrance.

The observed variety of metal-ion complexation sites offered by peptides reflects a basic tension between charge solvation of the ion by Lewis-basic chelating groups versus amide nitrogen deprotonation and formation of metal–nitrogen bonds. Gas-phase models of metal-ion coordination can illuminate the factors governing this choice in condensed-phase proteins and enzymes. Here, structures of gas-phase complexes of Ni(II) and Cu(II) with tri- and tetra-peptide ligands are mapped out using a combination of Infrared Multiple Photon Dissociation (IRMPD) spectroscopy and density functional theory (DFT) computations. The two binding modes give distinctive IRMPD signatures, particularly in the diagnostic region 1500–1550 cm−1. Previous observations have suggested that Ni(II) complexes preferentially show the iminol rearrangement pattern (Im) giving low-spin square-planar geometries with metal-ion bonds to deprotonated amide nitrogens. In contrast, alkaline earth metal ion complexes prefer amide carbonyl oxygens chelating the metal ion with pyramidal geometry (charge-solvation, CS). Surprisingly, it is shown here that the Gly4 complexes are CS bound, in contrast with the expectation of Im binding. It is suggested that CS binding is actually a normal Ni(II) and Cu(II) binding mode to simple peptides lacking participating side chains. Three factors are suggested to influence the choice between CS and Im binding patterns: (1) presence of an accessible side-chain Lewis-basic proton interaction site (FGGF, FGG and HAA complexes); (2) short chain length of the peptide leading to a shortage of accessible carbonyl oxygen sites for CS binding, (AAA, FGG and HAA complexes); (3) outright deprotonation of the ligand giving net negatively charged Im[Ni2+(Gly4–3H+)]− and Im[Ni2+(Ala3–3H+)]− complexes, which have a triply-deprotonated ligand. IRMPD spectra of [Cu2+Gly4]2+ and [Cu2+(Gly4–3H+)]− complexes suggest that their structures are similar to their Ni2+ analogs.

Ionic hydrogen bond (IHB) interactions, resulting from the association of ammonia and the two protonated methylxanthine derivatives, caffeine and theophylline, have been characterized using infrared multiphoton dissociation (IRMPD) spectroscopy and electronic structure calculations at the MP2/aug-cc-pVTZ//B3LYP/6-311+G(d,p) level of theory. The proton-bound dimer (PBD) of caffeine and ammonia exhibits a low binding energy and was found to be elusive under the experimental conditions due, most probably, to collision-induced dissociation of the complex with helium buffer gas before IRMPD irradiation. The IRMPD spectrum of a PBD of theophylline and ammonia was obtained and revealed bidentate IHB formation within the complex, which greatly increased the binding energy relative to the most stable isomer of the PBD of caffeine and ammonia. The IRMPD spectra of the protonated forms of caffeine and theophylline have also been obtained. The spectrum of protonated caffeine showed dominant protonation at the N(9) site, whereas the spectrum of protonated theophylline showed a mixture of two isomers. The first protonated isomer of theophylline exhibits protonation at the N(9) site and the second isomer demonstrated protonation at the C(6) carbonyl oxygen. The protonated carbonyl isomer of theophylline cannot be produced as a result of direct protonation and is thus suggested to be a consequence of proton-transport catalysis (PTC) initiated by the electrostatic interaction between water and N(9) protonated theophylline. Calculated anharmonic spectra have been simulated at the B3LYP/6-311+G(d,p) level of theory. It is shown that calculated anharmonic frequencies significantly outperform calculated harmonic frequencies in providing simulated IRMPD spectra in all cases.