Spectroscopic Signatures of Hydrogen-Bonding Motifs in Protonic Ionic Liquid Systems: Insights from Diethylammonium Nitrate in the Solid State.

Diethylammonium nitrate, [N0 0 2 2][NO3], and its perdeuterated analogue, [N D D 2 2] [NO3], were structurally characterized and studied by infrared, Raman, and inelastic neutron scattering (INS) spectroscopy. Using these experimental data along with state-of-the-art computational materials modeling, we report unambiguous spectroscopic signatures of hydrogen-bonding interactions between the two counterions. An exhaustive assignment of the spectral features observed with each technique has been provided, and a number of distinct modes related to NH···O dynamics have been identified. We put a particular emphasis on a detailed interpretation of the high-resolution, broadband INS experiments. In particular, the INS data highlight the importance of conformational degrees of freedom within the alkyl chains, a ubiquitous feature of ionic liquid (IL) systems. These findings also enable an in-depth physicochemical understanding of protonic IL systems, a first and necessary step to the tailoring of hydrogen-bonding networks in this important class of materials.

A molecular view of cisplatin's mode of action: interplay with DNA bases and acquired resistance.

The interaction of the widely used anticancer drug cisplatin with DNA bases was studied by EXAFS and vibrational spectroscopy (FTIR, Raman and INS), coupled with DFT/plane-wave calculations. Detailed information was obtained on the local atomic structure around the Pt(ii) centre, both in the cisplatin-purine (adenine and guanine) and cisplatin-glutathione adducts. Simultaneous neutron and Raman scattering experiments allowed us to obtain a reliable and definite picture of this cisplatin interplay with its main pharmacological target (DNA), at the molecular level. The vibrational experimental spectra were fully assigned in the light of the calculated pattern for the most favoured geometry of each drug-purine adduct, and cisplatin's preference for guanine (G) relative to adenine (A) within the DNA double helix was experimentally verified: a complete N by S substitution in the metal coordination sphere was only observed for [cDDP-A2], reflecting a somewhat weaker Pt-A binding relative to Pt-G. The role of glutathione on the drug's pharmacokinetics, as well as on the stability of platinated DNA adducts, was evaluated as this is the basis for glutathione-mediated intracellular drug scavenging and in vivo resistance to Pt-based anticancer drugs. Spectroscopic evidence of the metal's preference for glutathione's sulfur over purine's nitrogen binding sites was gathered, at least two sulfur atoms being detected in platinum's first coordination sphere.

Polymorphism in cisplatin anticancer drug.

This study reports a combined experimental and theoretical study of the solid-state polymorphism of the anticancer agent cisplatin. A complete assignment was performed for the inelastic neutron scattering (INS) and Raman spectra collected simultaneously for cisplatin, at different temperatures, with a view to obtain reliable and definitive evidence of the relative thermal stability of its α and ß polymorphic species. A marked temperature-dependent hysteresis was observed, as previously reported in the literature. Theoretical calculations were carried out at the density functional theory level, using a plane-wave basis set approach and pseudopotentials. A detailed comparison with the experimental Raman and INS data showed that the α polymorph is present at the lowest temperatures, whereas the ß form occurs near room temperature. Furthermore, regions of coexistence of both forms are identified, which depend on the working mode (heating or cooling). These findings imply that Raman spectroscopy allows clear identification of the α and ß polymorphs at a given temperature and can unambiguously discriminate between them. Elucidation of the polymorphic equilibrium of this widely used anticancer drug is paramount for its pharmaceutical preparation and storage conditions.

Comment on: "Comparative vibrational analysis of 1,2-dinitrobenzene and 1-fluoro-3-nitrobenzene" by S Ramalingam, S. Periandy et al. [Spectrochim. Acta A 84 (2011) 86-98].

The title paper reports, inter alia, the ab initio calculated structure and vibrational spectra of 1,2-dinitrobenzene. The calculated structure of the dinitrobenzene is wrong. We have recalculated the ab initio structure and assigned the spectra in agreement with previously published work.

Exploiting the quasi-invariance of atomic displacements.

The quasi-invariance of the magnitude of atomic displacements is briefly introduced and demonstrated for the case of indole. The usefulness of this property for the assignment of neutron vibrational spectra is underlined.

Inelastic neutron scattering study of Pt(II) complexes displaying anticancer properties.

The well-known platinum(II) chemotherapeutic drugs cisplatin [cis-(NH(3))(2)PtCl(2)] and carboplatin [Pt(NH(3))(2)C(6)O(4)H(6)], as well as the analogous transplatin [trans-(NH(3))(2)PtCl(2)], were studied by inelastic neutron scattering (INS) spectroscopy, coupled to quantum mechanical methods, and some ancillary work with X-ray diffraction on powders. An assignment of the experimental spectra was carried out based on the calculated INS transition frequencies and intensities (at the DFT level), thereby achieving a good correspondence between the calculated and observed data. Unusually good-quality INS spectra were obtained from about 250 mg, which is the smallest sample of a hydrogenous compound for which a successful INS interpretation has been reported. The knowledge of the local configuration of this kind of complexes is essential for an accurate understanding of their activity, which will pave the way for the rational design of novel third-generation drugs comprising cisplatin- and carboplatin-like moieties.

Gelation or molecular recognition; is the bis-(α,ß-dihydroxy ester)s motif an omnigelator?

Understanding the gelation of liquids by low molecular weight solutes at low concentrations gives an insight into many molecular recognition phenomena and also offers a simple route to modifying the physical properties of the liquid. Bis-(α,ß-dihydroxy ester)s are shown here to gel thermoreversibly a wide range of solvents, raising interesting questions as to the mechanism of gelation. At gelator concentrations of 5-50 mg ml⁻¹, gels were successfully formed in acetone, ethanol/water mixtures, toluene, cyclohexane and chloroform (the latter, albeit at a higher gelator concentration). A range of neutron techniques - in particular small-angle neutron scattering (SANS) - have been employed to probe the structure of a selection of these gels. The universality of gelation in a range of solvent types suggests the gelation mechanism is a feature of the bis-(α,ß-dihydroxy ester) motif, with SANS demonstrating the presence of regular structures in the 30-40 Å range. A correlation between the apparent rodlike character of the structures formed and the polarity of the solvent is evident. Preliminary spin-echo neutron scattering studies (SESANS) indicated the absence of any larger scale structures. Inelastic neutron spectroscopy (INS) studies demonstrated that the solvent is largely unaffected by gelation, but does reveal insights into the thermal history of the samples. Further neutron studies of this kind (particularly SESANS and INS) are warranted, and it is hoped that this work will stimulate others to pursue this line of research.

Vibrational spectra of benzene chromium tricarbonyl and its mesityl analogue: a study by neutron spectroscopy.

We have used high resolution neutron vibrational spectroscopy to study the vibrations of the model compound for arene-to-metal bonding, benzene chromium tricarbonyl, and its mesityl analogue. It is shown that all previously published assignment schemes, based on optical spectroscopy alone, are wrong, and new assignments are given in agreement with ab initio calculations.

Comment on: "FTIR and FTRaman spectra, assignments, ab initio HF and DFT analysis of 4-nitrotoluene" by S. Ramalingam et al., Spectrochemica Acta A 75 (2010) 1308-1314.

The title paper reports the ab initio calculated structure and vibrational spectra of 4-nitrotoluene. The calculated structure is wrong and the assignments are inconsistent with earlier work. We have recalculated the ab initio structure and reassigned the spectra in agreement with the standard text.

Hydrogen-bond dynamics of C-H...O interactions: the chloroform...acetone case.

Spectroscopic evidence for C-H...O hydrogen bonding in chloroform...acetone [Cl(3)CH...O=C(CH(3))(2)] mixtures was obtained from vibrational inelastic neutron scattering (INS) spectra. Comparison between the INS spectra of pure samples and their binary mixtures reveals the presence of new bands at about 82, 130 and 170 cm(-1). Assignment of the 82 cm(-1) band to the nuO...H anti-translational mode is considered and discussed. In addition, the betaC-H mode of CHCl(3) at 1242 cm(-1) is split in the spectra of the mixtures, and the high-wavenumber component is assigned to the hydrogen-bonded complex. The plot of the integrated intensity of this component shows a maximum for x=0.5, in agreement with the 1:1 stoichiometry of the chloroformacetone complex, with a calculated complexation constant of 0.15 dm(3) mol(-1). Results also show that the complex behaves as an independent entity, that is, despite being weak, such interactions play a key role in supramolecular chemistry.

No evidence for Evans' holes in the A, B, C vibrational structure of potassium dihydrogen arsenate.

We have used inelastic neutron scattering (INS) spectroscopy to study the "A, B, C" region of the hydrogen bond in potassium dihydrogen arsenate. The broad spectral feature observed in infrared spectroscopy is shown to be associated with a ridge of constant intensity in the INS, which follows the recoil line for a unit-mass particle. The onset energy of the ridge is unclear but, we believe, is associated with the optical "C" feature at 1610 cm(-1), and which we assign to nu(O-H). The "B" and "A" optical bands were both demonstrated to be two-quantum events and are, thus, not associated with the fundamental nu(O-H). They are readily assigned to the harmonic overtone delta(OH)(0-2) and the combination gamma(OH)(0-1)+delta(OH)(0-1), which both sit astride the ridge and there is no evidence for Evans' holes. The other overtone, gamma(OH)(0-2), has been assigned to a very weak feature, observed for the first time at 1900 cm(-1). A simple model was used to describe the intensity distributions.

Comment on: "FTIR, FT-Raman, scaled quantum chemical studies of the structure and vibrational spectra of 1,5-dinitronaphthalene" by Arivazhaga et al. [Spectrochim. Acta A72 (2009) 941-946].

The title paper [1] reports ab initio calculations of the structure and molecular vibrations of 1,5-dinitronaphthalene. The calculations are unminimised, the molecular structure is wrong and the vibrational spectra are misinterpreted. These errors have been corrected and the vibrational spectra of 1,5-dinitronaphthalene have been reassigned in agreement with the optical and neutron spectroscopic data.

A neutron scattering study of strong-symmetric hydrogen bonds in potassium and cesium hydrogen bistrifluoroacetates: Determination of the crystal structures and of the single-well potentials for protons.

The crystal structures of potassium and cesium bistrifluoroacetates, KH(CF(3)COO)(2) and CsH(CF(3)COO)(2), respectively, were determined at room and cryogenic temperatures with the single crystal neutron diffraction technique. The crystals belong to the monoclinic space groups, I2a and A2a, respectively, and there is no evidence of any structural phase transition. In both crystals, trifluoroacetate entities in centrosymmetric dimers are linked by very short hydrogen bonds lying across a center of inversion. The thermal parameters provide no evidence of any double minimum potential for hydrogen bond protons. Single-minimum potentials were determined via best fitting to the inelastic neutron scattering spectral profiles of the stretching vibrations. They comprise a narrow well for the ground state and a very broad quasiharmonic well for excited states. The spread out of the wave functions of these states shows that protons are no longer confined between the oxygens. Presumably, they are attracted by the lone pairs of oxygen atoms. These potentials emphasize the covalent nature of the OO bond and the ionic character of the hydrogen bond proton.

Transverse acoustic modes of biogenic and alpha,omega-polyamines: a study by inelastic neutron scattering and Raman spectroscopies coupled to DFT calculations.

A complete analysis of the transverse acoustic modes (TAMs) for the homologous series of alpha,omega-diamines (H2N(CH2)nNH2) (n = 2-10, n = 12) as well as for the biogenic polyamines spermidine and spermine was undertaken, by Raman and inelastic neutron scattering (INS) spectroscopies combined with density functional theory (DFT) calculations. A complete assignment of the whole set of TAMs was carried out, for both the undeuterated and N-deuterated species. 1,2-Diaminoethane was found to display exceptional behavior, probably due to the formation of dimers in the solid state. An n-even/n-odd dependence of the low frequency INS pattern was observed for these polyamines. The very good accordance between their INS experimental TAMs and the ones previously reported for the corresponding n-alkanes suggest a close conformational similarity between these systems.

Drug-excipient interactions in ketoprofen: a vibrational spectroscopy study.

Ketoprofen (3-benzoyl-alpha-methylbenzeneacetic acid) is a widely used nonsteroidal anti-inflammatory drug (NSAID), always administered in the form of drug-excipient physical mixtures (PMs). The occurrence of possible interactions between ketoprofen and two commonly used excipients-lactose (LAC) and polyvinylpyrrolidone (PVP)-was evaluated, through vibrational spectroscopy techniques [both Raman and Inelastic Neutron Scattering (INS)]. Spectral evidence of drug:excipient close contacts, which were enhanced by aging, was verified for the (1:1) (w:w) (ketoprofen:PVP) and (ketoprofen:LAC) PMs, both by Raman and INS. These interactions were found to involve mainly the central carbonyl and the terminal methyl-carboxylic moieties of the ketoprofen molecule, this being reflected in particular vibrational modes, such as the methyl torsion, the out-of-plane C-OH bending, and the inter-ring C=O stretching.