The effect of the condensed-phase environment on the vibrational frequency shift of a hydrogen molecule inside clathrate hydrates.

We report a theoretical study of the frequency shift (redshift) of the stretching fundamental transition of an H2 molecule confined inside the small dodecahedral cage of the structure II clathrate hydrate and its dependence on the condensed-phase environment. In order to determine how much the hydrate water molecules beyond the confining small cage contribute to the vibrational frequency shift, quantum five-dimensional (5D) calculations of the coupled translation-rotation eigenstates are performed for H2 in the v=0 and v=1 vibrational states inside spherical clathrate hydrate domains of increasing radius and a growing number of water molecules, ranging from 20 for the isolated small cage to over 1900. In these calculations, both H2 and the water domains are treated as rigid. The 5D intermolecular potential energy surface (PES) of H2 inside a hydrate domain is assumed to be pairwise additive. The H2-H2O pair interaction, represented by the 5D (rigid monomer) PES that depends on the vibrational state of H2, v=0 or v=1, is derived from the high-quality ab initio full-dimensional (9D) PES of the H2-H2O complex [P. Valiron et al., J. Chem. Phys. 129, 134306 (2008)]. The H2 vibrational frequency shift calculated for the largest clathrate domain considered, which mimics the condensed-phase environment, is about 10% larger in magnitude than that obtained by taking into account only the small cage. The calculated splittings of the translational fundamental of H2 change very little with the domain size, unlike the H2 j = 1 rotational splittings that decrease significantly as the domain size increases. The changes in both the vibrational frequency shift and the j = 1 rotational splitting due to the condensed-phase effects arise predominantly from the H2O molecules in the first three complete hydration shells around H2.

Preemptive warfarin dose reduction after initiation of sulfamethoxazole-trimethoprim or metronidazole.

To evaluate the utility of a preemptive warfarin dose reduction at the time of initiation of either sulfamethoxazole-trimethoprim or metronidazole, a retrospective chart review of patients who received an outpatient prescription for warfarin and either sulfamethoxazole-trimethoprim and/or metronidazole from July 1, 2011 to July 1, 2015 was conducted. Clinical outcomes compared Veterans who had a warfarin dose reduction and those who did not within 120 h (5 days) of antibiotic initiation. The primary outcome compared the pre-and post-antibiotic International Normalized Ratio (INR) of patients in the intervention group (warfarin dose reduction) with those in the control group (no intervention). Secondary outcomes assessed incidence of thromboembolic and major bleeding events within 30 days of antibiotic completion. Fifty patients were assessed. Forty-nine patients had at least one follow-up appointment; 126 follow-up visits were evaluated. There was a statistically significant difference for the change in therapeutic INR at the first follow-up appointment (p = 0.029) for those patients in the control group. On average, the patients in the intervention group required fewer follow-up visits (p = 0.019). There were no statistically significant differences for the overall rate of therapeutic INR values between groups, as well as no instances of a thromboembolic or major bleeding events during the follow-up period. Clinically significant differences were observed for patients who received a preemptive warfarin dose reduction upon initiation of sulfamethoxazole-trimethoprim or metronidazole. Patients in the intervention group required fewer follow-up appointments and were more likely maintain a therapeutic INR within the 30 days following the antibiotic course. Results of this study will be presented the at Pharmacy and Therapeutics committee in an effort to seek approval for policy development to initiate a local preemptive warfarin dose adjustment as a standard of practice.

Competing quantum effects in the free energy profiles and diffusion rates of hydrogen and deuterium molecules through clathrate hydrates.

Clathrate hydrates hold considerable promise as safe and economical materials for hydrogen storage. Here we present a quantum mechanical study of H2 and D2 diffusion through a hexagonal face shared by two large cages of clathrate hydrates over a wide range of temperatures. Path integral molecular dynamics simulations are used to compute the free-energy profiles for the diffusion of H2 and D2 as a function of temperature. Ring polymer molecular dynamics rate theory, incorporating both exact quantum statistics and approximate quantum dynamical effects, is utilized in the calculations of the H2 and D2 diffusion rates in a broad temperature interval. We find that the shape of the quantum free-energy profiles and their height relative to the classical free energy barriers at a given temperature, as well as the rate of diffusion, are strongly affected by competing quantum effects: above 25 K, zero-point energy (ZPE) perpendicular to the reaction path for diffusion between cavities decreases the quantum rate compared to the classical rate, whereas at lower temperatures tunneling outcompetes the ZPE and as a result the quantum rate is greater than the classical rate.

Impact of the Condensed-Phase Environment on the Translation-Rotation Eigenstates and Spectra of a Hydrogen Molecule in Clathrate Hydrates.

We systematically investigate the manifestations of the condensed-phase environment of the structure II clathrate hydrate in the translation-rotation (TR) dynamics and the inelastic neutron scattering (INS) spectra of an H2 molecule confined in the small dodecahedral cage of the hydrate. The aim is to elucidate the extent to which these properties are affected by the clathrate water molecules beyond the confining cage and the proton disorder of the water framework. For this purpose, quantum calculations of the TR eigenstates and INS spectra are performed for H2 inside spherical clathrate domains of gradually increasing radius and the number of water molecules ranging from 20 for the isolated small cage to more than 1800. For each domain size, several hundred distinct hydrogen-bonding topologies are constructed in order to simulate the effects of the proton disorder. Our study reveals that the clathrate-induced splittings of the j = 1 rotational level and the translational fundamental of the guest H2 are influenced by the condensed-phase environment to a dramatically different degree, the former very strongly and the latter only weakly.

The HD molecule in small and medium cages of clathrate hydrates: quantum dynamics studied by neutron scattering measurements and computation.

We report inelastic neutron scattering (INS) measurements on molecular hydrogen deuteride (HD) trapped in binary cubic (sII) and hexagonal (sH) clathrate hydrates, performed at low temperature using two different neutron spectrometers in order to probe both energy and momentum transfer. The INS spectra of binary clathrate samples exhibit a rich structure containing sharp bands arising from both the rotational transitions and the rattling modes of the guest molecule. For the clathrates with sII structure, there is a very good agreement with the rigorous fully quantum simulations which account for the subtle effects of the anisotropy, angular and radial, of the host cage on the HD microscopic dynamics. The sH clathrate sample presents a much greater challenge, due to the uncertainties regarding the crystal structure, which is known only for similar crystals with different promoter, but nor for HD (or H2) plus methyl tert-butyl ether (MTBE-d12).

Experimental inelastic neutron scattering spectrum of hydrogen hexagonal clathrate-hydrate compared with rigorous quantum simulations.

We have performed high-resolution inelastic neutron scattering (INS) measurements on binary hydrogen clathrate hydrates exhibiting the hexagonal structure (sH). Two samples, differing only in the ortho/para fraction of hydrogen, were prepared using heavy water and methyl tert-butyl ether as the promoter in its perdeuterated form. The INS spectrum of the translation-rotation (TR) excitations of the guest H2 molecule was obtained by subtracting the very weak signal due to the D2O lattice modes. By means of a subtraction procedure, it has been possible to obtain separately the spectra of caged p-H2 and o-H2. sH clathrates are comprised of three distinct types of cages, two of which, differing in shape and size, are each occupied by one H2 molecule only. Both contribute to the measured INS spectrum which is, therefore, rather complex and challenging to assign unambiguously. To assist with the interpretation, the INS spectra are calculated accurately utilizing the quantum methodology which incorporates the coupled five-dimensional TR energy levels and wave functions of the H2 molecule confined in each type of nanocage. The computed INS spectra are highly realistic and reflect the complexity of the coupled TR dynamics of the guest H2 in the anisotropic confining environment. The simulated INS spectra of p-H2 and o-H2 in the small and medium cages are compared with the experimental data, and are indispensable for their interpretation.

Inelastic neutron scattering spectrum of H2@C60 and its temperature dependence decoded using rigorous quantum calculations and a new selection rule.

In the supramolecular complex H2@C60, the lightest of molecules, H2, is encapsulated inside the most highly symmetric molecule C60. The elegance and apparent simplicity of H2@C60 conceal highly intricate quantum dynamics of the coupled translational and rotational motions of the guest molecule in a nearly spherical nanoscale cavity, which embodies some of the most fundamental concepts of quantum mechanics. Here we present the first rigorous and highly accurate quantum calculations of the inelastic neutron scattering (INS) spectra of this prototypical endohedral fullerene complex and their temperature dependence. The calculations enable complete assignment of the recently reported experimental INS spectra of H2@C60 measured at several temperatures. We also derive a new and unexpected selection rule for the INS spectroscopy of H2 in a near-spherical confinement, which explains why the INS transitions between certain translation-rotation eigenstates of H2 in C60 have zero intensity and do not appear in the spectra.