Reactive molecular dynamics simulations of lithium-ion battery electrolyte degradation.

The development of reliable computational methods for novel battery materials has become essential due to the recently intensified research efforts on more sustainable energy storage materials. Here, we use a recently developed framework allowing to consistently incorporate quantum-mechanical activation barriers to classical molecular dynamics simulations to study the reductive solvent decomposition and formation of the solid electrolyte interphase for a graphite/carbonate electrolyte interface. We focus on deriving condensed-phase effective rates based on the elementary gas-phase reduction and decomposition energy barriers. After a short initial transient limited by the elementary barriers, we observe that the effective rate shows a transition to a kinetically slow regime influenced by the changing coordination environment and the ionic fluxes between the bulk electrolyte and the interface. We also discuss the impact of the decomposition on the ionic mobility. Thus, our work shows how elementary first-principles properties can be mechanistically leveraged to provide fundamental insights into electrochemical stability of battery electrolytes.

[Geriatric Pharmacotherapy in Urology: An Introduction from a Geriatric Pharmacist's Perspective]. / Das Was bedenke, doch mehr bedenke Wie Geriatrische Pharmakotherapie in der Urologie - eine Einführung aus Sicht des geriatrischen Pharmazeuten.

In Germany, too, adverse drug events (ADEs) have been identified as a central problem in the care of geriatric patients. Especially in elderly patients with multimorbidity and increasing frailty, ADEs are among the most frequent and cost-intensive causes of illness in healthcare. In most cases, they are due to drug-related diseases, which necessitate enhanced risk awareness and improved cooperation between physicians, medical specialists, geriatric nurses and pharmacists. In this context, the use of urologic medication for geriatric patients requires particular attention by the consultant.

Solvent Effects on Electronic Excitations of an Organic Chromophore.

In this work we study the solvatochromic shift of a selected low-energy excited state of alizarin in water by using a linear-scaling implementation of large-scale time-dependent density functional theory (TDDFT). While alizarin, a small organic dye, is chosen as a simple example of solute-solvent interactions, the findings presented here have wider ramifications for the realistic modeling of dyes, paints, and pigment-protein complexes. We find that about 380 molecules of explicit water need to be considered in order to yield an accurate representation of the solute-solvent interaction and a reliable solvatochromic shift. By using a novel method of constraining the TDDFT excitation vector, we confirm that the origin of the slow convergence of the solvatochromic shift with system size is due to two different effects. The first factor is a strong redshift of the excitation due to an explicit delocalization of a small fraction of the electron and the hole from the alizarin onto the water, which is mainly confined to within a distance of 7 Å from the alizarin molecule. The second factor can be identified as long-range electrostatic influences of water molecules beyond the 7 Å region on the ground-state properties of alizarin. We also show that these electrostatic influences are not well reproduced by a QM/MM model, suggesting that full QM studies of relatively large systems may be necessary in order to obtain reliable results.

Flow sensing by pinniped whiskers.

Beside their haptic function, vibrissae of harbour seals (Phocidae) and California sea lions (Otariidae) both represent highly sensitive hydrodynamic receptor systems, although their vibrissal hair shafts differ considerably in structure. To quantify the sensory performance of both hair types, isolated single whiskers were used to measure vortex shedding frequencies produced in the wake of a cylinder immersed in a rotational flow tank. These measurements revealed that both whisker types were able to detect the vortex shedding frequency but differed considerably with respect to the signal-to-noise ratio (SNR). While the signal detected by sea lion whiskers was substantially corrupted by noise, harbour seal whiskers showed a higher SNR with largely reduced noise. However, further analysis revealed that in sea lion whiskers, each noise signal contained a dominant frequency suggested to function as a characteristic carrier signal. While in harbour seal whiskers the unique surface structure explains its high sensitivity, this more or less steady fundamental frequency might represent the mechanism underlying hydrodynamic reception in the fast swimming sea lion by being modulated in response to hydrodynamic stimuli impinging on the hair.

Why sliding friction of Ne and Kr monolayers is so different on the Pb(111) surface.

To understand the tribological properties of Ne and Kr on Pb(111), the potential energy surfaces for sliding motion of Ne, Kr, and Xe monolayers on the Pb(111) surface are examined through density functional calculations, using either local density or self-consistent nonlocal van der Waals functionals. The calculated adsorption energy for Xe/Pb(111) agrees well with experiment, validating the present approach and parameters. Activation energies along a sliding path indicate that Ne motion is much faster than Kr and Xe on Pb(111) at T∼6 K, which explains the puzzling experimental observation.

Conformational transitions in single polymer molecules modeled with a complete energy landscape: continuous two-state model.

An extension of the two-state Freely Jointed Chain model is presented in which the discrete energies of the two conformers are replaced by continuous functions of the conformer length. The statistical mechanics is initially developed in the Gibbs ensemble and leads to a conformational multi-state model. This is used to fit the equilibrium force-extension curve for Dextran. The continuous model also allows the use of Transfer Matrix methods to calculate all statistical properties in the Helmholtz ensemble, including thermal fluctuations. The latter are obtained with near perfect agreement to experiment.

Characterization of oral sustained release preparations of iloprost in a pig model by plasma level monitoring.

Iloprost (5-[(E)-1S,5S,6R,7R)-7-hydroxy-6-[(E)-3S,4RS)-3-hydroxy-4- methyl-octen-6-inyl]-bicyclo[3.3.0]-oct-3-ylidene)-pentanoic acid) is a chemically stable PGI2-mimetic with high pharmacological potency. Therapeutic efficacy in various disease stages (e.g. peripheral arterial occlusive disease, M. Raynaud and thromboangiitis obliterans) was shown after repeated once-a-day infusion treatment over several weeks. In order to facilitate drug therapy an oral dosage form is desirable. As a first step, a suitable animal model was needed to screen several formulation variants prior to characterization of promising candidates in man. After intravenous infusion treatment, the pig exhibited - similar to man - strictly dose-dependent steady state plasma levels and a total iloprost clearance of approximately 26 ml/min/kg (man approximately 20 ml/min/kg). Partial similarity of physiology and anatomy of the GI-tract and the possibility to administer intact capsule dosage forms led to a series of screen experiments with several sustained release preparations (pellets and matrix tablets) of iloprost exhibiting different in-vitro drug release profiles. A good correlation of in-vitro dissolution and in vivo plasma level data was obtained for all preparations containing the pellet neutral polymer. For the other formulations slight differences between duration of liberation and plasma level or time of maximum dissolution rate and tmax of plasma levels was observed. In the case of ionized polymers or matrix tablets, in vitro dissolution profiles were slightly different from in vivo data. This might be due to different dissolution behaviour in the gastro-intestinal tract. The pig seems to be a model that is suitable for verifying drug liberation profile in-vivo. Based upon plasma levels obtained in animals, selection of a formulation for characterization in man can be made.

Oral iloprost in healthy volunteers.

Iloprost is a potent chemically stable PGI2-mimetic. Therapeutic efficacy was shown after i.v. infusion treatment in several states of peripheral vascular disease. For out-patient therapy an oral dosage form should be developed. Based upon dissolution profiles and in vivo data of a pig model, three different film-coated pellet formulations were selected for pharmacokinetic characterization in nine healthy volunteers. In the first part of the study groups of three test subjects were treated with increasing dosages (150-300 micrograms) of iloprost. At 300 micrograms flush and headache led to the discontinuation of those titration. All formulations exhibited dose-dependent serum level profiles. The cross-over characterization in all test subjects showed that one formulation, which exhibited a modified in vitro dissolution of 60% of the dose within 1 h in pH 7.4 phosphate buffer, was optimal from the pharmacokinetic profile. After oral administration of this formulation the bioavailable dose fraction was highest and half-maximal serum levels lasted for 2.4 h (mean); therapeutic serum levels were maintained for 2.1-5.0 h. This formulation was chosen for further investigation to imitate therapeutic serum level profiles as obtained after i.v. infusion for 4-6 h with a once-a-day dosage form.

In-vitro and in-vivo characterisation of two sustained release formulations for the antidepressant rolipram.

Using the pellet technology two sustained release formulations for (dl)-rolipram (ZK 62 711; CAS 61413-54-5) were developed and characterised by in-vitro dissolution tests and in a cross-over study in healthy male volunteers. In-vitro, 50% release was achieved within 2.5 h for formulation A and within 4 h for B. In-vivo, Cmax values of 4.4 +/- 0.9 ng/ml (A) and 2.1 +/- 0.8 ng/ml (B) were observed 2.8 +/- 0.8 h or 10.3 +/- 3.7 h after oral intake of 3 mg (dl)-rolipram. The terminal disposition half-life in the plasma was similar for both formulations (12 +/- 13 h and 11 +/- 2 h). Expectedly, the relative bioavailability of formulation B was lower compared to A (72%). Using the pellet technology, formulations with an intended release profile can be tailored to suit by mixing pellets with different release characteristics within one dosage form.