Molecular Modeling and Simulation: Force Field Development, Evaporation Processes and Thermophysical Properties of Mixtures

To gain physical insight into the behavior of fluids on a microscopic level as well as to broaden the data base for thermophysical properties especially for mixtures, molecular modeling and simulation is utilized in this work. Various methods and applications are discussed, including a procedure for the development of new force field models. The evaporation of liquid nitrogen into a supercritical hydrogen atmosphere is presented as an example for large scale molecular dynamics simulation. System-size dependence and scaling behavior are discussed in the context of Kirkwood-Buff integration. Further, results for thermophysical mixture properties are presented, i.e. the Henry’s law constant of aqueous systems and diffusion coefficients of a ternary mixture

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

The solubility of solids in near-critical fluids. Vi. CHI3 in CO2 revisited

The possibility of a complete thermodynamic description of the behaviour of dilute solutions on the basis of the Krichevskii function J = (∂p/∂x)V,T∞, which performs well in the near-critical region, is hampered by its weak temperature dependence. A previous determination of the solubility of CHI3 in near-critical CO2 showed little change in J over a temperature interval of 30 K. Using a high-pressure spectrophotometric technique, we have re-investigated (CHI3 + CO2), covering the temperature range 273 K to 373 K with seven isotherms. The maximum pressure was 25 MPa and, depending on temperature, the density of CO2 studied was between 0.5 mol · dm-3 and 25 mol · dm-3. As the maximum solubility of CHI3 was 1.7 · 10-2 mol · dm-3 (at the highest temperature and pressure), the solutions were sufficiently dilute to be considered in the Henrian range. The solubility data expressed as ln E, where E is the enhancement factor, were successfully fitted (with the exception of the 305.4 K isotherm) to polynomials of the reduced solvent density and of the square root of the reciprocal reduced temperature. The solubility of CHI3 at low fluid densities was used to obtain information about the intermolecular parameters of the solute using the second virial coefficient limiting expression for ln E. The experimental data allowed reliable estimation of the temperature dependence of J in the whole temperature and pressure ranges studied. The 305.4 K isotherm, which is only 0.4 per cent above the critical temperature of CO2, shows a different dependence on the fluid density, and consequently had to be analysed separately. A careful analysis of the experimental errors suggests that the difference is not an artifact, but is due to the near-critical behaviour of the solvent coupled with the solvent-solute intermolecular interactions

- Synthesis and NMR characterization of meso-ethylene bis(4,7-dimethyl-1-indenyl)zirconium dimethyl.

The new compound meso-ethylenebis (4,7-dimethyl-1-indenyl) zirconium dimethyl (1-Me2) has been prepared and a detailed structural investigation by 2D-NMR has been performed, using COSY gs, NOESY, HBMCgs and HSQCgs spectra. These experiments allowed us to perform the full 1H and 13C NMR spectral assignments. We also detected long distance interactions between the methyl protons on the metal centre and carbon atoms in the indenyl system. A qualitative MO analysis has been performed in order to clarify the experimental evidence

Principle of operation of RotWWC-VSA, a multi-turn rotational variable stiffness actuator

This work presents the principle of operation of RotWWC-VSA, a Variable Stiffness Actuator (VSA) characterized by no rotational stroke limits, conversely to the vast majority of rotational VSAs, typically characterized by restrictions in the angular range of motion. The possibility to perform an unlimited number of turns is a characteristic taken for granted for standard motors, but it is not for VSA rotational motors. It features two antagonist nonlinear equivalent springs, each of them made up of a tension spring, a cam and a wire which, properly configured, realize a torsion spring characterized by a customizable non-linear stiffness characteristic. Theoretical aspects of the actuator are accompanied by numerical simulations. Design guidelines are drawn and a concept design is presented

Synthesis of ring-substituted bis-eta5-cyclopentadienyl derivatives of the Group IV elements containing the bicyclic ligands eta5-C5H3(1,2-CH2-)n, n=4, 5, or 6

The synthesis of unsubstituted and substituted bicyclic eta5-cyclopentadienyl ligands and their Group IV metal complexes [M{eta5-C5H3(1,2-CH2–)n}2Cl2], where n=4, 5, 6 and M=Ti, Zr, Hf, is reported. An example of an ansa-bridged zirconium analogue is also described

A sterically hindered bis-eta-alkylcyclopentadienyl zirconium compound as catalyst for the polymerizaiton of ethene and propene

The compound bis[η-(1,3,3,5,5-pentamethylcyclohexyl)-cyclopentadienyl] zirconium dichloride has been prepared and the crystal structure determined. The compound together with the cocatalyst methylaluminoxane will catalyse the polymerisation of ethene and propene