Chameleonic properties, i. e., the capacity of a molecule to hide polarity in non-polar environments and expose it in water, help achieving sufficient permeability and solubility for drug molecules with high MW. We present models of experimental measures of polarity for a set of 24 FDA approved drugs (MW 405-1113) and one PROTAC (MW 1034). Conformational ensembles in aqueous and non-polar environments were generated using molecular dynamics. A linear regression model that predicts chromatographic apparent polarity (EPSA) with a mean unsigned error of 10 Å2 was derived based on separate terms for donor, acceptor, and total molecular SASA. A good correlation (R2=0.92) with an experimental measure of hydrogen bond donor potential, Δlog Poct-tol, was found for the mean hydrogen bond donor SASA of the conformational ensemble scaled with Abraham's A hydrogen bond acidity. Two quantitative measures of chameleonic behaviour, the chameleonic efficiency indices, are introduced. We envision that the methods presented herein will be useful to triage designed molecules and prioritize those with the best chance of achieving acceptable permeability and solubility. 相似文献
Chemistry and Technology of Fuels and Oils - When a reservoir is subjected to long-term water and polymer flooding, the formed preferential flow paths are widely distributed in the formation, and... 相似文献
ITO/Ag/ITO multilayer thin films have been a potential substitute of the conventional single-layer transparent conducting film. Nevertheless, the mechanical stability under preparation and in-service conditions still limits their applications and developments. In this paper, the influences of different structural properties as well as layer structure on both surface morphological properties and mechanical properties of the ITO/Ag/ITO multilayer thin films in comparison with commercial single-layer ITO thin film were systematically investigated. The results demonstrate that, i) the tri-layer composite has large impacts on the preferential orientation, and exhibits the decreased values of surface roughness, net lattice distortion and residual stress; ii) the increased hardness (H) and decreased Young's modulus (E) for full annealed ITO/Ag/ITO multilayer films indicate that it is possible to tailor mechanical properties of the materials by manufacturing multilayer composite; iii) the ITO/Ag/ITO multilayer thin film exhibits remarkable improvements in wear resistance with the increase of annealing temperature, which is mainly attributed to the increased ratios of H/E and H3/E2. 相似文献
The traction motor is the power source of the locomotive. If the surface waviness occurs on the races of the motor bearing, it will cause abnormal vibration and noise, accelerate fatigue and wear, and seriously affect the stability and safety of the traction power transmission. In this paper, an excitation model coupling the time-varying displacement and contact stiffness excitations is adopted to investigate the effect of the surface waviness of the motor bearing on the traction motor under the excitation from the locomotive-track coupled system. The detailed mechanical power transmission path and the internal/external excitations (e.g., wheel–rail interaction, gear mesh, and internal interactions of the rolling bearing) of the locomotive are comprehensively considered to provide accurate dynamic loads for the traction motor. Effects of the wavenumber and amplitude of the surface waviness on the traction motor and its neighbor components of the locomotive are investigated. The results indicate that controlling the amplitude of the waviness and avoiding the wavenumber being an integer multiple of the number of the rollers are helpful for reducing the abnormal vibration and noise of the traction motor.