Recently, a novel type of multiscale simulation, called Relative Resolution (RelRes), was introduced. In a single system, molecules switch their resolution in terms of their relative separation, with near neighbors interacting via fine-grained potentials yet far neighbors interacting via coarse-grained potentials; notably, these two potentials are analytically parametrized by a multipole approximation. This multiscale approach is consequently able to correctly retrieve across state space the structural and thermal, as well as static and dynamic, behavior of various nonpolar mixtures. Our current work focuses on the practical implementation of RelRes in LAMMPS, specifically for the commonly used Lennard-Jones potential. By examining various correlations and properties of several alkane liquids, including complex solutions of alternate cooligomers and block copolymers, we confirm the validity of this automated LAMMPS algorithm. Most importantly, we demonstrate that this RelRes implementation gains almost an order of magnitude in computational efficiency, as compared with conventional simulations. We thus recommend this novel LAMMPS algorithm for anyone studying systems governed by Lennard-Jones interactions.Accurate prediction of oral pharmacokinetics remains challenging. This study investigated quantitative approaches for the prediction of the area under the plasma concentration-time curve after oral administration (AUCp,oral) to rats using the in vitro-in vivo extrapolation (IVIVE), in silico model using machine learning approaches and the combination of the in silico model and in vitro data. A set of 595 structurally diverse compounds with determined AUCp,oral at 1 mg/kg, in vitro intrinsic clearance (CLint), an unbound fraction in plasma (fu,p) in rats, and kinetic solubility at pH 6.8 was used for this assessment. Prediction models developed by two different types of machine learning techniques (i.e., random forest regression and Gaussian processes) were evaluated using three validation methods implementing the time and cluster-split training and test set and fivefold cross-validation. The developed machine learning models have a square of correlation coefficient (R2) in the range of 0.381-0.685 with 33-45% and in vitro parameters is useful to improve the predictivity of the machine learning model for rat AUCp,oral and supports consideration for predicting AUCp,oral for human and other non-clinical species in a similar manner.The cycloadditions of carbon dioxide into epoxides to afford cyclic carbonates by H-bond donor (HBD) and onium halide (X) cocatalysis have emerged as a key strategy for CO2 fixation. However, if the HBD is also a halide receptor, the two will quench each other, decreasing the catalytic activity. Here, we propose a strained ion pair tris(alkylamino)cyclopropenium halide (TAC·X), in which TAC repels X. TAC possesses a positively charged cyclopropenium core that makes the vicinal C-H or N-H a nonclassical HBD. The interionic strain within TAC·X makes TAC a more electrophilic HBD, allowing it to activate the oxygen of the epoxide and making X more nucleophilic and better able to attack the methylene carbon of the epoxide. NMR titration spectra and computational studies were employed to probe the mechanism of the cycloaddition of CO2 to epoxides reactions under the catalysis of TAC·X. VX-765 in vitro The 1H and 13C1HNMR titration spectra of the catalyst with the epoxide substrate unambiguously confirmed H-bonding between TAC and the epoxide. DFT computational studies identified the transition states in the ring-opening of the epoxide (TS1) and in the ring-closure of the cyclic carbonate (TS2).New drugs to treat tuberculosis (TB) are urgently needed to combat the increase in resistance observed among the current first-line and second-line treatments. Here, we propose ketol-acid reductoisomerase (KARI) as a target for anti-TB drug discovery. Twenty-two analogues of IpOHA, an inhibitor of plant KARI, were evaluated as antimycobacterial agents. The strongest inhibitor of Mycobacterium tuberculosis (Mt) KARI has a Ki value of 19.7 nM, fivefold more potent than IpOHA (Ki = 97.7 nM). This and four other potent analogues are slow- and tight-binding inhibitors of MtKARI. Three compounds were cocrystallized with Staphylococcus aureus KARI and yielded crystals that diffracted to 1.6-2.0 Å resolution. Prodrugs of these compounds possess antimycobacterial activity against H37Rv, a virulent strain of human TB, with the most active compound having an MIC90 of 2.32 ± 0.04 μM. This compound demonstrates a very favorable selectivity window and represents a highly promising lead as an anti-TB agent.A series of 1Hamorphous tri-phenyl pyridine (HAPPY) dyes have been synthesized from luminescent triphenyl-group-containing 2-methyl-6-styryl-substituted-4H-pyran-4-ylidene derivatives in reactions with benzylamine and investigated for suitability as solution-processable light-emitting medium components in thin films for amplified spontaneous emission (ASE). Conversion of a 4H-pyrane ring into a 1H-pyridine fragment enables aggregation-induced emission enhancement (AIEE) behavior in the target products and slightly increases thermal stability, glass transition temperatures, and ASE efficiency with PLQY up to 15% and ASE thresholds as low as 46 μJ/cm2 in neat spin-cast films, although thermal and photophysical properties are mostly dominated by the incorporated electron acceptors. Continued lasing parameter efficiency parameter improvement experiments revealed that no further optimization of HAPPY dyes by doping in polymer matrixes is required as the amplified spontaneous emission thresholds were lowest in pure neat films due to the AIEE phenomenon.Enzymatically degradable polymeric micelles have great potential as drug delivery systems, allowing the selective release of their active cargo at the site of disease. Furthermore, enzymatic degradation of the polymeric nanocarriers facilitates clearance of the delivery system after it has completed its task. While extensive research is dedicated toward the design and study of the enzymatically degradable hydrophobic block, there is limited understanding on how the hydrophilic shell of the micelle can affect the properties of such enzymatically degradable micelles. In this work, we report a systematic head-to-head comparison of well-defined polymeric micelles with different polymeric shells and two types of enzymatically degradable hydrophobic cores. To carry out this direct comparison, we developed a highly modular approach for preparing clickable, spectrally active enzyme-responsive dendrons with adjustable degree of hydrophobicity. The dendrons were linked with three different widely used hydrophilic polymers-poly(ethylene glycol), poly(2-ethyl-2-oxazoline), and poly(acrylic acid) using the CuAAC click reaction.