With renewed interest in free energy methods in contemporary structure-based drug design there is a pressing need to validate against multiple targets and force fields to assess the overall ability of these methods to accurately predict relative binding free energies. We computed relative binding free energies using GPU accelerated Thermodynamic Integration (GPU-TI) on a dataset originally assembled by Schrödinger, Inc.. Using their GPU free energy code (FEP+) and the OPLS2.1 force field combined with the REST2 enhanced sampling approach, these authors obtained an overall MUE of 0.9 kcal/mol and an overall RMSD of 1.14 kcal/mol. In our study using GPU-TI from AMBER with the AMBER14SB/GAFF1.8 force field but without enhanced sampling, we obtained an overall MUE of 1.17 kcal/mol and an overall RMSD of 1.50 kcal/mol for the 330 perturbations contained in this data set. A more detailed analyses of our results suggested that the observed differences between the two studies arise from differences in sampling protocols along with differences in the force fields employed. Future work should address the problem of establishing benchmark quality results with robust statistical error bars obtained through multiple independent runs and enhanced sampling, which is possible with the GPU-accelerated features in AMBER.

The direct transformation of cellulose, which is the main component of lignocellulosic biomass, into building-block chemicals is the key to establishing biomass-based sustainable chemical processes. Only limited successes have been achieved for such transformations under mild conditions. Here we report the simple and efficient chemocatalytic conversion of cellulose in water in the presence of dilute lead(II) ions, into lactic acid, which is a high-value chemical used for the production of fine chemicals and biodegradable plastics. The lactic acid yield from microcrystalline cellulose and several lignocellulose-based raw biomasses is 460% at 463 K. Both theoretical and experimental studies suggest that lead(II) in combination with water catalyses a series of cascading steps for lactic acid formation, including the isomerization of glucose formed via the hydrolysis of cellulose into fructose, the selective cleavage of the C3-C4 bond of fructose to trioses and the selective conversion of trioses into lactic acid.

Conformation-induced volatile and nonvolatile conductance switching effects were demonstrated in non-conjugated polymers containing the same electroactive pendant groups. Single-layer devices of the structure indium-tin-oxide/polymer/aluminum were fabricated from two non-conjugated polymers with pendant carbazole groups in different spacer units. The device based on poly(2-(N-carbazolyl)ethyl methacrylate) (PMCz) exhibited nonvolatile write-once-read-many-times (WORM) memory behavior with an ON/OFF current ratio up to 106, while the device based on poly(9-(2-((4-vinylbenzyl)oxy)ethyl)-9H-carbazole) (PVBCz) exhibited volatile memory behavior with an ON/OFF current ratio of approximately 103. The formation of carbazole excimers resulting from conformation-induced conductance switching under an electric field was revealed in situ by fluorescence spectroscopy. The corresponding voltage-induced conformation ordering in the polymer film was captured by transmission electron microscopy. In the absence of a spacer unit between the pendant carbazole group and the main chain, regioregular poly(N-vinylcarbazole) (PVK) exhibited only one conductivity state (ON state). The differences in memory behavior among the three polymers were attributed to their inherent differences in the degree of regioregularity and ease of conformational relaxation of the field-induced regioregular carbazole groups. These conformational effects were in turn dictated by the chemical structure and steric effect of the spacer unit between the pendant carbazole group and the main chain.

Electronic memory devices having the indium-tin oxide/polymer/Al sandwich structure were fabricated from polymers containing pendant azobenzene chromophores in donor-acceptor structures. The reversibility, or rewritability, of the high-conductivity (ON) state was found to be dependent on the terminal moiety of the azobenzene chromophore. While the polymers with electron-accepting terminal moieties (-Br or -NO2) in the pendant azobenzene exhibit write-once, read-many-times (WORM) type memory behavior, those with electron-donating terminal moieties (-OCH3) exhibit rewritable (FLASH) memory behavior. The WORM memory devices have low switching ("write") voltages below -2 V and high ON/OFF current ratios of about 10(4)-10(6). The polarity of the "write" voltage can be reversed by using an electrode with a higher work function than Al, thus excluding metallic filamentary conduction as a cause of the bistable switching phenomenon. The FLASH memory devices have low "write" and "erase" voltages of about -1.7 to -1.8 V and 2.0 to 2.2 V, respectively, and ON/OFF current ratios of about 10(3)-10(4). The electrical bistability observed can be attributed to charge trapping at the azobenzene chromophores, resulting in the charge-separated, high-conductivity state. The proposed mechanism is supported experimentally by a red shift and peak broadening in the UV-visible absorption spectra of the polymer films resulting from the OFF-to-ON electrical transition.