Due to their important role in many diseases, cysteine proteases represent new promising drug targets. An important class of cysteine-protease inhibitors is derived from the naturally occurring compound E64, possessing an epoxysuccinyl moiety as warhead. Experimental studies show stereoselectivity concerning the inhibition potency, e.g., a trans-configured epoxide ring is essential for inhibition, and furthermore, in most cases, the ( S, S)-configured inhibitors have a higher inhibition potency than their ( R, R)-counterparts. However, the underlying effects are not fully understood. In this work, such effects are investigated by classical molecular dynamics simulations and combined quantum mechanics/molecular modeling (QM/MM) calculations for the E64c-cathepsin B complex. Our computations reveal that the hydrogen bonding network between the enzyme and the E64c (or its derivatives) determines the stereoselectivity of the subsequent ring opening reaction by governing the distance between the attacking thiolate and the attacked C2 atom of the epoxide ring. For the ( S, S)-configuration, a strong network can be realized which enables a close contact between the reacting centers, so that the irreversible step becomes very efficient. The ( R, S)-configuration ( cis-configuration) can only form networks in which the two reacting centers are so far away from each other that the irreversible step can hardly happen. The ( R, R)-configuration is in between, less optimal than the ( S, S)-configuration but much better than the ( R, S)-configuration. Exceptions where the ( R, R)-configurations shows higher potency than the ( S, S) ones are also explained.

Changing color: The pentaphenylborole–2,6‐lutidine adduct 1 has unusual photophysical properties. Cooling a solution of 1 results in the disappearance of the absorption band at 578 nm and a color change from blue to yellow. Irradiation of 1 at low temperatures leads to a migration of lutidine from boron to the adjacent carbon with BC bond formation and a color change to green.

Symmetry-adapted perturbation theory (SAPT) is used to decompose the total intermolecular interaction energy between the ammonium cation and a benzene molecule into four physically motivated individual contributions: electrostatics, exchange, dispersion, and induction. Based on this rigorous decomposition, it is shown unambiguously that both the electrostatic and the induction energy components contribute almost equally to the attractive forces stabilizing the dimer with a nonnegligible contribution coming from the dispersion term. A polarizable potential model for the interaction of ammonium cation with benzene is parametrized by fitting these four energy components separately using the functional forms of the AMOEBA force field augmented with the missing charge penetration energy term calculated as a sum over pairwise electrostatic energies between spherical atoms. It is shown that the proposed model is able to produce accurate intermolecular interaction energies as compared to ab initio results, thus avoiding error compensation to a large extent.

Fluorescence upconversion measurements of three different dendrimers G1 –G3 based on triarylamines connected by triazole linkers show a strong and fast initial decay of fluorescence anisotropy for t < 2 ps followed by anisotropy decay on a much longer time scale (10–100 ps). At the same time, a pronounced solvent relaxation takes place. Comparison of the decay data in different solvents revealed that the initial decay of fluorescence anisotropy is governed by a competition of solvent relaxation and incoherent hopping of energy between the different dendrimer branches. Thus, it is decisive to discriminate between energy transfer processes in the Franck–Condon state or in the solvent relaxed state. We demonstrate that even for charge transfer chromophores, where a large Stokes shift leads to very weak spectral overlap of donor fluorescence and acceptor absorption, rapid homotransfer is possible if there is sufficient spectral overlap with the time zero fluorescence spectrum.