The dynamics of protein conformational changes, from protein folding to smaller changes, such as those involved in ligand binding, are governed by the properties of the conformational energy landscape. Different techniques have been used to follow the motion of a protein over this landscape and thus quantify its properties. However, these techniques often are limited to short timescales and low-energy conformations. Here, we describe a general approach that overcomes these limitations. Starting from a nonnative conformation held by an aromatic disulfide bond, we use time-resolved spectroscopy to observe nonequilibrium backbone dynamics over nine orders of magnitude in time, from picoseconds to milliseconds, after photolysis of the disulfide bond. We find that the reencounter probability of residues that initially are in close contact decreases with time following an unusual power law that persists over the full time range and is independent of the primary sequence. Model simulations show that this power law arises from subdiffusional motion, indicating a wide distribution of trapping times in local minima of the energy landscape, and enable us to quantify the roughness of the energy landscape (4-5 k B T). Surprisingly, even under denaturing conditions, the energy landscape remains highly rugged with deep traps (>20 k B T) that result from multiple nonnative interactions and are sufficient for trapping on the millisecond timescale. Finally, we suggest that the subdiffusional motion of the protein backbone found here may promote rapid folding of proteins with low contact order by enhancing contact formation between nearby residues. photochemical trigger | subdiffusion M ajor advances have been made in recent years in understanding dynamic aspects of protein conformational changes, particularly protein folding; however, many issues remain to be solved (1). Among these are the properties of the unfolded protein ensemble and the role of residual structure of denatured proteins in promoting folding (2), the heterogeneity of microscopic folding pathways (3), and the existence of multiple distinct, but only transiently populated, intermediates (4). Particularly for fast-folding proteins, the idea of downhill folding, i.e., the absence of a significant barrier, has been suggested as an alternative mechanism (5, 6), but it is not clear to what extent fast-folding proteins make use of this mechanism. On the other hand, technical progress has made it possible to observe multiple folding and unfolding events in millisecond all-atom molecular dynamics simulations. Such simulations have shown that some proteins always follow the same folding pathway, whereas others have several different pathways (7). Moreover, individual folding events occur with submicrosecond transit times through a distinct transition state but are separated by long waiting times, which yield the experimentally observed folding times (8).The idea of motion on a rugged energy landscape (9-11) has been used widely to describe conformational changes in protei...

Fluconazole is known as an antifungal drug since 1983. Its propensity for the formation of new polymorphs and salts has been reported in the literature, mostly by powder X-ray diffraction and solid state Raman spectroscopy. In the present study, we are elucidating the structures of four polymorphs of fluconazole using single crystal X-ray diffraction. Raman spectra of the single crystals of these polymorphs also support our study. These polymorphs were grown in the presence of the cocrystal formers. This indicates that fluconazole interacts with the cocrystal former in the solution, and possibly these interactions result into the generation of new polymorphs of it. These polymorphs of fluconazole exhibit the conformational flexibility of the molecule, and hence we observed seven different conformers of the molecule in the reported polymorphs. Although these forms have strong O–H···N hydrogen bonds, the nature of the packing of the molecules is a cumulative effect of a number of weaker intermolecular forces such as C–H···O, C–H···N, and C–H···F and the strong hydrogen bond.

No abstract

A library of halogen-substituted azobenzenes (ABs) have been synthesized and structurally characterized by single crystal Xray diffraction technique. Azobenzenes studied herein display fast photo switching properties. Kinetics of cis-! transisomerization has been studied using UV-VIS spectroscopy and the rate constant for this transformation were determined. Optimization of probable conformers of the cis-isomer and the corresponding transition state (TS) were carried out to determine the energy of activation. The Time-Dependent Density Functional Theory (TD-DFT) calculations were also performed to gain insight into the photo-isomerization. Our results indicate that the fluorinated compounds display better kinetic stability of the cis-isomer compared to the corresponding chloro and bromo analogues.

Considering the fundamental and most desirable characteristics of energetic materials, a series of 1,2,3-triazole-based heterocyclic energetic motifs nicely tuned with nitrato (−ONO 2 ) functionality were synthesized by a microwave-assisted environmental friendly synthetic approach with good yields. Thermal stability and the nature of evolved gases on decomposition of structurally characterized energetic motifs were analyzed by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) analysis and Fourier transform infrared coupled with TGA–DSC. The explosiveness of these motifs was explored by calculation of enthalpy of formation and density employing density functional theory, and the detonation performances (detonation pressure and velocity) were explored using EXPLO5_V6.03. All of these compounds were calculated to have better oxygen balance (−36 to −52%) as compared to that of trinitrotoluene (−74%). Most of the nitrate ester derivatives were found to exhibit low impact sensitivities, high densities, good thermal stabilities, and promising detonation properties, and PN 3 was observed to be a superior candidate in terms of its energetic characteristics. Hence, the experimental and theoretical outcomes strongly reflect that the present approach of developing dendritic high energetic materials bearing green explosive characteristics might be a potential pathway for designing and synthesizing green explosives with desired characteristics.