Synthesis of New 1,3‐Benzoxazines from Ketimines and Their Bioevaluation

A new series of 1,3‐Benzoxazines were synthesized from ketimines and triphosgene. The synthesized compounds were characterized by IR, ¹HNMR, and mass spectral data. The synthesized compounds on bioevaluation indicated significant antifungal activity.     

Biocatalytic Synthesis of Allylic and Allenyl Sulfides through a Myoglobin‐Catalyzed Doyle–Kirmse Reaction

The first example of a biocatalytic [2,3]‐sigmatropic rearrangement reaction involving allylic sulfides and diazo reagents (Doyle–Kirmse reaction) is reported. Engineered variants of sperm whale myoglobin catalyze this synthetically valuable C?C bond‐forming transformation with high efficiency and product conversions across a variety of sulfide substrates (e.g., aryl‐, benzyl‐, and alkyl‐substituted allylic sulfides) and α‐diazo esters. Moreover, the scope of this myoglobin‐mediated transformation could be extended to the conversion of propargylic sulfides to give substituted allenes. Active‐site mutations proved effective in enhancing the catalytic efficiency of the hemoprotein in these reactions as well as modulating the enantioselectivity, resulting in the identification of the myoglobin variant Mb(L29S,H64V,V68F), which is capable of mediating asymmetric Doyle–Kirmse reactions with an enantiomeric excess up to 71 %. This work extends the toolbox of currently available biocatalytic strategies for the asymmetric formation of carbon–carbon bonds.     

Photoinduced electron transfer in a hexaphenylbenzene-based self-assembled porphyrin-fullerene triad

A hexaphenylbenzene-based zinc porphyrin dyad forms a 1:1 complex with a fullerene bearing two pyridyl groups via coordination of the pyridyl nitrogens with the zinc atoms. The fullerene is symmetrically located between the two zinc porphyrins. The binding constant for the complex is 7.3 x 10(4) M(-1) in 1,2-difluorobenzene. Photoinduced electron transfer from a porphyrin first excited singlet state to the fullerene occurs with a time constant of 3 ps, and the resulting charge-separated state has a lifetime of 230 ps. This self-assembled construct should form a basis for the construction of more elaborate model photosynthetic antenna-reaction center systems.     

Polar networks control oligomeric assembly in membranes

Polar interactions have a profound influence on membrane stability and structure. A membrane-solubilized GCN4 peptide, MS-1, is used to study the impact of polar networks. Amide functionalities from amino acid side chains have been shown to promote peptide oligomerization, but lacked specificity. Herein, the hydrogen bonding interactions of an Asn side chain are coupled with the hydroxyl of Ser or Thr to generate a polar network. Analytical ultracentrifugation and fluorescence resonance energy transfer studies indicate that a trimer assembly is established where each membrane-embedded hydrogen bond contributes 1 kcal mol-1.     

Computational design of heterochiral peptides against a helical target

Polypeptides incorporating D-amino acids occasionally occur in nature and are an important class of pharmaceutical molecules. With the use of heterochiral Monte Carlo (HCMC), a method inspired by the de novo design of proteins, we develop peptide scaffolds for interacting with a molecular target, a left-handed alpha-helix. The HCMC approach concurrently seeks to optimize a peptide sequence, its internal conformation, and its docked conformation with a target surface. Several major classes of interactions are observed: (1) homochiral interactions between two alphaL helices, (2) heterochiral interactions between an alphaL and an alphaR helix, and (3) heterochiral interactions between the alphaL target and novel nonhelical structures. We explore the application of HCMC to simulating the preferential enantioselectivity of heterochiral complexes. Implications for biomimetic design in molecular recognition are discussed.     

Assessment of Dentifrices Against Candida Biofilm

The invasion of opportunistic pleiomorphic Candida albicans into oral cavity environment leads to development and progression of its resistance to both naturally occurring antifungal peptides in human saliva as well as commercially available antifungal therapies. As a result of this, the usage and popularity of natural medicine and dentifrices had increased significantly in the last decade. In the present investigation, we have assessed the action of locally available dentifrices against C. albicans biofilm. Disk diffusion test showed maximum zone of inhibition (20?mm) by herbal dentifrice (D-5) as compared to other dentifrices when incubated at 37?°C and 48?h. Assessment of dentifrice D-5 for its effectiveness against C. albicans was further shown in MIC₉₀ (3.12?mg?mL^?1) and SMIC₉₀ (6.2?mg?mL^?1) values for planktonic and sessile cells (biofilm forming), respectively. Our data depicted 80% reduction in the cell surface hydrophobicity when 6.2?mg?mL^?1 of herbal dentifrice D-5 was used against 48-h grown Candida biofilm at 37?°C. Visualization of herbal dentifrice D-5-treated C. albicans biofilm under SEM revealed drastic reduction in the dense network of yeast, hyphae, and pseudohyphae enclosed in its ECM as compared to its control biofilm. The data were further supported by CLSM analysis which depicted C. albicans architecture disruption by herbal dentifrices. From the above data, it is inferred that these studies would provide researchers and medical practitioners with better insight into the antifungal effect of natural herbal dentifrices.     

Computational study on energetic properties of nitro derivatives of furan substituted azoles

Density functional theory has been used to investigate geometries, heats of formation (HOFs), C-NO₂ bond dissociation energies (BDEs), and relative energetic properties of nitro derivatives of azole substituted furan. HOFs for a series of molecules were calculated by using density functional theory (DFT) and Møller–Plesset (MP2) methods. The density is predicted using crystal packing calculations; all the designed compounds show density above 1.71 g/cm³. The calculated detonation velocities and detonation pressures indicate that the nitro group is very helpful for enhancing the detonation performance for the designed compounds. Thermal stabilities have been evaluated from the bond dissociation energies. Charge on the nitro group was used to assess the impact sensitivity in this study. According to the results of the calculations, tri- and tetra-nitro substituted derivatives reveal high performance with better thermal stability.     

High-speed frictional slip at metal-on-metal interfaces

In this study plate-impact pressure-shear friction experiments are employed to investigate dynamic slip resistance and time-resolved growth of molten metal films during dry metal-on-metal slip under extreme interfacial conditions. By employing a tribo-pair comprising of a hard tool-steel against a relatively low melt-point metal (7075-T6 Al alloy), interfacial normal stress of up to 5 GPa and slip speeds of approximately 250 m/s have been achieved. These extreme interfacial conditions are conducive to the development of molten metal film at the tribo-pair interface. A Lagrangian finite element code is developed to understand the evolution of the thermo-mechanical fields and their relationship to the observed slip response. The code accounts for dynamic effects, heat conduction, contact with friction, and full thermo-mechanical coupling. At temperatures below the melting point of the tribo-pair materials are described as isotropic, thermally softening, elastic–viscoplastic solids. For material elements with temperatures in excess of the melt temperature a purely Newtonian fluid constitutive model is employed.     

Extension of Lagrangian–Hamiltonian mechanics for continuous systems—investigation of dynamics of a one-dimensional internally damped rotor driven through a dissipative coupling

In this paper, the extended Lagrangian formulation for a one-dimensional continuous system with gyroscopic coupling and non-conservative fields has been developed. Using this formulation, the dynamics of an internally and externally damped rotor driven through a dissipative coupling has been studied. The invariance of the extended or so-called umbra-Lagrangian density is obtained through an extension of Noether’s theorem. The rotor shaft is modeled as a Rayleigh beam. The dynamic behavior of the rotor shaft is obtained and validated through simulation studies. Results show an interesting phenomenon of limiting behavior of the rotor shaft with internal damping beyond certain threshold speeds which are obtained theoretically and affirmed by simulations. It is further observed that there is entrainment of whirling speeds at natural frequencies of the rotor shaft primarily depending on the damping ratio.     

Use of a modified torsional Kolsky bar to study frictional slip resistance in rock-analog materials at coseismic slip rates

The knowledge of shear resistance in earth faults is of fundamental importance to our understanding of the magnitude of stress drop and the associated energy release during typical seismic rupture events. In the present study a modified torsional Kolsky bar is employed to investigate frictional slip resistance in rock-analog materials (i.e., quartz and soda lime glass) at normal stresses of relevance to earthquake physics (30–80 MPa) and co-seismic slip rates. The results indicate the coefficient of kinetic friction to be in the range of 0.2 to 0.3. These values of the coefficient of friction are much lower when compared to those obtained in rocks at quasi-static slip rates. In all experiments slip weakening is observed and is preceded by slip strengthening. The slip weakening is understood to be due to thermal weakening induced by flash-heating at asperity contacts and requires a few mm of slip to be effective; the slip strengthening is understood to be due to an increase in the real area of contact at the asperity junctions due to localized plastic flow and subsequent coalescence and solidification of local softened/melt patches at the slip interface.