Dinucleosides with Non‐Natural Backbones: A New Class of Ribonuclease A and Angiogenin Inhibitors

Ribonuclease A (RNase A) serves as a convenient model enzyme in the identification and development of inhibitors of proteins that are members of the ribonuclease superfamily. This is principally because the biological activity of these proteins, such as angiogenin, is linked to their catalytic ribonucleolytic activity. In an attempt to inhibit the biological activity of angiogenin, which involves new blood vessel formation, we employed different dinucleosides with varied non‐natural backbones. These compounds were synthesized by coupling aminonucleosides with dicarboxylic acids and amino‐ and carboxynucleosides with an amino acid. These molecules show competitive inhibition with inhibition constant (K_i) values of (59±3) and (155±5) μM for RNase A. The compounds were also found to inhibit angiogenin in a competitive fashion with corresponding K_i values in the micromolar range. The presence of an additional polar group attached to the backbone of dinucleosides was found to be responsible for the tight binding with both proteins. The specificity of different ribonucleolytic subsites were found to be altered because of the incorporation of a non‐natural backbone in between the two nucleosidic moieties. In spite of the replacement of the phosphate group by non‐natural linkers, these molecules were found to selectively interact with the ribonucleolytic site residues of angiogenin, whereas the cell binding site and nuclear translocation site residues remain unperturbed. Docked conformations of the synthesized compounds with RNase A and angiogenin suggest a binding preference for the thymine–adenine pair over the thymine–thymine pair.     

Effect of dispersion on the diffusion zone in two-phase laminar flows in microchannels

Aim of the present work is to investigate the reaction–diffusion process of a two species system under laminar flow in a T-shaped microchannel. A zone formed at the interface between the aqueous solutions of these two species is affected by advection and diffusion. Through theoretical analyses and experimental results, the effect of dispersion has been shown to influence this diffusion zone. We have defined a parameter called effective diffusivity, to account for the dispersion effects and observed it to be a function of the channel Peclet number. In the limiting case of low Peclet number, this parameter is constant and turns out to be equal to the molecular diffusivity. We have also related effective diffusivity and the dispersion coefficient through scaling estimates.     

Cobinamide chemistries for photometric cyanide determination. A merging zone liquid core waveguide cyanide analyzer using cyanoaquacobinamide

Diaquacobinamide (H₂O)₂Cbi²⁺ or its conjugate base hydroxyaquacobinamide (OH(H₂O)Cbi⁺)) can bind up to two cyanide ions, making dicyanocobinamide. This transition is accompanied by a significant change in color, previously exploited for cyanide determination. The reagent OH(H₂O)Cbi⁺ is used in excess; when trace amounts of cyanide are added, CN(H₂O)Cbi⁺ should be formed. But the spectral absorption of CN(H₂O)Cbi⁺ is virtually the same as that of OH(H₂O)Cbi⁺. It has been inexplicable how trace amounts of cyanide are sensitively measured by this reaction. It is shown here that even with excess OH(H₂O)Cbi⁺, (CN)₂Cbi is formed first due to kinetic reasons; this only slowly forms CN(H₂O)Cbi⁺. This understanding implies that CN(H₂O)Cbi⁺ will itself be a better reagent.     

Fusion around the barrier for 7Li+12C

Fusion cross-sections for the ⁷Li + ¹²C reaction have been measured at energies above the Coulomb barrier by the direct detection of evaporation residues. The heavy evaporation residues with energies below 3 MeV could not be separated out from the α-particles in the spectrum and hence their contribution was estimated using statistical model calculations. The present work indicates that suppression of fusion cross-sections due to the breakup of ⁷Li may not be significant for ⁷Li + ¹²C reaction at energies around the barrier.     

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.     

Multiporous Materials From Thermoreversible Poly(vinyledene fluoride) Gels

Poly(vinylidene fluoride)(PVF₂) produces thermoreversible gels with alkyl diesters of general formula (CH₂)_n (COOEt)₂ as well as with camphor, a naturally occurring ketone. These gels containing polymer-solvent intercalates yield multiporous materials when subjected to controlled solvent removal techniques. The micro and meso pores are attributed to polymer-solvent complexation while the macro pores are formed as a result of removal of the solvent trapped in the fibrillar network. PVF₂ –diethyl azelate (DEAZ, n = 6) and PVF₂ -camphor gels produce porous polymer network when dried by cyclohexane leaching. FESEM images exhibit porous network structures with fibrillar morphology. Mercury intrusion porosimetry (MIP) shows presence of pores having diameter in the range 4 nm–400µm for both the systems. The BJH pore size distribution curves for both systems confirm the presence of mesoporosity. The HK pore size distribution plots indicate that micropores are also created and it also puts evidence of single molecule solvent intercalation between the PVF₂ strands. The hysteresis between the extrusion and the intrusion curves indicates the presence of channel type/ink-bottle type structure in these systems.     

Torsionally broken symmetry assists infrared excitation of biomimetic charge-coupled nuclear motions in the electronic ground state

The concerted interplay between reactive nuclear and electronic motions in molecules actuates chemistry. Here, we demonstrate that out-of-plane torsional deformation and vibrational excitation of stretching motions in the electronic ground state modulate the charge-density distribution in a donor-bridge-acceptor molecule in solution. The vibrationally-induced change, visualised by transient absorption spectroscopy with a mid-infrared pump and a visible probe, is mechanistically resolved by ab initio molecular dynamics simulations. Mapping the potential energy landscape attributes the observed charge-coupled coherent nuclear motions to the population of the initial segment of a double-bond isomerization channel, also seen in biological molecules. Our results illustrate the pivotal role of pre-twisted molecular geometries in enhancing the transfer of vibrational energy to specific molecular modes, prior to thermal redistribution. This motivates the search for synthetic strategies towards achieving potentially new infrared-mediated chemistry.

Channelling vibrational excitation energy to achieve ground-state charge-transfer (CT)-assisted isomerization in a donor-bridge-acceptor molecule in solution.     

Attenuation of Sommerfeld effect in an internally damped eccentric shaft-disk system via active magnetic bearings

Meccanica - Eccentric shaft-disk system with internal damping driven by a non-ideal power source exhibits Sommerfeld effect characterized by nonlinear jump phenomena of amplitude and rotor speed...     

Investigation of the effects of silicate modification on polymer‐layered silicate nanocomposite morphology

The morphological behavior of a series of polymer‐layered silicate nanocomposites (PLSNs) has been investigated. The goal was to probe the effect of “textured” silicate surfaces on PLSN morphology. The nanocomposites were fabricated by mixing montmorillonite clay that was carefully modified with tailor‐made polystyrene (PS) surfactants into a PS homopolymer matrix, where the chemical similarity of the matrix polymer and surfactants assures complete miscibility of surfactant and homopolymer. To examine the effect of silicate surface “texture,” clay was modified with combinations of long and short surfactants. The samples were then direct melt annealed to allow the equilibrium morphology to develop, and characterized by small‐angle X‐ray scattering. Based on the implications of the Balazs model and other work on the wetting behavior of polymer melts with longer surfactants and textured surfaces we expected that the intercalation of the homopolymer matrix material into the modified clay would be promoted. Extensive characterization of both the modified clays as well as the resultant nanocomposites clearly show that the modified clays exhibit a high degree of order, but also that only phase‐separated morphologies are formed in the corresponding nanocomposites. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 4075–4083, 2004