Cu(I)‐Catalyzed Efficient Synthesis of 2′‐Triazolo‐nucleoside Conjugates

A small library of thirty‐two 2′‐triazolyl uridine and 2′‐triazolyl‐5‐methyluridine has been synthesized by Cu(I)‐catalyzed condensation of 2′‐azido‐2′‐deoxyuridine and 2′‐azido‐2′‐deoxy‐5‐methyluridine with different alkynes and aryl propargyl ethers in almost quantitative yields. Triazolo‐nucleoside conjugates, which can be evaluated for different biological activity for suitable drug development, were unambiguously identified on the basis of ¹H NMR, ¹³C NMR, IR, and HRMS data analysis. These compounds have been synthesized for the first time and have not been reported in the literature earlier.     

A class of hypo-elastic non-elastic materials and their thermodynamics

Thermodynamics is developed for a class of thermo-hypo-elastic materials. It is shown that materials of this class obey the laws of thermodynamics, but are not elastic.

Table of Symbols

Latin Letters A _ijkl tensor-valued function of t _ij appearing in hypo-elastic constitutive relation - B _ijkl another tensor-valued function. See equation (4.2) - B the square of - d _ij rate of deformation tensor - d _ij deviator of rate of deformation - f, k functions of pressure, p - g, h functions of the invariant - p pressure - q _i heat flux vector - s _ij stress deviator - _ij co-rotational derivative of stress deviator - t time - t ₁ t ₂ specific values of time - t _ij stress tensor - t _ij ⁰ a specific value of stress - T Temperature - T ₀ a specific value of temperature - u _i velocity - V(t) a material volume as a function of time, t - V ₀ a material volume at a reference configuration - W work (W = work done in a deformation—section 5) Sript Letters Specific internal energy - Specific Helmholtz free energy - G Specific Gibbs function Greek Letters an invariant of the stress deviator—see eq. (2.4) - _ij kroneker delta - (W = work done in a deformation—section 5) - specific entropy - hypo-elastic potential - hypo-elastic potential - mass density - ₀ mass density in a reference configuration - specific volume = 1/ - a function of p - _ijkl a constant tensor—see eq. (2.5) - –G/ - _ij rate of rotation tensor This work is dedicated to Jerald L. Ericksen, without whose influence it would not have been possible     

Computational protocols for prediction of solute NMR relative chemical shifts. a case study of L-tryptophan in aqueous solution

In this study, we have applied two different spanning protocols for obtaining the molecular conformations of L-tryptophan in aqueous solution, namely a molecular dynamics simulation and a molecular mechanics conformational search with subsequent geometry re-optimization of the stable conformers using a quantum mechanically based method. These spanning protocols represent standard ways of obtaining a set of conformations on which NMR calculations may be performed. The results stemming from the solute-solvent configurations extracted from the MD simulation at 300 K are found to be inferior to the results stemming from the conformations extracted from the MM conformational search in terms of replicating an experimental reference as well as in achieving the correct sequence of the NMR relative chemical shifts of L-tryptophan in aqueous solution. We find this to be due to missing conformations visited during the molecular dynamics run as well as inaccuracies in geometrical parameters generated from the classical molecular dynamics simulations.     

Use of engineered unique cysteine residues to facilitate oriented coupling of proteins directly to a gold substrate

A prerequisite for any "lab on a chip" device that utilizes an electrical signal from the sensor protein is the ability to attach the protein in a specific orientation onto a conducting substrate. Here, we demonstrate the covalent attachment to a gold surface of light-harvesting membrane proteins, from Rhodobacter sphaeroides, via cysteine (Cys) residues engineered on either the cytoplasmic or periplasmic face. This simple directed attachment is superior in its ability to retain light-harvesting complex (LHC) function, when compared to a similar attachment procedure utilizing a self-assembled monolayer on gold. LH 1 has previously been observed to have superior photostability over LH 2 (Magis et al. [2010] Biochim. Biophys. Acta, 1798, 637-645); this characteristic is maintained even with the introduction of Cys residues.     

In vitro evolution of ligands to the membrane protein caveolin

Membrane proteins comprise a third of the human genome, yet present challenging targets for reverse chemical genetics. For example, although implicated in numerous diseases including multiple myeloma, the membrane protein caveolin-1 appears to offer a poor target for the discovery of synthetic ligands due to its largely unknown structure and insolubility. To break this impasse and identify new classes of caveolae controlling lead compounds, we applied phage-based, reverse chemical genetics for the discovery of caveolin-1 ligands derived from the anti-HIV therapeutic T20. Substitution of homologous residues into the T20 sequence used a process analogous to medicinal chemistry for the affinity maturation to bind caveolin. The resultant caveolin-1 ligands bound with >1000-fold higher affinity than wild-type T20. Two types of ELISAs and isothermal titration calorimetry (ITC) measurements demonstrated high affinity binding to caveolin by the T20 variants with K(d) values in the 150 nM range. Microscopy experiments with the highest affinity caveolin ligands confirmed colocalization of the ligands with endogenous caveolin in NIH 3T3 cells. The results establish the foundation for targeting caveolin and caveolae formation in living cells.     

Development of an HPLC method for determination of pentachloronitrobenzene, hexachlorobenzene and their possible metabolites

Background

Pentachloronitrobenzene (PCNB) and hexachlorobenzene (HCB) are highly toxic and widespread in every environmental compartment. Some of metabolic products such as amino/nitro containing chlorinated aromatic compounds can be determined by gas chromatography coupled with electron capture detector (GC-ECD). However, it is difficult to identify some of chlorophenolic and chloroquinolic intermediates produced from PCNB and HCB by the above mentioned technique. Therefore, for analysis of these compounds and their metabolites, we have developed a high performance liquid chromatography (HPLC) based method.

Results

The extraction of PCNB and HCB from soil and minimal salt medium was carried out with ethyl acetate and hexane respectively with good recoveries (98% for PCNB and 97% for HCB). The validation of the proposed extraction and HPLC method was done by analysis of PCNB and HCB biodegradation and their metabolites identification from anaerobic enriched soil samples.

Conclusion

A rapid, sensitive and simple HPLC based analytical method was developed for the analysis of PCNB, HCB and their possible intermediates.     

A neutral redox-switchable [2]rotaxane

A limited range of redox-active, rotaxane-based, molecular switches exist, despite numerous potential applications for them as components of nanoscale devices. We have designed and synthesised a neutral, redox-active [2]rotaxane, which incorporates an electron-deficient pyromellitic diimide (PmI)-containing ring encircling two electron-rich recognition sites in the form of dioxynaphthalene (DNP) and tetrathiafulvalene (TTF) units positioned along the rod section of its dumbbell component. Molecular modeling using MacroModel guided the design of the mechanically interlocked molecular switch. The binding affinities in CH(2)Cl(2) at 298 K between the free ring and two electron-rich guests--one (K(a) = 5.8 × 10(2) M(-1)) containing a DNP unit and the other (K(a) = 6.3 × 10(3) M(-1)) containing a TTF unit--are strong: the one order of magnitude difference in their affinities favouring the TTF unit suggested to us the feasibility of integrating these three building blocks into a bistable [2]rotaxane switch. The [2]rotaxane was obtained in 34% yield by relying on neutral donor-acceptor templation and a double copper-catalysed azide-alkyne cycloaddition (CuAAC). Cyclic voltammetry (CV) and spectroelectrochemistry (SEC) were employed to stimulate and observe switching by this neutral bistable rotaxane in solution at 298 K, while (1)H NMR spectroscopy was enlisted to investigate switching upon chemical oxidation. The neutral [2]rotaxane is a chemically robust and functional switch with potential for applications in device settings.     

Random self-affine multifractal Sierpinski sponges in $${\mathbb{R}^d}$$

In this paper we study the Hausdorff and packing dimensions and the Rényi dimensions of random self-affine multifractal Sierpinski sponges in \({\mathbb{R}^{d}}\).     

Six-dimensional quasiclassical and quantum dynamics of H2 dissociation on the c(2 × 2)-Ti/Al(100) surface

Based on a slab model of H(2) dissociation on a c(2 × 2) structure with Ti atoms in the first and third layers of Al(100), a six-dimensional (6D) potential energy surface (PES) has been built. In this PES, a molecular adsorption well with a depth of 0.45 eV is present in front of a barrier of height 0.13 eV. Using this PES, H(2) dissociation probabilities are calculated by the classical trajectory (CT), the quasiclassical trajectory (QCT), and the time-dependent wave-packet (TDWP) method. The QCT study shows that trajectories can be trapped by the molecular adsorption well. Higher incident energy can lead to direct H(2) dissociation. Vibrational pre-excitation is the most efficient way to promote direct dissociation without trapping. We find that both rotational and vibrational excitation have efficacies close to 1.0 in the entire range of incident energies investigated, which supports the randomization in the initial conditions making the reaction rate solely dependent on the total (internal and translational) energy. The H(2) dissociation probabilities from quantum dynamics are in reasonable agreement with the QCT results in the energy range 50-200 meV, except for some fluctuations. However, the TDWP results considerably exceed the QCT results in the energy range 200-850 meV. The CT reaction probabilities are too low compared with the quantum dynamical results.     

Two- and four-component relativistic generalized-active-space coupled cluster method: implementation and application to BiH

A string-based coupled-cluster method of general excitation rank and with optimal scaling which accounts for special relativity within the four-component framework is presented. The method opens the way for the treatment of multi-reference problems through an active-space inspired single-reference based state-selective expansion of the model space. The evaluation of the coupled-cluster vector function is implemented by considering contractions of elementary second-quantized operators without setting up the amplitude equations explicitly. The capabilities of the new method are demonstrated in application to the electronic ground state of the bismuth monohydride molecule. In these calculations simulated multi-reference expansions with both doubles and triples excitations into the external space as well as the regular coupled-cluster hierarchy up to full quadruples excitations are compared. The importance of atomic outer core-correlation for obtaining accurate results is shown. Comparison to the non-relativistic framework is performed throughout to illustrate the additional work of the transition to the four-component relativistic framework both in implementation and application. Furthermore, an evaluation of the highest order scaling for general-order expansions is presented.