A. N. Romanov

On the origin of near-IR luminescence in Bi-doped materials (II). Subvalent monocation Bi+ and cluster Bi5(3+) luminescence in AlCl3/ZnCl2/BiCl3 chloride glass

Broadband NIR photoluminescence (from 1000 to 2500 nm) was observed from partially reduced AlCl₃/ZnCl₂/BiCl₃ glass, containing subvalent bismuth species. The luminescence consists of three bands, assigned to Bi⁺ , Bi₂⁴⁺, and Bi₅³⁺ ions. The physical and optical characteristics of these centers and possible contribution to NIR luminescence from bismuth-doped oxide glasses are discussed.

New Synthetic Thrombin Inhibitors: Molecular Design and Experimental Verification

Background The development of new anticoagulants is an important goal for the improvement of thromboses treatments. Objectives The design, synthesis and experimental testing of new safe and effective small molecule direct thrombin inhibitors for intravenous administration. Methods Computer-aided molecular design of new thrombin inhibitors was performed using our original docking program SOL, which is based on the genetic algorithm of global energy minimization in the framework of a Merck Molecular Force Field. This program takes into account the effects of solvent. The designed molecules with the best scoring functions (calculated binding energies) were synthesized and their thrombin inhibitory activity evaluated experimentally in vitro using a chromogenic substrate in a buffer system and using a thrombin generation test in isolated plasma and in vivo using the newly developed model of hemodilution-induced hypercoagulation in rats. The acute toxicities of the most promising new thrombin inhibitors were evaluated in mice, and their stabilities in aqueous solutions were measured. Results New compounds that are both effective direct thrombin inhibitors (the best KI was <1 nM) and strong anticoagulants in plasma (an IC50 in the thrombin generation assay of approximately 100 nM) were discovered. These compounds contain one of the following new residues as the basic fragment: isothiuronium, 4-aminopyridinium, or 2-aminothiazolinium. LD50 values for the best new inhibitors ranged from 166.7 to >1111.1 mg/kg. A plasma-substituting solution supplemented with one of the new inhibitors prevented hypercoagulation in the rat model of hemodilution-induced hypercoagulation. Activities of the best new inhibitors in physiological saline (1 µM solutions) were stable after sterilization by autoclaving, and the inhibitors remained stable at long-term storage over more than 1.5 years at room temperature and at 4°C. Conclusions The high efficacy, stability and low acute toxicity reveal that the inhibitors that were developed may be promising for potential medical applications.

Near infrared photoluminescence of the univalent bismuth impurity center in leucite and pollucite crystal hosts

The bismuth doped aluminosilicate phases leucite (KAlSi2O6), gallium leucite (KGaSi2O6) and pollucite (CsAlSi2O6) display broadband NIR photoluminescence. The active center, responsible for this luminescence, is the Bi+ monocation, which substitutes for the large alkali metal cations. The Al,Si-disorder in the aluminosilicate framework of studied crystal phases results in the heterogeneity of Bi+ luminescent center population, which manifests itself in the characteristic dependency of the luminescence spectrum shape on the excitation wavelength. The relation of NIR emission in Bi+-doped leucite and pollucite phases to the luminescent properties of bismuth-doped glasses is also discussed.

Application of molecular modeling to urokinase inhibitors development.

Urokinase-type plasminogen activator (uPA) plays an important role in the regulation of diverse physiologic and pathologic processes. Experimental research has shown that elevated uPA expression is associated with cancer progression, metastasis, and shortened survival in patients, whereas suppression of proteolytic activity of uPA leads to evident decrease of metastasis. Therefore, uPA has been considered as a promising molecular target for development of anticancer drugs. The present study sets out to develop the new selective uPA inhibitors using computer-aided structural based drug design methods. Investigation involves the following stages: computer modeling of the protein active site, development and validation of computer molecular modeling methods: docking (SOL program), postprocessing (DISCORE program), direct generalized docking (FLM program), and the application of the quantum chemical calculations (MOPAC package), search of uPA inhibitors among molecules from databases of ready-made compounds to find new uPA inhibitors, and design of new chemical structures and their optimization and experimental examination. On the basis of known uPA inhibitors and modeling results, 18 new compounds have been designed, calculated using programs mentioned above, synthesized, and tested in vitro. Eight of them display inhibitory activity and two of them display activity about 10 μM.

Dissociative recombination of electrons and O 2 + molecular ions in the field of intense visible laser radiation

We analyze the low-temperature dissociative recombination reaction e−+O2+ → O(1D)+O(3P) in the field of visible monochromatic laser radiation. The analysis is performed in terms of the multichannel quantum defect theory using the stationary formalism of the radiative collision matrix. We calculate the dependences of the reaction cross section on the incident electron energy, the external electromagnetic field strength and frequency, and also the angle between the directions of the electron beam and the electric vector for linearly polarized radiation. The cross section is shown to increase by several orders of magnitude for a certain choice of these parameters, suggesting the possible laser stimulation of this reaction.

Dissociative recombination e− + O2+ → O(1D) + O(3P) in a strong laser field

The low-temperature dissociative recombination reaction e− + O2+ → O(1D) + O(3P) in the field of monochromatic laser radiation with the frequency range 13 000–25 000 cm−1 is studied. We take into account the direct and resonance nonradiative transitions, free–bound radiative transitions into field-induced predissociative Rydberg n1pπu(3Σ−u) states, and bound–bound dipole-allowed transitions from intermediate Rydberg states into Schumann–Runge continuum mixed with the low-lying 3pπu(3Σ−u) Rydberg state. The analysis is performed in terms of multichannel quantum defect theory (MQDT) using the stationary formalism for the radiative collision matrix. Calculations of wavefunctions and the adiabatic terms of the system are carried out. The dependences of the reaction cross section on the incident electron energy, the external electromagnetic field strength and frequency, as well as the angle between the directions of the electron beam and the electric vector for linearly polarized radiation are calculated. The cross section is shown to increase by several orders of magnitude for a certain choice of these parameters, suggesting possible laser stimulation of this reaction.

Optical properties of bismuth-doped TlCdCl3 crystal

IR photoluminescence of bismuth-doped ternary thallium chloride TlCdCl3 was studied. Two bismuth-containing luminescence impurity centers were detected. One of these was found to be the bismuth Bi+ monocation, emitting at 1025 nm.

Molecular modeling methods for supramolecular complexes: A hierarchical approach

An original hierarchical approach to the determination of the structure, stability, and properties of supramolecular complexes (SC) formed by two or more molecules (or molecular fragments of a nanoparticle) based on molecular simulation methods is proposed. The structure of the constituting SC components is calculated by quantum chemistry. It is proposed to search for possible configurations of the SC using a genetic algorithm for global optimization and a classical force field for the calculation of intermolecular interactions of the SC components. Quantum-chemical methods are used again to calculate the refined geometry, relative stability, and required properties of the SC. The free energy of formation can be determined within a quasi-harmonic approximation using molecular dynamics.

Computation of entropy contribution to protein-ligand binding free energy

The entropy contribution ΔS to protein-ligand binding free energy is studied for nine protein-lipid complexes. The entropy effect from the loss of the translational/rotational degrees of freedom (ΔStr) is calculated using the ideal gas approach. The change in the vibrational entropy (ΔSvib) is calculated using the effective quantum oscillator approach with frequencies derived from the coordinate covariance matrix, so the inharmonic effects are taken into account. The change in the entropy of solvation (ΔSsolv) is considered using the binomial cell model (developed by the authors) for the hydrophobic effect. The entropy contribution from loss of conformations that are available for the free ligand (ΔSconf) is also estimated. It is revealed that the negative in view of binding term ΔStr is only partly compensated by increasing of ΔSvib, so T(ΔStr + ΔSvib + ΔSconf) < 0 for all complexes under investigation, but taking into account ΔSsolv leads to significantly increased ΔS. For all complexes except biotin-streptavidin, the results are found to be in reasonable agreement with experimental data.

IR luminescence of bismuth-containing centers in materials prepared by impregnation and thermal treatment of porous glasses

The properties of bismuth-containing luminescent materials prepared by impregnating a porous glass with an aqueous solution of bismuth and aluminum salts followed by thermal treatment are studied. The formation of a variety of bismuth-containing centers luminescent in the near infrared range of the spectrum is revealed, one of which is the Bi+ monocation. At high temperatures, along with it, bismuth-containing cluster-type luminescent centers are apparently formed.