Protein backbone structure determination using RDC: An inverse kinematics approach with fast and exact solutions

Residual dipolar couplings (RDC) of proteins dissolved in anisotropic media promise to speed up the determination of protein structures. We consider the backbone as a robotic mechanism and formulate inverse kinematics problems using RDC restraints from two media. The φ, ψ of each secondary structure element (SSE) are computed from oriented vectors in consecutive peptide planes. We search for the optimum conformation joining the solutions of two independent backbone halves. The matrix transforming the vector Z of a global frame from one SSE into the other determines their orientation. Three distance constraints between two oriented SSE determine their relative position by solving nine polynomial equations. The benefit of this method is that complete and accurate solutions are obtained overcoming the local minima problems of heuristic procedures. The algorithm is implemented on MAPLE using the least number of experimental data; the runtimes take an order of seconds on a common PC. © 2013 Wiley Periodicals, Inc.     

Photostabilization of oxolinic acid in hydroxypropyl-β-cyclodextrins; implications for the effect of molecular self-assembly phenomena

Oxolinic acid (OXA) is a first-generation quinolone antibacterial agent, known to cause drug induced photosensitivity. In the present work its photoinduced degradation was monitored under simulated solar irradiation. The effect of photoprotecting agents on OXA stability was also assessed by drug complexation with hydroxypropyl-β-cyclodextrin (HPβCD). The complex was studied by UV-Vis and ¹H (2D) NMR Spectroscopy. A photostability indicating chromatographic method was developed and validated. Because OXA is insoluble in acidic solutions, and because an acidic solvent is necessary for successful chromatographic separation, a procedure was developed to pre-treat the sample. This method is suitable for the separation of degradation products from OXA and from each other. The method was also evaluated in the presence of HPβCD, in order to ensure that inclusion complexation did not generate inaccuracies. Investigation of OXA photodegradation profiles confirms first order kinetics and acceleration at higher initial sample concentrations. A 94% photostabilization upon complexation with HPβCD was achieved. Furthermore, molecular self association phenomena were determined by self titration experiments, using ¹H NMR Spectroscopy and suggestions were made for the photostabilization mechanism of cyclodextrins.     

Complexation of new active antibacterial adamantan derivatives with β CD: Preparation and characterization of complexes study of the thermotropic properties of pure and complex form with dipalmitoyl phosphatidylcholine bilayers

-Cyclodextrin (CD) complexes of I1-8, I1-10, I1-12, were prepared, isolated and characterized in solid and liquid form. Their thermotropic effects were studied by inserting them in DPPC bilayers both in pure and complexed forms. The results have shown that the presence of I1-8 causes spliting, broadening and lowering of the phase transition of DPPC bilayers. Their effects are more significant when I1-0 and I1-12 are inserted. These differential effects are eliminated when the above studied three molecules are incorporated in a complex form with CD in DPPC bilayers. The obtained results suggest that the bromine salts in the bilayer are likely to remain in the complex form rather than released in the membrane.     

Study of structural features and thermodynamic parameters, determining the chromatographic behaviour of drug-cyclodextrin complexes

The chromatographic behaviour of host-guest inclusion complexes was studied, in order to predict the optimal conditions for their accurate analysis and overcome the significant analytical errors generated by the presence of cyclodextrins. Complexes of tolfenamic acid and ketoprofen with beta-cyclodextrtin (betaCD), 2-hydroxypropyl-betaCD (HPbetaCD) and methyl-betaCD (MebetaCD) prepared in different molar ratios, were studied. Since the drug release from cyclodextrins' complexes is a prerequisite for its accurate quantitation, several parameters affecting the dissociation during the analysis were evaluated. In an attempt to explain the drug release mechanism from cyclodextrins, during HPLC analysis, the possible correlation of the NMR structural findings with the binding constants and the thermodynamic quantities of complexation were examined, in relation to their chromatographic behaviour. Finally, the presence of the solvation spheres around the supramolecules, which affect the complex stability, is suggested to be crucial for our chromatographic findings. Particularly, entropy change in the system is considered the most critical factor, determining the time required for dissociation of drug-cyclodextrin complexes, during drug quantitation.     

A Facile Alkylation of Aryl Aldehyde Trisylhydrazones with Trialkylboranes

Tributylborane readily alkylates aryl aldehyde trisylhydrazones to produce the corresponding alcohols in excellent yields.     

Hydrodynamic behavior of anionically prepared linear polyisoprenes and polystyrenes in carbon tetrachloride

Intrinsic viscosity, [η], weight-average molecular weight, M_w, relationships are reported for narrow molecular weight distribution linear polyisoprene and polystyrene samples in CCl₄ at 25°C. Molecular weight values cover a range nearly two orders in magnitude, extending as low as 3 × 10³. In the case of polystyrene there exists a molecular weight range (around M_w = 16,700) corresponding to a change in the Mark-Houwink-Sakurada (MHS) exponent from α = 0.71 to α = 0.54. Comparisons between the viscometric and hydrodynamic radii, from literature data, are made. For polyisoprene the MHS relationship is reported in CCl₄, for the first time. For this case α = 0.713 for the whole range of molecular weights studied. Values for the second virial coefficient from low-angle light-scattering measurements support the conclusions drawn from viscometry that CCl₄ is a good solvent for both polymers studied. The different behavior of the MHS exponent may be attributed to the difference in chain flexibility. © 1995 John Wiley & Sons, Inc.     

The effect of β-cyclodextrin on tenoxicam photostability, studied by a new liquid chromatography method; the dependence on drug dimerisation

Tenoxicam (TXM) is an effective anti-inflammatory and analgesic drug, which presents fast photochemical decomposition. In this work in an attempt to investigate the potential β-CD photostabilizing effect on TXM, the photodegradation rate of β-CD complexed drug was monitored under simulated solar irradiation from Xenon arc lamp. The photodegradation was studied at pH 7.5. A new stability indicating Liquid Chromatography method, for TXM in the presence of β-CD was used. According to the obtained results, in the case of free molecules increasing the concentration the photostability is enhanced. The effect of complexation with CDs on the photodegradation rate seems to vary depending on TXM initial concentration. At low TXM concentrations photodecomposition is retarded upon CD complexation, while at high concentrations the process is accelerated. Molecular dimerisation was studied by ¹H(1D) NMR and 2D NOESY experiments. 2D ROESY spectra of complexed molecule were evaluated in order to confirm the complexation. TXM dimers could be considered as a critical parameter affecting oxicams photostability, in combination with the already described ESIPT phenomenon.