Use Of Thermodynamic Parameters Research Articles

Lead Identification of 8-(Methylamino)-2-oxo-1,2-dihydroquinoline Derivatives as DNA Gyrase Inhibitors: Hit-to-Lead Generation Involving Thermodynamic Evaluation.

DNA gyrase and topoisomerase IV are well-validated pharmacological targets, and quinolone antibacterial drugs are marketed as their representative inhibitors. However, in recent years, resistance to these existing drugs has become a problem, and new chemical classes of antibiotics that can combat resistant strains of bacteria are strongly needed. In this study, we applied our hit-to-lead (H2L) chemistry for the identification of a new chemical class of GyrB/ParE inhibitors by efficient use of thermodynamic parameters. Investigation of the core fragments obtained by fragmentation of high-throughput screening hit compounds and subsequent expansion of the hit fragment was performed using isothermal titration calorimetry (ITC). The 8-(methylamino)-2-oxo-1,2-dihydroquinoline derivative 13e showed potent activity against Escherichia coli DNA gyrase with an IC50 value of 0.0017 μM. In this study, we demonstrated the use of ITC for primary fragment screening, followed by structural optimization to obtain lead compounds, which advanced into further optimization for creating novel antibacterial agents.

Towards elucidation of the drug release mechanism from compressed hydrophilic matrices made of cellulose ethers. III. Critical use of thermodynamic parameters of activation for modeling the water penetration and drug release processes

The two main purposes of this work were: (i) to critically consider the use of thermodynamic parameters of activation for elucidating the drug release mechanism from hydroxypropyl methylcellulose (HPMC) matrices, and (ii) to examine the effect of neutral (pH6) and acidic (pH2) media on the release mechanism. For this, caffeine was chosen as model drug and various processes were investigated for the effect of temperature and pH: caffeine diffusion in solution and HPMC gels, and drug release from and water penetration into the HPMC tablets. Generally, the kinetics of the processes was not significantly affected by pH. As for the temperature dependence, the activation energy (Ea) values calculated from caffeine diffusivities were in the range of Fickian transport (20–40kJmol−1). Regarding caffeine release from HPMC matrices, fitting the profiles using the Korsmeyer–Peppas model would indicate anomalous transport. However, the low apparent Ea values obtained were not compatible with a swelling-controlled mechanism and can be assigned to the dimensional change of the system during drug release. Unexpectedly, negative apparent Ea values were calculated for the water uptake process, which can be ascribed to the exothermic dissolution of water into the initially dry HPMC, the expansion of the matrix and the polymer dissolution. Taking these contributions into account, the true Ea would fall into the range valid for Fickian diffusion. Consequently, a relaxation-controlled release mechanism can be dismissed. The apparent anomalous drug release from HPMC matrices results from a coupled Fickian diffusion–erosion mechanism, both at pH6 and 2.

Experimental determination of adatom diffusion lengths for growth of InAs nanowires

Au-assisted InAs nanowires are grown using molecular beam epitaxy. By tailoring the growth and position of InAs nanowires, experimental values for the effective diffusion lengths of adatoms on both the substrate and nanowire sidewalls have been deduced. In the framework of a mass continuity growth model for group III elements, based on a simple kinetic but informative treatment without use of thermodynamic parameters, both shadowing effects and shared substrate diffusion areas are included. The growth model is fitted to two types of data, one for nanowires positioned in a quadratic array with varying pitch, and one for nanowires with axial heterostructures. For the given growth conditions the effective diffusion length for In adatoms on InAs NW sidewalls with wurtzite crystal structure is found to be 3μm, whereas the effective diffusion of Ga adatoms is an order of magnitude smaller. The minimum pitch to ensure independent growth, without influence from nearby NWs, is found to be around 2μm.

Surface Tension of Liquid Alloys—A Thermodynamic Approach

A formula is derived to describe the surface tensions of binary and dilute multicomponent alloys such as iron alloys. It was thermodynamically proved that the surface tension can be described by a function of the concentrations of the alloy components in bulk phase through the use of thermodynamic parameters. The formula was applied to the binary alloys, Fe-O-N and Fe-O-S systems. The described surface tensions were found to be in good agreement with the measured values.

Simulation of the Chemical Influences to the Polishing Process of Optical Glasses

In the last step of fabrication, optical and fine-optical glasses are polished to fulfill the optical requirements for their surfaces. The major influences on the process are caused by the mechanics of the polishing machine, by the chemistry (composition of the glass, as well as the polishing suspension of water and polishing grains, CeO2) [1], [2] and by the material and structure of the polishing pad. From previous own results [3], [4] it is known that the stability of the colloidal system has a major impact on the polishing results and that it is influenced by matter from the glass removal. Thus the glasses have been classified in glass families, depending on their chemical composition and their mutual compatibility in the process. As it is not always possible to measure this compatibility, the impact of the various dissolved glass ions in the fluid phase of the polishing suspension is simulated by the use of thermodynamic parameters. Therefore the specific solubility products in the aqueous phase are modeled (using, e.g., the software HSC) comprising steady accumulation of ions from the glass removal. With this simulation, the examination of the chemical part of the chemo-mechanical polishing process will be concluded.

Phase transformations and phase equilibria in Ti -25V -N system at 1200°C

The nature of phase transformations and phase equilibria in the Ti- V - N system with about 20 at.-%V and 11 -15 at.-%N has been studied at 1200°C. The results obtained for the titanium rich corner of the Ti - V- N phase diagram provide new information on phase coexistence and the composition of particular phases in this system. Thermodynamic calculations, based on the use of thermodynamic parameters from the three binary subsystems, together with newly assessed thermodynamic parameters published previously, were carried out. Reasonable agreement was obtained between the experiment and the calculations.

Spreadsheet Software for Thermodynamic Melting Point Prediction of Oligonucleotide Hybridization with and without Mismatches

The use of thermodynamic parameters for the calculation of oligonucleotide duplex stability provides the best estimates of oligonucleotide melting temperatures (Tm). Such estimates can be used for evidence-based design of molecular biological experiments in which oligonucleotide melting behavior is a critical issue, such as temperature or denaturing gradient gel electrophoreses, Southern blotting or hybridization probe assays on the LightCycler. We have developed a user friendly program for Tm calculation of matched and mismatched probes using the spreadsheet software Microsoft Excel. The most recently published values for entropy and enthalpy of Watson-Crick paris are used, and salt and oligonucleotide concentrations are considered. The 5' and 3' end stability is calculated for the estimation of primer specificity. In addition, the influence of all possible mutations under a given probe can be calculated automatically. The experimental evaluation of predicted Tm with the LightCycler, based on 14 hybridization probes for different gene loci, showed an excellent fit between measured results and values predicted with the thermodynamic model in 14 matched, 25 single mismatched and 8 two-point mismatched assays (r = 0.98; Sy. x = 0.90; y = 1.01 x -0.38). This program is extremely useful for the design of oligonucleotide probes because the use of probes that do not discriminate with a reasonable Tm difference between wild-type and mutation can be avoided in advance.

Competitive and coupled reactions

The misconception that one reaction, when coupled with another, may be driven against its free energy comes from a misunderstanding of the use of thermodynamic parameters to describe kinetic proc...

The estimation and application of surface energy data for powdered systems

AbstractEstimates of surface energies of powders can be obtained by use of contact angle data, or by use of thermodynamic parameters (e.g. calorimetric determinations). In this review, the applications of surface energy data are considered in both a pragmatic manner, which could be applied directly to the formulation and production environment, and also in a manner that could aid fundamental research into both the understanding of mechanisms by which wetting is achieved and the ways in which wetting contributes to processes such as dissolution. The approaches, which are introduced and considered, centre around spreading coefficients and compensation analysis.