Use of thermo‐Raman spectroscopy and chemometric analysis to identify dehydration steps of hydrated inorganic samples—application to copper sulfate pentahydrate

In situ thermo‐Raman spectroscopy (TRS) measurements were performed in order to investigate solid‐phase transformation of the copper sulfate pentahydrate from room temperature up to 300 °C. Band‐target entropy minimization (BTEM), a blind‐source separation algorithm, was employed in order to identify and reconstruct the pure component spectra of the species involved in the dehydration process. In spite of low signal‐to‐noise ratio and elevated baseline spectral data, BTEM was successfully utilized to identify and reconstruct four pure component spectra of copper sulfate pentahydrate, trihydrate, monohydrate, and anhydrate, which were formed during this thermally induced process. Subsequent mapping of these four pure component spectral estimates back onto the preprocessed spectra yielded the relative concentrations of each individual species. Finally, the transition temperatures of each dehydration step could be unambiguously deduced from the obtained concentration profile. The current study shows that combined thermo‐Raman spectroscopy and chemometric analysis provides an effective tool to determine the dehydration temperatures as well as to identify the structures of each individual species involved in a solid‐phase dehydration process. Copyright © 2009 John Wiley & Sons, Ltd.     

Cyclin-Dependent Kinase 4 and 6 Inhibitors in Cell Cycle Dysregulation for Breast Cancer Treatment

In cell development, the cell cycle is crucial, and the cycle progression’s main controllers are endogenous CDK inhibitors, cyclin-dependent kinases (CDKs), and cyclins. In response to the mitogenic signal, cyclin D is produced and retinoblastoma protein (Rb) is phosphorylated due to activated CDK4/CDK6. This causes various proteins required in the cell cycle progression to be generated. In addition, complexes of CDK1-cyclin A/B, CDK2-cyclin E/A, and CDK4/CDK6-cyclin D are required in each phase of this progression. Cell cycle dysregulation has the ability to lead to cancer. Based on its role in the cell cycle, CDK has become a natural target of anticancer therapy. Therefore, understanding the CDK structures and the complex formed with the drug, helps to foster the development of CDK inhibitors. This development starts from non-selective CDK inhibitors to selective CDK4/CDK6 inhibitors, and these have been applied in clinical cancer treatment. However, these inhibitors currently require further development for various hematologic malignancies and solid tumors, based on the results demonstrated. In drug development, the main strategy is primarily to prevent and asphyxiate drug resistance, thus a determination of specific biomarkers is required to increase the therapy’s effectiveness as well as patient selection suitability in order to avoid therapy failure. This review is expected to serve as a reference for early and advanced-stage researchers in designing new molecules or repurposing existing molecules as CDK4/CDK6 inhibitors to treat breast cancer.     

Experimental dipole moments for nonisolatable acetic acid structures in a nonpolar medium. A combined spectroscopic, dielectric, and DFT study for self-association in solution

Acetic acid can exist in many possible structural forms depending on its surrounding medium. A recently developed inverse problem methodology (J. Phys. Chem. B 2007, 111, 13064-13074) was utilized in order to elucidate acetic acid structures in a dilute nonpolar medium. In this regard, simultaneous and stopped-flow measurements of the bulk solution densities, refractive indices, relative permittivities, and IR spectra of acetic acid in toluene were performed at several different concentrations in a semibatch closed-loop experimental setup at 298.15 K and 0.1013 MPa. This combined IR spectroscopic and dielectric, density, and refractive index analysis was employed in order to distinguish acetic acid structures and to further determine the dipole moments of the monomer, cyclic dimer, and "lumped-sum" open dimers. The infrared spectra were first analyzed to provide qualitative understanding as well as quantitative estimates for each acetic acid species. Subsequently, the dipole moments of these species were calculated using a direct approach which was primarily based on response surface models. The present method allows the determination of individual dipole moments not only for the monomer but also for the cyclic dimer and the open dimer. The results obtained from this study experimentally show that the cyclic dimer with centrosymmetric structure has a dipole moment approximately 0 D. The results also suggest that the linear dimers are present as mixtures of linear dimers structures. The existence of the linear dimers mixture was also indicated by the experimental infrared analysis of the OH-stretching region (particularly for measurements in n-hexane as solvent) and comparison of these spectra with DFT predictions. Finally, the present methodology which incorporates simultaneous physicochemical and spectroscopic analysis is undoubtedly useful for physicochemical characterization for other nonisolatable solute species and self-associated structures in solution.     

Resonance-enhanced multiphoton ionisation photoelectron spectroscopy of the ClO radical: the C 2 sigma- state

A (2 + 1) one-colour resonance-enhanced multiphoton ionisation study is carried out on the C 2 sigma- state of the ClO radical in the one-photon energy range 29,500-31,250 cm-1. The ClO radical is produced by one-photon photolysis of ClO2 employing 359.2 nm photons derived from a separate laser. In this way a significant concentration of vibrationally excited ClO in its spin-orbit split X 2 pi omega (omega = 3/2 or 1/2) electronic ground state is produced. In addition to mass-resolved excitation spectra, kinetic-energy resolved photoelectron spectra for the X 3 sigma-(v+)<--C 2 sigma-(v' = 3-5) transitions are measured. These transitions are not completely Frank-Condon diagonal, and indicate a decrease in bond length on removal of the Rydberg electron from the C 2 sigma- state. In addition to an unambiguous assignment of the C 2 sigma- state, valuable information is obtained on the degree of vibrational excitation with which the nascent ClO radical is formed in the photolysis of ClO2. Analysis of the photoelectron spectra is supported by Franck-Condon calculations based on potential energy curves either from experimental spectroscopic parameters, or obtained by theoretical ab initio methods.     

Combined Online Spectroscopic,Calorimetric, and Chemometric Analysis: Reaction Enthalpy Determinations in Single and Parallel Reactions

Calorimetry and signal processing : Vibrational spectroscopies, heat‐flow microcalorimetry, and multivariate analysis are combined to decouple the reaction enthalpies of parallel reactions (see picture). This methodology allows the evaluation of reaction enthalpy from complex systems without recourse to conventional kinetic modeling.

     

The direct determination of partial molar volumes and reaction volumes in ultra-dilute non-reactive and reactive multi-component systems using a combined spectroscopic and modified response surface model approach

Two experimental multi-component organometallic systems were studied, namely, (1) a non-reactive system consisting of [Mo(CO)(6)], [Mn(2)(CO)(10)], and [Re(2)(CO)(10)] in toluene under argon at 298.15 K and 0.1 MPa and (2) a reactive system consisting of [Rh(4)(CO)(12)] + PPh(3)--> [Rh(4)(CO)(11)PPh(3)] + CO in n-hexane under argon at 298.15 K and 0.1 MPa. The mole fractions of all solutes were less than 140 x 10(-6) in system (1) and less than 65 x 10(-6) in system (2). Simultaneous in-situ FTIR spectroscopic measurements and on-line oscillatory U-tube density measurements were performed on the multi-component solutions. A newly developed response surface methodology was applied to the data sets to determine the individual limiting partial molar volumes of all constituents present as well as the reaction volume. The limiting partial molar volumes obtained for system (1) were 176.4 +/- 2.5, 265.1 +/- 2.4, and 276.8 +/- 2.4 cm(3) mol(-1) for [Mo(CO)(6)], [Mn(2)(CO)(10)], and [Re(2)(CO)(10)], respectively and are consistent with independent binary experiments. The limiting partial molar volumes obtained for system (2) were 310.7 +/- 2.7, 219.8 +/- 2.2 and 461.5 +/- 4.5 cm(3) mol(-1) for [Rh(4)(CO)(12)], PPh(3) and [Rh(4)(CO)(11)PPh(3)], respectively. In addition, a reaction volume Delta(r)V equal to -17.0 +/- 5.7 cm(3) mol(-1) was obtained. The present results demonstrate that both partial molar volumes and reaction volumes can be obtained directly from multi-component organometallic solutions. This development provides a new tool for physico-chemical determinations relevant to a variety of solutes and their reactions.     

Photoelastic determination of stresses in multiple-pin connectors

The design, fabrication, and testing of photoelastic models of double-lap, multiple-pin connectors are discussed. Interest is in the stresses in the inner laps. These stresses are determined by constructing models with photoelastic inner laps and transparent-acrylic outer laps. The connectors have two pins, in tandem, parallel to the load direction. A photoelastic-isotropic point is shown to permit the evaluation of load sharing between the two pins. A numerical scheme, utilizing the isochromatic- and isoclinic-photoelastic data and a finite-difference representation of the planestress equilibrium equations, is used to compute the stresses around the two pins. Representative stress distributions and stress-concentration factors are shown.     

Phage display-derived inhibitor of the essential cell wall biosynthesis enzyme MurF

Background  

To develop antibacterial agents having novel modes of action against bacterial cell wall biosynthesis, we targeted the essential MurF enzyme of the antibiotic resistant pathogen Pseudomonas aeruginosa. MurF catalyzes the formation of a peptide bond between D-Alanyl-D-Alanine (D-Ala-D-Ala) and the cell wall precursor uridine 5'-diphosphoryl N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid (UDP-MurNAc-Ala-Glu-meso-A2pm) with the concomitant hydrolysis of ATP to ADP and inorganic phosphate, yielding UDP-N-acetylmuramyl-pentapeptide. As MurF acts on a dipeptide, we exploited a phage display approach to identify peptide ligands having high binding affinities for the enzyme.     

Deuterium isotope effect on molar heat capacities and apparent molar heat capacities in dilute aqueous solutions: A multi-channel heat-flow microcalorimeter study

The molar heat capacities of chloroform, dichloromethane, methanol, acetonitrile, acetone, dimethyl sulfoxide, benzene, dimethylformamide, toluene, and cyclohexane, as well as their deuterated isotopologues, were measured using a multi-channel heat conduction TAM (Thermal Activity Monitor) III microcalorimeter. In addition, the apparent molar heat capacities of some of the associated dilute aqueous solutions (0.0039 < solute mole fraction, x_i < 0.0210) were also measured. A temperature drop method from (298.15 to 297.15) K at 0.1 MPa was employed. The corresponding heat capacities were determined from the integration of the measured heat flow. The heat capacity results are shown to be in good to very good agreement with the available literature values. In addition, good correlations were obtained for the effect of isotopic substitution on both molar heat capacity and apparent molar heat capacity in aqueous solutions. These correlations should be useful in the prediction of the molar heat capacities or the apparent molar heat capacities of other deuterated compounds. Since these measurements were conducted with ampoules, the effects of heat of condensation and/or vapor space on the accuracy of the heat capacity determinations are discussed. The overall results from this study demonstrate the utility of a multi-channel heat conduction microcalorimeter in obtaining good reproducibility and good accuracy for molar heat capacities as well as apparent molar heat capacities from simultaneous samples.