Purity determination of a new antifungal drug candidate using quantitative 1H NMR spectroscopy: Method validation and comparison of calibration approaches

Quantitative nuclear magnetic resonance (qNMR) is an analytical technique that offers numerous advantages in pharmaceutical applications including minimum sample preparation and rapid data collection times with no need for response factor corrections, being a powerful tool for assaying drug content in both drug discovery and early drug development. In the present work, we have applied qNMR, using both the internal standard and the electronic reference to access in vivo concentrations 2 calibration methods, to assess the purity of RI76, a novel antifungal drug candidate. NMR acquisition and processing parameters were optimized in order to obtain spectra with intense, well-resolved signals of completely relaxed nuclei. The analytical method was validated following current guidelines, demonstrating selectivity, linearity, accuracy, precision, and robustness. The calibration approaches were statistically compared, and no significant difference was observed when comparing the obtained results and their dispersion in terms of relative standard deviation. The proposed qNMR method may, therefore, be used for both qualitative and quantitative assessments of RI76 in early drug development and for characterization of this compound.     

Triesterase and Promiscuous Diesterase Activities of a Di‐CoII‐Containing Organophosphate Degrading Enzyme Reaction Mechanisms

The reaction mechanism for the hydrolysis of trimethyl phosphate and of the obtained phosphodiester by the di‐Co^II derivative of organophosphate degrading enzyme from Agrobacterium radiobacter P230(OpdA), have been investigated at density functional level of theory in the framework of the cluster model approach. Both mechanisms proceed by a multistep sequence and each catalytic cycle begins with the nucleophilic attack by a metal‐bound hydroxide on the phosphorus atom of the substrate, leading to the cleavage of the phosphate‐ester bond. Four exchange‐correlation functionals were used to derive the potential energy profiles in protein environments. Although the enzyme is confirmed to work better as triesterase, as revealed by the barrier heights in the rate‐limiting steps of the catalytic processes, its promiscuous ability to hydrolyze also the product of the reaction has been confirmed. The important role played by water molecules and some residues in the outer coordination sphere has been elucidated, while the binuclear Co^II center accomplishes both structural and catalytic functions. To correctly describe the electronic configuration of the d shell of the metal ions, high‐ and low‐spin arrangement jointly with the occurrence of antiferromagnetic coupling, have been herein considered.     

Indecomposable involutive set-theoretic solutions of the Yang–Baxter equation

We describe the indecomposable involutive non-degenerate set-theoretic solutions of the Yang–Baxter equation as dynamical extensions of non-degenerate left cycle sets. Moreover we characterize the indecomposable dynamical extensions and we produce several examples. As an application we construct a family of finite indecomposable solutions whose structure groups have not the unique product property.     

(ω,c)-asymptotically periodic functions,first-order Cauchy problem,and Lasota-Wazewska model with unbounded oscillating production of red cells

In this paper, we study a new class of functions, which we call (ω,c)-asymptotically periodic functions. This collection includes asymptotically periodic, asymptotically antiperiodic, asymptotically Bloch-periodic, and unbounded functions. We prove that the set conformed by these functions is a Banach space with a suitable norm. Furthermore, we show several properties of this class of functions as the convolution invariance. We present some examples and a composition result. As an application, we prove the existence and uniqueness of (ω,c)-asymptotically periodic mild solutions to the first-order abstract Cauchy problem on the real line. Also, we establish some sufficient conditions for the existence of positive (ω,c)-asymptotically periodic solutions to the Lasota-Wazewska equation with unbounded oscillating production of red cells.     

Immobilization of Distinctly Capped CdTe Quantum Dots onto Porous Aminated Solid Supports

Immobilization of quantum dots (QDs) onto solid supports could improve their applicability in the development of sensing platforms and solid‐phase reactors by allowing the implementation of reusable surfaces and the execution of repetitive procedures. As the reactivity of QDs relies mostly on their surface chemistry, immobilization could also limit the disruption of solution stability that could prevent stable measurements. Herein, distinct strategies to immobilize QDs onto porous aminated supports, such as physical adsorption and the establishment of chemical linking, were evaluated. This work explores the influence of QD capping and size, concentration, pH, and contact time between the support and the QDs. Maximum QD retention was obtained for physical adsorption assays. Freundlich and Langmuir isotherms were used to analyze the equilibrium data. Gibbs free energy, enthalpy, and entropy were calculated and the stability of immobilized QDs was confirmed.     

Pseudo–almost‐periodic solutions for delayed differential equations with integrable dichotomies and bi–almost‐periodic Green functions

Using the existence of integrable bi–almost‐periodic Green functions of linear homogeneous differential equations and the contraction fixed point, we are able to prove the existence of almost and pseudo–almost‐periodic mild solutions under quite general hypotheses for the differential equation with constant delay in a Banach space X, where τ>0 is a fixed constant. The results extend the corresponding ones in the case of exponential dichotomy. Some examples illustrate the importance of the concepts.     

Within‐host and synaptic transmissions: contributions to the spread of HIV infection

We study the contributions of within‐host (virus‐to‐cell) and synaptic (cell‐to‐cell) transmissions in a mathematical model for human immunodeficiency virus epidemics. The model also includes drug resistance. We prove the local and global stability of the disease‐free equilibrium and the local stability of the endemic equilibrium. We analyse the effect of the cell‐to‐cell transmission rate on the value of the reproduction number, R₀. Moreover, we show evidence of a qualitative change in the models' dynamics, subjected to the value of the drug efficacy. In the end, important inferences are drawn. Copyright © 2016 John Wiley & Sons, Ltd.