Vibrational Spectroscopic and Molecular Docking Studies of Amrinone, a Cardiotonic Inotropic Drug-=SUP=-*-=/SUP=-

Amrinone is a class I cardiotonic inotropic agent, which is known to increase the cyclic adenosine monophosphate (cAMP) level by inhibiting the phosphodiesterase 3 (PDE3) enzyme. In this study the theoretically possible stable conformations of the amrinone, was examined first by conformational analysis method and then the obtained most stable conformation was optimized by DFT/wb97xd/6-311++G(d,p) level of theory using Gaussian 03 program. The credibility of the theoretical model was confirmed by comparison of experimental and theoretical vibrational spectra of the title molecule. The fundamental vibrational wavenumbers, IR and Raman intensities of the optimized structure of amrinone were determined using DFT/wb97xd/6-311++G(d,p) level of theory and compared with the experimental vibrational spectra. To investigate the influence of amrinone on cAMP enhancement, the docking simulations towards PDE3B were carried out and the main binding interactions of amrinone with PDE3 were elucidated. Cytochrome P450s (CYPs) are very important phase I metabolizing enzymes. The interaction between amrinone and CYPs (CYP1A2, CYP2C9 and CYP2C19) was investigated by docking simulations. Moreover, molecular docking of the title molecule with different proteins and receptors were studied to reveal potential mechanisms for therapeutic applications. Molecular docking simulations revealed that amrinone showed strong binding affinity to integrins α5β1 (Delta G=-6.6 kcal/mol) and αIIbβ3 (-6.6 kcal/mol), and DNA (-6.5 kcal/mol). The results correlated with its anticancer activity. The drug likeness and ADMET properties of amrinone were analyzed for the prediction of pharmacokinetic profiles. Key words: amrinone, DFT calculations, FTIR, Molecular Docking, ADMET.

Less is more? Ultra-low carbohydrate diet and working dogs’ performance

New Zealand farm working dogs are supreme athletes that are crucial to agriculture in the region. The effects that low or high dietary carbohydrate (CHO) content might have on their interstitial glucose (IG) and activity during work are unknown. The goals of the study were to determine if the concentration of IG and delta-g (a measurement of activity) will be lower in dogs fed an ultra-low CHO high fat diet in comparison to dogs fed a high CHO low fat diet, and to determine if low concentrations of IG are followed by reduced physical activity. We hypothesized that feeding working farm dogs an ultra-low CHO diet would reduce their IG concentrations which in turn would reduce physical activity during work. We prospectively recruited 22 farm dogs from four farms. At each farm, dogs were randomized to one of two diets and had a month of dietary acclimation to their allocated diet. The macronutrient proportions as a percentage of metabolizable energy (%ME) for the high CHO low fat diet (Diet 1) were 23% protein, 25% fat, and 52% CHO, and for the ultra-low CHO high fat diet (Diet 2) 37% protein, 63% fat, and 1% CHO. Following the acclimation period, we continuously monitored IG concentrations with flash glucose monitoring devices, and delta-g using triaxial accelerometers for 96 h. Dogs fed Diet 2 had a lower area under the curve (±SE) for IG (AUC Diet 2 = 497 ± 4 mmol/L/96h, AUC Diet 1 = 590 ± 3 mmol/L/96h; P = 0.002) but a higher area under the curve (±SE) for delta-g (AUC Diet 2 = 104,122 ± 6,045 delta-g/96h, AUC Diet 1 = 80,904 ± 4,950 delta-g/96h; P< 0.001). Interstitial glucose concentrations increased as the activity level increased (P < 0.001) and were lower for Diet 2 within each activity level (P < 0.001). The overall incidence of low IG readings (< 3.5 mmol/L) was 119/3810 (3.12%), of which 110 (92.4%) readings occurred in the Diet 2 group (P = 0.001). In the Diet 2 group, 99/110 (90%) of the low IG events occurred during the resting period (19:00–06:00). We conclude that feeding Diet 2 (ultra-low CHO high fat diet) to working farm dogs was associated with increased delta-g despite decreased IG concentrations. Interstitial glucose concentrations were positively associated with dogs’ activity levels independent of diet. Lastly, events of low IG occurred at a low incidence and were predominantly seen between 19:00–06:00 in dogs fed the ultra-low CHO high fat diet.

Impacts of polyols and temperature on the micellization, interaction and thermodynamics behavior of the mixture of tetradecyltrimethylammonium bromide and polyvinyl alcohol

Herein, the aggregation manner of the mixture of polyvinyl alcohol (PVA) and tetradecyltrimethylammonium bromide (TTAB) was performed in polyols (glucose, maltose and galactose) media over 300.55–320.55 K temperatures range with 5 K interval through conductivity measurement method. The micelle formation of TTAB + PVA mixture was identified by the assessment of critical micelle concentration (CMC) from the plots of specific conductivity (κ) versus TTAB concentration. The degree of micelle ionization (α), the extent of bound counter ions (β) as well as thermodynamic properties ( Δ G m 0 ${\Delta}{G}_{m}^{0}$ , Δ H m 0 ${\Delta}{H}_{m}^{0}$ and Δ S m 0 ${\Delta}{S}_{m}^{0}$ ) of TTAB + PVA systems have been estimated. The CMC values reveal that the micelle formation of TTAB + PVA mixture experience an enhancement in the manifestation of polyols. The values of free energy of micellization ( Δ G m 0 ${\Delta}{G}_{m}^{0}$ ) are negative for the TTAB + PVA system in aqueous polyols media, suggesting a spontaneous aggregation phenomenon. The Δ H m 0 ${\Delta}{H}_{m}^{0}$ and Δ S m 0 ${\Delta}{S}_{m}^{0}$ values of TTAB + PVA systems direct that the PVA molecule interacts with TTAB through the exothermic, ion-dipole, and hydrophobic interactions. The thermodynamic properties of transfer were also determined for the move of TTAB + PVA mixture from H2O to water + polyols mixed solvents. The values of compensation temperature (T c) and intrinsic enthalpy gain ( Δ H m 0 , ∗ ${\Delta}{H}_{m}^{0,\ast }$ ) were evaluated and discussed for the studied system.

The Thermodynamics of Copper (II) and Nickel (II)- Diamine Complex Formation in Aqueous Solution

<p>This work describes the accurate measurement of the thermodynamic functions Delta G degree and Delta H degree for the step-wise coordination equilibria between each of the ions H+, Ni2+, Cu2+, and, a series of C1-substituted 1,2-diaminoethanes in aqueous solution. The study Involved. (a) The construction of a sensitive constant temperature environment calorimeter for measuring the enthalpy changes in the complex-formation reactions, (b) The rigorous calibration of an electrode system, incorporating a glass electrode, for the direct potentiometric measurement of equilibrium hydrogen ion concentrations in the solutions containing complex ions. The thermodynamic functions Delta G degree and Delta H degree led to accurate Delta S degree values for the step-wise complex-formation reactions. The thesis considers the contribution of the entropy of ligation to the stability of complex ions. The molar entropies of the complex ions have been calculated and their values considered with respect to the coordination number and the possible structure, degree of hydration and steric properties of the ions.</p>

The Thermodynamics of Copper (II) and Nickel (II)- Diamine Complex Formation in Aqueous Solution

<p>This work describes the accurate measurement of the thermodynamic functions Delta G degree and Delta H degree for the step-wise coordination equilibria between each of the ions H+, Ni2+, Cu2+, and, a series of C1-substituted 1,2-diaminoethanes in aqueous solution. The study Involved. (a) The construction of a sensitive constant temperature environment calorimeter for measuring the enthalpy changes in the complex-formation reactions, (b) The rigorous calibration of an electrode system, incorporating a glass electrode, for the direct potentiometric measurement of equilibrium hydrogen ion concentrations in the solutions containing complex ions. The thermodynamic functions Delta G degree and Delta H degree led to accurate Delta S degree values for the step-wise complex-formation reactions. The thesis considers the contribution of the entropy of ligation to the stability of complex ions. The molar entropies of the complex ions have been calculated and their values considered with respect to the coordination number and the possible structure, degree of hydration and steric properties of the ions.</p>

Interaction of cationic surfactant with acid yellow dye in absence/presence of organic and inorganic additives: conductivity and dye solubilization methods

In the present study, the conductometric and dye-solubilization techniques have been utilized to investigate the interaction between an anionic dye (acid yellow 23 [AY]) and a cationic surfactant (cetyltrimethylammonium bromide [CTAB]) in presence of organic (ethanol)/inorganic (NaCl) additives. From the conductometric method, two critical micelle concentrations (cmc) were found for AY + CTAB mixture in an aqueous system and the cmc values were found to undergo a change with the variation of AY concentrations. The cmc values of AY + CTAB systems were observed higher in the alcoholic medium, while the same was found to be lower in the NaCl solutions. The change in cmc of AY + CTAB systems shows an U-like curve with an increase of temperature. The negative free energy of micellization ( Δ G m o ${\Delta}{G}_{m}^{o}$ ) for the AY + CTAB systems has indicated a spontaneous micelle formation in all of the cases studied. The enthalpy ( Δ H m o ${\Delta}{H}_{m}^{o}$ ), as well as the entropy of micellization ( Δ S m o ${\Delta}{S}_{m}^{o}$ ) for the AY + CTAB systems, were assessed and discussed with proper reasoning. Additionally, the enthalpy-entropy compensation parameters were also investigated and illustrated. The solubility of AY and C D was observed to rise linearly with an increase in the concentration of CTAB/NaCl solution. The solubilization capacity (χ) of AY, the molar partition coefficient (K M) amongst the micellar and the aqueous phase, and free energy of solubilization ( Δ G S o ${\Delta}{G}_{S}^{o}$ ) were evaluated and discussed in detail. The former parameters undergo an increase with an increase of NaCl concentrations.

Sharp Minimum Degree Conditions for the Existence of Disjoint Theta Graphs

In 1963, Corrádi and Hajnal showed that if $G$ is an $n$-vertex graph with $n \ge 3k$ and $\delta(G) \ge 2k$, then $G$ will contain $k$ disjoint cycles; furthermore, this result is best possible, both in terms of the number of vertices as well as the minimum degree. In this paper we focus on an analogue of this result for theta graphs. Results from Kawarabayashi and Chiba et al. showed that if $n = 4k$ and $\delta(G) \ge \lceil \frac{5}{2}k \rceil$, or if $n$ is large with respect to $k$ and $\delta(G) \ge 2k+1$, respectively, then $G$ contains $k$ disjoint theta graphs. While the minimum degree condition in both results are sharp for the number of vertices considered, this leaves a gap in which no sufficient minimum degree condition is known. Our main result in this paper resolves this by showing if $n \ge 4k$ and $\delta(G) \ge \lceil \frac{5}{2}k\rceil$, then $G$ contains $k$ disjoint theta graphs. Furthermore, we show this minimum degree condition is sharp for more than just $n = 4k$, and we discuss how and when the sharp minimum degree condition may transition from $\lceil \frac{5}{2}k\rceil$ to $2k+1$.

Psychometric analysis of the Brazilian-version Kidscreen-27 questionnaire

Background The objective of this study was to verify the reliability, discriminatory power and construct validity of the Kidscreen-27 questionnaire in Brazilian adolescents. Methods Adolescents that participated of the pilot study (210 adolescents; 52.9% boys; 13.7 years old) and of the baseline (816 participants; 52.7% girls; 13.1 years old) of the Movimente Project in 2016/2017 composed the sample of the present study. This project was carried out in six public schools in the city of Florianópolis, Santa Catarina, Brazil. Test–retest reproducibility was assessed by the intraclass correlation coefficient and Gwet coefficient; internal consistency through McDonald's Omega; Hankins' Delta G coefficient verified the scale's discriminatory power and; confirmatory factor analysis to assess construct validity. Results Reproducibility values ranged from 0.71 to 0.78 for the dimensions (ICC), and ranged from 0.60 to 0.83 for the items (Gwet). McDonald's Ômega (0.82–0.91) for internal consistency measures. Discriminatory power ranging from 0.94 for the dimension Social Support and Friends to 0.98 for Psychological Well-Being. The factorial loads were > 0.40, except for item 19 (0.36). The fit quality indicators of the model were adequate (X2[df] = 1022.89 [311], p < 0.001; RMSEA = 0.053 (0.049–0.087); CFI = 0.988; TLI = 0.987), confirming the five-factor structure originally proposed. Conclusions The Brazilian-version Kidscreen-27 achieved good levels of reproducibility, internal consistency, discriminatory power and construct validity. Its use is adequate to measure the health-related quality of life of adolescents in the Brazilian context.

The (2,1)-total number of near-ladder graphs

A $(2,1)$-total labelling of a simple graph $G$ is a function $\pi \colon V(G)\cup E(G) \to \{0, \ldots, k\}$ such that: $\pi(u) \neq \pi(v)$ for $uv \in E(G)$; $\pi(uv) \neq \pi(vw)$ for $uv, vw \in E(G)$; and $|\pi(uv)-\pi(u)| \geq 2$ and $|\pi(uv)-\pi(v)| \geq 2$ for $uv \in E(G)$. The $(2,1)$-total number $\lambda_2^t(G)$ of $G$ is the least $k$ for which $G$ admits such a labelling. In 2008, Havet and Yu conjectured that $\lambda_2^t(G)\leq 5$ for every connected graph $G \not\cong K_4$ with $\Delta(G) \leq 3$. We prove that, for near-ladder graphs, $\lambda_2^t(G)=5$, verifying Havet and Yu's Conjecture for this class.

On Asymmetric Colourings of Claw-Free Graphs

A vertex colouring of a graph is asymmetric if it is preserved only by the identity automorphism. The minimum number of colours needed for an asymmetric colouring of a graph $G$ is called the asymmetric colouring number or distinguishing number $D(G)$ of $G$. It is well known that $D(G)$ is closely related to the least number of vertices moved by any non-identity automorphism, the so-called motion $m(G)$ of $G$. Large motion is usually correlated with small $D(G)$. Recently, Babai posed the question whether there exists a function $f(d)$ such that every connected, countable graph $G$ with maximum degree $\Delta(G)\leq d$ and motion $m(G)>f(d)$ has an asymmetric $2$-colouring, with at most finitely many exceptions for every degree. We prove the following result: if $G$ is a connected, countable graph of maximum degree at most 4, without an induced claw $K_{1,3}$, then $D(G)= 2$ whenever $m(G)>2$, with three exceptional small graphs. This answers the question of Babai for $d=4$ in the class of~claw-free graphs.