Polarity and strong sensitivity to external electric field in azacrown oligophenylenevinylene.

Complex study of quadrupolar azacrown dye (E,E)-5,5́-Bis[2-(4-(4',7',10',13',16'-pentaoxa-1 azacyclooctadecyl)phenyl)ethenyl]-2,2́-bipyridine 1 was performed. Electronic spectra of absorption and fluorescence in different solvents exhibit strong solvatochromism. Electrooptical absorption measurements (EOAM) were performed to determine the electric dipole moments. These measurements gave large values of dipole moments in the ground µg and Franck-Condon excited state µeFC equal to 6.8 ± 0.14C m and 39.3 ± 0.3C m, respectively. Furthermore, the results of EOAM suggest the existence two conformers in the ground state with close energies of electronic transitions. Density functional theory (DFT) calculations directly show that the shape of this molecule is not planar in the ground state and also allows the existence of two stable conformers with close energies. They appeared due to different orientations of the left and right pyridine fragments of the solute. The energies, electric dipole moments and dependences of dipole moments on the strength of applied electric field were calculated for found stable conformers of 1. DFT calculations with TD / B3LYP / 3-21G and cc-pVDZ (Time Depend) approach show that external electric field increases dramatically the dipole moments of the solute under study. The higher field intensity the larger the excited electric dipole in the range intensities from zero to âˆ¼ 2.8·× 10 9 V/m.

Solvatochromy and symmetry breaking in two quadrupolar oligophenylenevinylenes.

Electrooptical absorption measurements (EOAM), solvatochromic dependences and quantum chemical simulations testify to large dipole moments change of two quadrupolar oligophenylenevinylenes upon transition to Franck-Condon excited state µeFC. The values of the dipole moments µg and µeFC are in the range [(4.2 - 4.9)1030] C m and (30.8 - 47.0)1030C m, respectively. The relations of dipole moments in the ground and excited states determined by EOAM correlate well with results obtained via the solvatochromic method. Calculations carried out by density functional theory (DFT) show that optimized configuration of the ground state of these molecules is not planar. The results from all methods applied unequivocally show the structural symmetry breaking in the studied compounds.

Electrooptical Absorption Measurements (EOAM) Testify Existence of two Conformers of Prodan and Laurdan with Different Dipole Moments in Equilibrium Ground and Franck-Condon Excited State.

The results from the electrooptical absorption measurements (EOAM) on the equilibrium ground and excited Franck-Condon state dipole moments of Prodan and Laurdan in 1,4-dioxane are presented. As follows from experiments Prodan and Laurdan in the equilibrium ground and excited Franck-Condon state have two conformers with considerably different dipole moments. The electrical dipole moments and the transition dipole moment, obtained from the short-wavelength region of the absorption spectrum are parallel. The electrical dipole moments measured at the long-wavelength spectral region are parallel to each other but not parallel to the transition dipole moment m a. The angle θ between the transition dipole moment m a and the dipole moment in the equilibrium ground state µ g of the long-wavelength conformer is about 30(0) for both probes. Obtained results evidence that donor-acceptor pairs of the short-wavelength and long-wavelength conformers are not located on the same axis. Two low-energy conformers of Prodan have been found by density functional theory (DFT) calculations, differing in the orientation of the carbonyl group towards the naphthalene system.

Validation of sun exposure and protection index (SEPI) for estimation of sun habits.

BACKGROUND: In both Sweden and Australia high incidence rates of skin cancer have become a major health problem. In prevention and risk communication, it is important to have reliable ways for identifying people with risky sun habits. In this study the validity and reliability of the questionnaire Sun Exposure Protection Index (SEPI), developed to assess individual's sun habits and their propensity to increase sun protection during routine, often brief, clinical encounters, has been evaluated. The aim of our study was to evaluate validity and reliability of the proposed SEPI scoring instrument, in two countries with markedly different ultraviolet radiation environments (Sweden and Australia). METHOD: Two subpopulations in Sweden and Australia respectively were asked to fill out the SEPI together with the previously evaluated Readiness to Alter Sun Protective Behaviour questionnaire (RASP-B) and the associated Sun-protective Behaviours Questionnaire. To test reliability, the SEPI was again filled out by the subjects one month later. RESULTS: Comparison between SEPI and the questions in the Sun-protective Behaviours Questionnaire, analyzed with Spearman's Rho, showed good correlations regarding sun habits. Comparison between SEPI and RASP-B regarding propensity to increase sun protection showed concurrently lower SEPI mean scores for action stage, but no difference between precontemplation and contemplation stages. The SEPI test-retest analysis indicated stability over time. Internal consistency of the SEPI, assessed with Cronbach's alpha estimation showed values marginally lower than the desired >0.70 coefficient value generally recommended, and was somewhat negatively affected by the question on sunscreen use, likely related to the classic "sunscreen paradox". There were some differences in the performance of the SEPI between the Swedish and Australian samples, possibly due to the influence of "available" sunlight and differing attitudes to behaviour and protection "at home" and on vacation. CONCLUSIONS: SEPI appears to be a stable instrument with an overall acceptable validity and reliability, applicable for use in populations exposed to different UVR environments, in order to evaluate individual sun exposure and protection.

Histaprodifens: synthesis, pharmacological in vitro evaluation, and molecular modeling of a new class of highly active and selective histamine H(1)-receptor agonists.

A new class of histamine analogues characterized by a 3, 3-diphenylpropyl substituent at the 2-position of the imidazole nucleus has been prepared outgoing from 4,4-diphenylbutyronitrile (4b) via cyclization of the corresponding methyl imidate 5b with 2-oxo-4-phthalimido-1-butyl acetate or 2-oxo-1,4-butandiol in liquid ammonia, followed by standard reactions. The title compounds displayed partial agonism on contractile H(1) receptors of the guinea-pig ileum and endothelium-denuded aorta, respectively, except 10 (histaprodifen; 2-[2-(3, 3-diphenylpropyl)-1H-imidazol-4-yl]ethanamine) which was a full agonist in the ileum assay. While 10 was equipotent with histamine (1), methylhistaprodifen (13) and dimethylhistaprodifen (14) exceeded the functional potency of 1 by a factor of 3-5 (13) and 2-3 (14). Compounds 10 and 13-17 relaxed precontracted rat aortic rings (intact endothelium) with relative potencies of 3.3- up to 28-fold (compared with 1), displaying partial agonism as well. Agonist effects were sensitive to blockade by the selective H(1)-receptor antagonist mepyramine (pA(2) approximately 9 (guinea-pig) and pA(2) approximately 8 (rat aorta)). The affinity of 10 and 13-17 for guinea-pig H(1) receptors increased 20- to 100-fold compared with 1. Two lower homologues of 10 were weak partial H(1)-receptor agonists while two higher homologues of 10 were silent antagonists endowed with micromolar affinity for rat and guinea-pig H(1) receptors. In functional selectivity experiments, 10, 13, and 14 did not stimulate H(2), H(3), and several other neurotransmitter receptors. They displayed only low to moderate affinity for these sites (pA(2) < 6). For a better understanding of structure-activity relationships, the interaction of 1 and 10, 13 and 14 within the transmembrane (TM) domains of the human histamine H(1) receptor were studied using molecular dynamics simulations. Remarkable differences were found between the binding modes of 10, 13, and 14 and that of 1. The imidazole ring of 10, 13, and 14 was placed 'upside down' compared with 1, making the interaction of the N(pi)-atom with Tyr431 possible. This new orientation was mainly caused by the space filling substitution at the 2-position of the imidazole ring and influenced the location of the protonated N(alpha)-atom which was positioned more between TM III and TM VI. This orientation can explain both the increased relative potency and the maximum effect of 10, 13, and 14 compared with 1. Compound 13 (methylhistaprodifen; N(alpha)-methyl-2-[2-(3, 3-diphenylpropyl)-1H-imidazol-4-yl]ethanamine) is the most potent histamine H(1)-receptor agonist reported so far in the literature and may become a valuable tool for the study of physiological and pathophysiological H(1)-receptor-mediated effects.

Cationic amphiphiles with G-protein-stimulatory activity: studies on the role of the basic domain in the activation process.

2-Substituted histamines, which are cationic-amphiphilic, activate pertussis toxin-sensitive G-proteins by a receptor-independent mechanism. Lipophilicity is an important determinant for this G-protein activation, but the influence of basicity remained unclear. We prepared four imidazole-containing compounds and nine alkylamines with different basicity and studied their effcts on high-affinity GTP hydrolysis in HL-60 membranes. The substances contained a lipophilic domain (L) and polar (P) and/or cationic (C) domains. Compared to 2-substituted histamines (L-P-C), the corresponding L-C-P type compounds were less potent and effective which, however, were still more active than L-P-P type substances. Among alkylamines, 2-octadecylaminoethyl-N,N-diethylamine (11) was the most potent GTPase activator (pEC50 = 5.7; 100% stimulation above basal). Conversely, 3-(5-hydroxyundecylamino)propylamine (15) was the most efficient compound (pEC50 = 4.3; 160% stimulation above basal). Compared to compounds 11 and 15, which belong to the L-C-C type, the corresponding L-P-C type compounds were less active. Thus, among 2-substituted histamines and alkylamines, a terminal cationic domain is critical for potent and/or effective receptor-independent G-protein activation. An L-C-X structure (X = P or C) is more favorable for G-protein activation than a L-P-X structure. Potency and efficiency of receptor-independent G-protein activators are independently determined drug parameters.