Information-theoretic indices usage for the prediction and calculation of octanol-water partition coefficient.
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The paper describes the new prediction method of octanol-water partition coefficient, which is based on molecular graph theory. The results obtained using the new method are well correlated with experimental values. These results were compared with the ones obtained by use of ten other structure correlated methods. The comparison shows that graph theory can be very useful in structure correlation research. (+info)
Lipophilicity measurement of drugs by reversed phase HPLC over Wide pH range using an alkaline-resistant silica-based stationary phase, XBridge Shield RP(18).
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We propose a reversed phase HPLC (RP-HPLC) with an alkaline-resistant silica-based stationary phase, XBridge Shield RP(18), for the determination of the lipophilicity of drugs with diverse chemical nature ranging from acidic to basic. A set of 40 model compounds with well-defined solvatochromic parameters was selected to allow a broad distribution of structural properties. The chromatographic results showed that the lipophilicity index log k(w) obtained with XBridge Shield RP(18) was well correlated with experimental log P(oct) values (r(2)=0.96). Linear solvation free-energy relationship (LSER) analyses revealed that the retention mechanism of the stationary phase and 1-octanol/water partitioning were controlled by almost the same balance of intermolecular forces (hydrophobicity as expressed by the van der Waals volume V(w), H-bond acceptor basicity beta, and dipolarity/polarizability pi*). The results showed that XBridge Shield RP(18) phase overcomes the shortcomings of the silica-based stationary phases, the application of which to lipophilicity measurements had been limited to neutral and acidic compounds. (+info)
Actions of n-alcohols on nicotinic acetylcholine receptor channels in cultured rat myotubes.
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1. The actions of the n-alcohols from pentanol to dodecanol on nicotinic acetylcholine receptor (nAChR) channels were investigated by recording single ACh-activated channel activity from inside-out membrane patches isolated from cultured rat myotubes. Alcohols were applied to the cytoplasmic side of the membrane; aqueous concentrations ranged from 11.7 mM-pentanol to 0.02 mM-dodecanol. 2. The intermediate-chain alcohols (pentanol to octanol) caused channel currents to fluctuate between the fully open and closed state level so that openings occurred in bursts interrupted by brief gaps. Closed time distributions were fitted well with two exponential components, the fast component representing the closures within a burst. The number of gaps within a burst was dependent on alcohol concentration whereas gap duration was independent of concentration but increased with increasing chain length of the alcohol up to octanol. 3. Nonanol and decanol reduced the mean duration of bursts of openings but did not cause an increase in the number of short closed intervals within a burst. Beyond decanol there was a decline in the ability of the n-alcohols to affect channel function. A saturated solution of undecanol (0.07 mM) reduced the mean open time by 33 +/- 17%, whereas a saturated solution of dodecanol had no significant effect. 4. The current integral per burst was reduced by all the n-alcohols between pentanol and undecanol. The IC50S were as follows: hexanol, 0.53 +/- 0.14 mM; heptanol, 0.097 +/- 0.02 mM; octanol, 0.04 mM and nonanol, 0.16 +/- 0.035 mM. 5. The results were analysed in terms of an open channel block model with a long-lived closed-blocked state beyond the blocked state. Over the range of concentrations tested this describes the effects of all the n-alcohols (C5 to C12) on channel gating reasonably well. 6. Blocking rate constants (k+B) for pentanol through to nonanol were calculated to be between 2.8 and 5.7 X 10(6) M-1 S-1. These values are based on the assumption that the concentration of the alcohols at their site(s) of action was equal to the aqueous concentration applied to the membrane. 7. Equilibrium dissociation constants (KD), calculated from the blocking and unblocking rate constants (KD = k-B/k+B), decreased with increasing chain length from 8 mM for pentanol to 0.15 mM for octanol. The standard free energy per methylene group for adsorption to the site of action was calculated to be about -3.3 kJ mol-1.(ABSTRACT TRUNCATED AT 400 WORDS) (+info)
Adsorption of actives in ophthalmological drugs for over-the-counter on soft contact lens surfaces.
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The adsorption of various kinds of ionic/nonionic actives, added in ophthalmological drugs (artificial tear, contact lens wetting solution, eye-drops, and eyewash) for over-the-counter (marketable drugs with no need of any medical prescription) , on soft contact lens (SCL) surfaces has been studied as a function of hydrophobicity of the actives. The common logarithm of the 1-octanol/water partitioning coefficient (AC_log P) has been used in order to normalize the hydrophobicity of the actives employed in this study. No significant adsorption occurs for relatively hydrophilic actives, whereas the adsorption rate is gradually increased with an increase in the hydrophobicity of the actives. This suggests that the adsorption is predominantly governed by the hydrophobic interaction of the actives with the SCL surfaces, although an electrostatic interaction plays an additional role for the adsorption. The most effective adsorption occurs in the following active-lens combinations: cationic actives--the anionic and hydrated lens IV (methacrylic acid-based SCL); anionic actives---the nonionic and hydrated lens II (N-vinyl pyrrolidone-based SCL); and nonionic actives--the anionic and less-hydrated lens III (containing hydrophobic silicone monomers). (+info)
Evolution of a polymodal sensory response network.
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Three distinct amine receptors operating at different levels within the locomotory circuit are each essential for the serotonergic modulation of chemosensation in Caenorhabditis elegans.
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