The study of the lipophilicity of alpha-(4-phenylpiperazin-1-yl)-gamma-phthalimidobutyramides using chromatographic and computational methods

The lipophilicity of the series of alpha-(4-phenylpiperazin-1-yl)-gamma-phthalimido-butyramides (1-8) has been investigated. Several methods, like reversed-phase thin-layer chromatography and high-performance liquid chromatography using reversed-phase RP18 and IAM.DD2 columns, were applied to determine RMO, log k0 and log k(0IAM) factors. The RP-TLC investigations were performed in mixtures of acetone-water and acetonitrile-water. For RP-HPLC method mixtures of acetonitrile, water and 0.01% TFA were used as the mobile phases while for IAM.DD2 investigations mixtures of acetonitrile and water were applied. The partition coefficients of compounds (1-8) were also calculated with the Pallas and CAChe programs. All the obtained data, both from experimental methods and computational calculations, were compared and a suitable conclusion was reached.     

Determination of lipophilicity of alpha-(4-phenylpiperazine) derivatives of N-benzylamides using chromatographic and computational methods

This paper describes the evaluation of lipophilicity of alpha-(4-phenylpiperazine) derivatives of N-benzylamides. We employed reversed-phase thin-layer chromatography (RP-TLC) and reversed-phase high performance liquid chromatography (RP-HPLC) as experimental methods, using mixtures of acetonitrile and water as the mobile phases with addition of 0.1%TFA in the HPLC experiments. Retention parameters (R(M)) and capacity factors (log k) determined by applying these methods were linearly dependent on the acetonitrile concentration and enabled us to estimate the relative lipophilicity factors: R(M0) and log k(0). These factors were compared with the calculated partition coefficients C log P obtained using several software packages. The results indicate that both experimental methods (RP-TLC and RP-HPLC) yielded similar results, and these methods enable determining the lipophilicity of alpha-(4-phenylpiperazine) derivatives of N-benzylamides. Significant correlations were found between log P values calculated by Pallas, ALOGPS and C log P Chem3D programs and the experimental data.     

Synthesis of betulin derivatives and the determination of their relative lipophilicities using reversed‐phase thin‐layer chromatography

A series of superlipophilic or highly lipophilic semisynthetic betulin derivatives was prepared and their relative lipophilicity was measured by reversed‐phase thin‐layer chromatography (RP‐TLC) at different pH values using 1,4‐dioxane–acetate buffer mixtures as mobile phases. Cholesterol, 17β‐estradiol and pure betulin were used as the reference compounds. Linear relationships were found between R_M values and 1,4‐dioxane concentrations in the mobile phases. LogP values were also calculated with computer programs ACD/LogP (ChemSketch 11.0, Advanced Chemistry Development Inc.) and ClogP (Daylight Chemical Information Systems Inc.). The empirical and theoretical data were compared, and the R_M0 values correlated well with logP. Two of the synthesized betulin derivatives are reported for the first time. Copyright © 2009 John Wiley & Sons, Ltd.     

Estimating the lipophilicity of a number of 2‐amino‐1‐cyclohexanol derivatives exhibiting anticonvulsant activity

The lipophilicity of a number of N‐acyl derivatives of trans‐ or cis‐: racemic, (1R,2R)‐ or (1S,2S)‐aminocyclohexanol (1–13) exhibiting anticonvulsant activity was investigated. Their lipophilicity (R_{m 0}) was determined using reversed‐phase thin‐layer chromatography (RP‐TLC) with mixtures of methanol and water as mobile phases. The partition coefficients of compounds 1–13 (log P) were also calculated using two computer programs (Pallas and Chem DU) and compared with R_{m 0}. Copyright © 2009 John Wiley & Sons, Ltd.     

The lipophilicity estimation of 5-arylidene derivatives of (2-thio)hydantoin with antimycobacterial activity

The lipophilicity of antituberculotic 5-arylidene derivatives of (thio)hydantoin, thioacetazone and isoniazid has been determined by reversed-phase thin-layer chromatography (RP-TLC). Mixtures of acetone and water (with acetone content 60-85%) were used as the mobile phase. The R(M) (relative lipophilicity) of each compound (except isoniazid) decreased linearly with the increasing concentration of acetone. The partition coefficients (log P) of the compounds were calculated by the use of eight computer programs (ClogP, KowWin, XlogP, AlogPs, CAChe, Pallas, Interactive analysis and Slipper) and compared with the experimental lipophilicity (R(M0)). According to the observations the best tools for in silico predicting log P of (2-thio)hydantoins are programs KowWin and AlogPs.     

Determination of the lipophilicity of some aniline derivatives by reversed-phase thin-layer chromatography. The effect of the organic phase in the eluent

Summary The lipophilicity of aniline and 36 ring-substituted aniline derivatives was determined by reversed-phase thin-layer chromatography using methanol, acetone and acetonitrile as the organic phase. The R_M value of each compound linearly decreased with increasing concentration of the organic solvent, Acetonitrile showed the highest and methanol the lowest solvent strength, however, the difference between the solvent strength of methanol and acetone was negligible. The site of the substitution considerably influenced the lipophilicity particularly in the case of –NO₂ groups. Good correlation was found between the R_M value extrapolated to zero organic phase concentration and the partition coefficient between n-octanol:water. The change in the R_M value caused by a 1% increase of the organic phase concentration also correlated with the partition coefficient, however, it was of secondary importance. The lipophilicity parameters determined by reversed-phase thin-layer chromatography correlated to a lesser extent with the calculated lipophilicity values of aniline derivatives.     

Heuristic molecular lipophilicity potential (HMLP): a 2D-QSAR study to LADH of molecular family pyrazole and derivatives

The quantum chemical and structure-based technique heuristic molecular lipophilicity potential (HMLP) is used in the liver alcohol dehydrogenase (LADH) study of molecular family pyrazole and derivatives. The molecular lipophilic index LM, molecular hydrophilic index HM, lipophilic indices lss, and hydrophilic indices hss of the substitutes (fragments), and atomic lipophilicity indices las are constructed and used in QSAR study. The HMLP indices are correlated with bioactivities of 18 pyrazole derivatives according to the 2D QSAR procedure. The multiple linear regression equation between the bioactivities of pyrazole derivatives and HMLP indices are built using partial least square (PLS) with the optimal statistical quantity (r=0.987, s=0.479, F=47.19). The inhibition mechanism of LADH of the pyrazole derivatives is explained according to the physical meaning of HMLP indices. During the HMLP calculations for the 2D QSAR, the only input parameters are the atomic van der Waals radius without the need to resort to any empirical parameters. Accordingly, HMLP can provide a rigorous theoretical approach with a crystal clear physical meaning for the 2D QSAR.     

Determination of the lipophilicity of some aniline derivatives by reversed-phase thin-layer chromatography. The effect of salts

Summary The lipophilicity of aniline and 36 ring-substituted aniline derivatives was determined by reversed-phase thin-layer chromatography using NaCl, KCl, MgCl₂, CaCl₂, AlCl₃ and tetramethyl-ammoniumhydroxide, either adsorbed on the silica surface before impregnation or added to the eluent. In most cases the salts decreased the retention power of silica resulting in enhanced mobility of the aniline derivatives. The monovalent cations had the lowest, while AlCl₃ and tetramethylammoniumhydroxide had the highest impact on selectivity. This phenomenon can be explained by the different ion charges. The correlation between the R_M values and the partition coefficient between n-octanol: water were in all cases inferior to those obtained in salt-free systems this means that the presence of salts modifies differently the lipophilicity of aniline derivatives.     

HPTLC and magnetochromatography of new complexes of carboxylates with transition metals or rare earth elements and their ligands – study of lipophilicity

Nineteen new complexes of carboxylates with transition and rare elements as central ions and their ligands were characterized by chromatographic analyses. The parameter of relative lipophilicity (R _M0) of the tested compounds was determined experimentally by the reversed‐phase high‐performance thin layer chromatography method with mixtures of various organic modifiers (acetonitrile, acetone, dioxane) and water as a mobile phase. The extrapolated R _M0 values were compared with the logP values calculated from the molecular structures of tested solutes. Similarities between the lipophilicity indices were analysed by principal component analysis and linear regression. Thin‐layer chromatography combined with a magnetic field has been proposed as a complementary method for determination of lipophilicity of the investigated compounds. The chromatograms in the field and outside it were developed simultaneously in two identical chromatographic chambers. One of them was placed in the external magnetic field of 0.4 T inductivity. We proved that chelation causes a drastic change in compound lipophilicity, but all complexes did not exhibit enhanced activity as compared with the parent ligand. Also in the magnetic field the retention of some complexes changed, which means that the presence of the field influences the physicochemical properties of the compounds and their interactions with the stationary phase.     

On the origin of the lack of anticonvulsant activity of some valpromide derivatives

Two closely related N-substituted valpromide derivatives: N-valproyl glycinamide and N-valproyl glycine are comparatively analyzed, the first of which is antiepileptic active whereas the second is not. The study is based on a conformational analysis using an AM1 Hamiltonian that not only search for the lower energy structures of each derivative but also for the energy involved in their mutual interconversion. Open structures have been compared with cyclic ones, the latter including those stabilized by either inter or intra molecular hydrogen bonds (dimers and monomers, respectively). H-bond formation has been also evaluated by means of ab initio G94(6–31+G(d,p)) calculations for a smaller system (N-formylglycine/glycinamide) modeling both vacuum and solvent conditions. The conformational and electronic characteristics of the open and cyclic monomers, as well as of the dimer N-valproyl glycinamide and N-valproyl glycine structures are discussed. On the basis of the results of their comparative analysis, we have redefined the pharmacophore previously proposed for N-substituted valpromides [Tasso, Bruno-Blanch, Estiu, Int. J. Quant. Chem. 65 (6), 1107 (1997)], relaxing some of the associated requirements. The corrected model requires one carbon atom or any bioisosteric substituent in an anticlinal conformation relative to the aminic nitrogen of the amide moiety, in addition to one hydrogen atom that should be antiperiplanar to the carbonyl oxygen. This model offers an explanation to the different response of N-valproyl glycinamide and N-valproyl glycine against convulsion, which is based on conformational restrictions. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 70: 1127–1136, 1998     

Application of RP-TLC technique for the determination of dissociation constants of 1-substituted pyrrolidin-2-one derivatives

The procedures for measuring dissociation constants (pK(a)) of twenty 1-substituted pyrrolidin-2-one derivatives are described. The dissociation constants of the compounds tested were determined using potentiometric titration, reversed-phase thin-layer chromatography (RP-TLC) and calculated using Pallas and Marvin programs. It was found that the RP-TLC method of determination of pK(a) could be considered as a feasible alternative to potentiometric titration. The Marvin program is a better tool for preliminary estimation of dissociation constant than the Pallas one.     

Determination of lipophilicity of γ‐butyrolactone derivatives with anticonvulsant and analgesic activity using micellar electrokinetic chromatography

The lipophilicity of a library of 30 derivatives of dihydrofuran‐2(3H)‐one (γ‐butyrolactone) was determined by MEKC. Calibration curve prepared for ten reference drugs enabled to calculate partition coefficient (log P) for novel compounds. The results of MEKC analysis were compared with lipophilicity coefficients determined by RP‐TLC (R_M0) and computational (Mlog P, Clog P) methods. Good correlation was observed between the results obtained by both experimental methods: the MEKC parameters log k and relative lipophilicity R_MO. The relationship between determined log P values and results of the computational prediction was weaker. Analysis of the relationship between lipophilicity and anticonvulsant activity showed statistically significant differences between mean values of log P coefficients for group of active (2.18) and inactive (1.51) compounds in the maximal electroshock test.     

A DFT study on the radical scavenging activity of hydroxyanthraquinone derivatives in rhubarb

The structural and electronic properties of hydroxyanthraquinone derivatives in rhubarb, namely, chrysophanol, emodin, physcion, aloe‐emodin, rhein, and their radicals were investigated at density functional level. The bifurcated hydrogen bond property of the studied structures was investigated using the atoms in molecules theory. It turned out that the presence of the dihydroxy functionality increases the radical stability through hydrogen bonds formation and favors hydrogen atom abstraction. Bond dissociation energy and ionization potential were also determined to know if the radical scavenging activity of these compounds proceeds via an H‐atom or an electron‐transfer mechanism. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Synthesis of some substituted benzimidazoles with potential antimicrobial activity

Summary The synthesis andin vitro antimicrobial evaluation of several benzimidazole derivatives with different heterocyclic nuclei at position-2 are described.

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Synthese einiger substituierter Benzimidazole mit potentieller antimikrobieller Aktivität

Zusammenfassung Die Synthese und antimikrobielle Prüfung einiger Benzimidazole mit verschiedenen heterozyklischen Substituenten in 2-Stellung wird beschrieben.

     

Electrochemical reduction of some 3-aryl-2-cyanothioacrylamide derivatives at the DME

Summary The polarographic behaviour of the title compounds is reported and discussed in acid media. The obtained data indicate that these compounds undergo a four-electron reduction. A mechanism for the electrode process atpH<7 is proposed, discussed and clarified via identification of controlled potential electrolysis (CPE) product and application of cyclic voltammetry (CV).

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Die elektrochemische Reduktion einiger 3-Aryl-2-cyanothioacrylamid-Derivate an der DME

Zusammenfassung Es wurde das polarographische Verhalten der Titelverbindungen in saurem Medium untersucht. Die erhaltenen Daten zeigen, daß diese Verbindungen eine Vierelektronenreduktion eingehen. Es wird ein Mechanismus für den Elektrodenprozess beipH<7 vorgeschlagen und diskutiert. Zur Klärung der Verhältnisse wurden die mittels kontrollierter Potential-Elektrolyse (CPE) erhaltenen Produkte identifiziert und auch cyclische Voltammetrie eingesetzt.

     

A theoretical study for the structure of propranolol and some fluorinated derivatives

This paper reports on studies of the theoretical geometrical structure of propranolol and three of its fluorinated derivatives: 1-(2,2,2-trifluoroethylamino)-3-(1-naphthyloxy)-2-propanol [trifluoroethyl-propranolol], 1-(2,2,3,3.3-pentafluoropropylamino)-3-(1-naphthyloxy)-2-propanol [pentafluoropropyl-propranolol], and 1-(2,2,3,3,4,4,4-heptafluorobutylamino)-3-(1-naphthyloxy)-2-propanol [heptafluorobutyl-propranolol]. The semiempirical method AM1 was used to optimize the structures. In the minimum energy state the geometries of the naphthyl moiety and the non-fluorinated portions of the analogs are quite similar to that of the parent. Dipole moments, charge density distributions, and electrostatic potential distributions all point to the significance of the ether oxygen in all four compounds and the increasing contribution of the side-chain terminal to the activity of the molecule with increasing number of fluorines.     

Solid-state linear-dichroic IR-spectroscopy of isophorone derivatives with potential non-linear optical application

Possibilities of linear-dichroic infrared (IR-LD) spectroscopy based on oriented solid samples as suspension in nematic liquid crystal have been applied for detailed experimental IR-band assignment and structural information of 2-[5,5-dimethyl-3-(2-phenyl-vinil)-cyclohex-2-enylidene]-malononitrile, 2-[5,5-dimethyl-3-[2-(2-methoxyphenyl)vinyl]cyclo-hex-2-enylidene]malononitrile and 2-[3-[2-(2,4-dimethoxyphenyl)vinyl]-5,5-dimethylcyclohex-2-enylidene]malononitrile. The data of last two compounds have been compared with known crystallographic ones, thus determining the validity of conclusions made.     

Synthesis of some sulfonamide derivatives with potential antibacterial activity

Some new quinoxaline-6-sulfonamide and phthalazine-6-sulfonamide derivatives were synthesized. The majority of the prepared compounds showed antibacterial activity.Faculty of Pharmacy, University of Tanta, Egypt. Fax: 002 040 335466Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 523–528, April, 2000.