Principal component analysis of polarity and interaction parameters in inverse gas chromatography

Inverse gas chromatography is used in the characterization of aliphatic-aromatic and aromatic ketones, their oximes, and ketone-oxime or oxime-oxime mixtures. All these organic materials are used as liquid stationary phases in gas chromatographic columns. A series of polarity and Flory-Huggins interaction parameters are determined and used to describe the physicochemical properties of examined materials, metal extractants, and products of their degradation. Principal component analysis (PCA) is performed on a data matrix consisting of polarity and interaction parameters for ketones, their oximes, and mixtures. The calculations are carried out on the correlation matrix. It is found that seven principal components account for more than 95% of the total variance in the data, indicating that the polarity (interaction) parameters are not correlating well. Physical meanings are attributed to the principal components, the most influential ones being that the first and the second principal components account for several Flory-Huggins interaction parameters, whereas the fifth is correlated with criterion "A". The plots of component loadings show characteristic groupings of polarity indicators, whereas that of component scores show several groupings of stationary phases. Cluster analysis provides mainly the same groupings. PCA allows for the grouping of polarity and solubility parameters based on the information carried within those parameters. There is no need to use more than one parameter from each cluster. McReynolds polarity and the partial molar excess Gibbs free energy of solution per methylene group carry the same information. The groups of ketones, oximes, and their mixtures can be distinguished with the use of PCA on the basis of the measured polarity, solubility parameters, or both.     

新型黄烷酮类衍生物的合成、杀菌活性及定量构效关系研究

设计合成了14个含不同性质取代基的黄烷酮类化合物,并采用核磁共振氢波谱、质谱和元素分析对所有化合物的结构进行了表征.在系统测定化合物对水稻稻瘟病抑制活性的IC₅₀值的基础上,采用Hansch-Fujita方法和CoMFA方法对其定量结构活性关系进行了系统研究,结果发现,化合物的疏水性质、极化效应以及最高空轨道能级对杀菌活性有重要影响,化合物的疏水参数越小,分子越容易极化,则化合物的杀菌活性越高.此外,最高空轨道能级越低,化合物越容易接受电子,其杀菌活性也相应提高.通过考察∑π、clgP以及lgK与化合物杀菌活性的相关性,发现lgK能较好地反映该类化合物的疏水效应.三维定量构效关系研究表明,B环2,3,4位上含有较大体积的取代基,而6位含较小体积的取代基,有利于提高其杀菌活性.     

Conformational analysis of p-tert-butylcalix[4]arene derivatives with trans-alkyl substituents on opposite methylene bridges: destabilization of the cone form by axial alkyl substituents

The stereochemistry of calix[4]arenes substituted by a pair of identical alkyl substituents in a trans fashion at two distal bridges is analyzed. MM3 calculations suggest that increasing the bulk of the alkyl group at the bridges destabilizes those conformations possessing an axial disposition of the substituent. In contrast to the 1,3-dimethyl ether of p-tert-butylcalix[4]arene, which adopts a cone conformation, solution NMR data indicate that the 1,2-alternate conformation is preferred in the dimethyl ether derivatives 5b (alkyl = i-Pr) and 5c (alkyl = t-Bu). In the derivative substituted by the less bulky methyl substituent (5a), both the cone and 1,2-alternate forms coexist in CDCl3. Increasing the polarity of the solvent increases the relative population of the cone form of 5a and 5b. The steric destabilization ensuing from the presence of the axial substituent is so large in the cone conformation of 5c that the 1,2-alternate conformer is the major form even in polar solvents. The cone --> 1,2-alternate interconversion barrier of 5a is 18.2 kcal mol(-1), indicating that the presence of an axial methyl group both destabilizes the cone conformation and decreases its rigidity.     

Multivariate analysis of chromatographic retention data and lipophilicity of phenylacetamide derivatives

One of the most important physicochemical parameters of a molecule that determines its bioactivity is its lipophilicity. Cluster analysis (CA), principal component analysis (PCA), and sum of ranking differences (SRD) were used to compare the lipophilic parameters of twenty phenylacetamide derivatives, obtained experimentally as chromatographic retention data in the presence of different solvents and calculated by different mathematical methods. All the applied methods of multivariate analysis gave approximately similar grouping of the studied lipophilic parameters. In the attempt to group the investigated compounds in respect of their lipophilicity, the obtained results appeared to be dependent on the applied chemometric method. The CA and PCA, grouped the compounds on the basis of the nature of the substituents R₁ and R₂, indicating that they determine to a great extent the lipophilicity of the investigated molecules. Unlike them, the SRD method could not be used to group the studied compounds on the basis of their lipophilic character.     

Déplacements chimiques induits en RMN par un réactif lanthanidique: I—Application á l'analyse conformationnelle de sulfites cycliques

The chemical shifts induced by Eu(fod)₃ in several series of 6-membered cyclic sulfites give the parameters K_c and Δ_SR of the complexation equilibrium for an assumed 1:1 stoicheiometry. The equilibrium constant K_c decreases with increasing bulk of the C-4 and C-6 substituents and polarity of the C-5 substituent, which corresponds to the increase of the i.r. stretching frequency vS?O. Thus axial S?O will be more tightly complexed than equatorial S?O. It can be predicted that when a conformational equilibrium exists without shift reagent, displacement towards an axial S?O form will occur with the reagent. Use of the Δ_SR pseudocontact equation confirms the following: (i) ax S?O chair forms are stabilized; (ii) eq S?O chairs with two eq C-4 and C-6 substituents show an equilibrium with a few percent of the ax S?O flexible conformation, particularly in the absence of an ax C-5 substituent; (iii) twist forms with a 2–5 axis, intermediate S?O and trans-4, 6-di-tert-Bu substituents give a boat form with O at the prow and ax S?O; (iv) the conformational equilibrium of trans-5-tert-butyl-2-oxo-1, 3, 2-dioxathiane (chair with ax tert-Bu and S?O ? 70%) is completely displaced towards that form; (v) cis-4,4,6-trimethyl-2-oxo-1,3,2-dioxathiane, which exists as an equilibrium in which the three types of S?O occur, is complexed essentially in the twist form with a 1–4 axis and ax S?O. Most of these results are supported by the coupling constants analysis for the ratio R₀/S₀ = 1.     

Microwave synthesis under solvent-free conditions and spectral studies of some mesoporphyrinic complexes

A series of A?B and A? type mesoporphyrinic complexes were synthesized with superior yields using microwave irradiation under solvent-free conditions. The structures of the complexes were confirmed using elemental analysis, FT-IR, UV-Vis, EPR and NMR spectral data. The influence of environmental polarity on spectral properties of the mesoporphyrinic complexes was investigated. The obtained results indicate that the shape of absorption and fluorescence spectra does not depend on the solvent polarity under the experimental conditions used. The small shifts of the absorption and emission maximums that occur by increasing of solvent polarity reflects the physical interaction between the porphyrinic substituents and the solvent molecules.     

Hyperconjugation and the increasing bulk of OCOCX3 substituents in trans-1,4-disubstituted cyclohexanes destabilize the diequatorial conformer

The trans diesters of 1,4-cyclohexanediol with a number of acetic acid analogues, CX3COOH, of varying steric hindrance and polarity (CX3 = Me, Et, iso-Pr, tert-Bu, CF3, CH2Cl, CHCl2, CCl3, CH2Br, CHBr2, CBr3) were synthesized, and the axial,axial/equatorial,equatorial conformational equilibria were studied by low-temperature 1H NMR spectroscopy in CD2Cl2. The structures and relative energies of the axial,axial and equatorial,equatorial conformers were calculated at both the MP2/6-311G* and the MP2/6-311+G* levels of theory, and it was only by including diffuse functions that a good correlation of deltaG(o)calcd vs deltaG(o)exptl could be obtained. Both the structures and the energy differences of the axial,axial and equatorial,equatorial conformers are discussed with respect to the established models of conformational analysis, viz., steric 1,3-diaxial and hyperconjugative interactions. Interestingly, the hyperconjugative interactions sigma(C-C)/sigma(C-H) --> sigma*(C-O), together with a steric effect which also destabilizes the equatorial,equatorial conformers on increasing bulk of the substituents, proved to dominate the position of the conformational equilibria. In addition, the preference of the axial,axial conformers with respect to their equatorial,equatorial analogues was greater than expected from the conformational energies of the corresponding substituents in the monosubstituted cyclohexyl esters. The reason for this very interesting and unexpected result is also discussed.     

Effect of substitution on the antimycobacterial activity of 2-(substituted benzyl)sulfanyl benzimidazoles, benzoxazoles, and benzothiazoles--a quantitative structure-activity relationship study

A set of 1160 minimum inhibitory concentration (MIC) values evaluating effect of substitution on the antimycobacterial activity of the previously published 2-(substituted benzyl)sulfanyl benzimidazoles, benzoxazoles, and benzothiazoles has been analyzed by the methods of multidimensional analysis (exploratory analysis, 2D-nonlinear mapping (NLM), principal component analysis (PCA), factor analysis (FA), multiple linear regression (MLR)). The antimycobacterial activity of 2-(subst. benzyl)sulfanyl derivatives of benzimidazole (BIM), 5-methylbenzimidazole (5-Me-BIM), benzoxazole (BOZ), and benzothiazole (BTZ) increased in the order of BTZ相似文献   

The effect of substituents and polymer media on photochromism kinetics of indolinospironaphthoxazine

The effect of substituents in indoline moiety and polymer media on photochromism and thermal decay processes of spirooxazine (ASP) was investigated. The thermal decoloration rate was decreased with increasing steric hindrance of substituents in l-position of indoline moiety. The stability of the colored forms was improved when the hydrogen in the 5-position of indoline moiety was replaced with electron-donating groups and was decreased when substituted by electron-withdrawing groups. In addition, the stability of the colored forms was related to properties of polymer media. The thermal decay rate decreased with an increase in the polarity and rigidity of polymer media. The themal decay kinetics of the colored forms obeyed biexponential decay law.     

Constituents with independence from growth temperature for bacteria using pyrolysis-gas chromatography/differential mobility spectrometry with analysis of variance and principal component analysis

Four bacteria, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus warneri, and Micrococcus luteus, were grown at temperatures of 23, 30, and 37 degrees C and were characterized by pyrolysis-gas chromatography/differential mobility spectrometry (Py-GC/DMS) providing, with replicates, 120 data sets of retention time, compensation voltage, and ion intensity, each for negative and positive polarity. Principal component analysis (PCA) for 96 of these data sets exhibited clusters by temperature of culture growth and not by genus. Analysis of variance was used to isolate the constituents with dependences on growth temperature. When these were subtracted from the data sets, Fisher ratios with PCA resulted in four clusters according to genus at all temperatures for ions in each polarity. Comparable results were obtained from unsupervised PCA with 24 of the original data sets. The ions with taxonomic features were reconstructed into 3D plots of retention time, compensation voltage, and Fisher ratio and were matched, through GC-mass spectrometry (MS), with chemical standards attributed to the thermal decomposition of proteins and lipid A. Results for negative ions provided simpler data sets than from positive ions, as anticipated from selectivity of gas phase ion-molecule reactions in air at ambient pressure.     

Structure-Lipophilicity and Structure-Polarity relationships of amino acids and peptides

The objectives of this study were to gain insights into the structure-lipophilicity relationships of peptides and to propose an improved model for estimating their lipophilicity. First, existing databases were extended to obtain the distribution coefficients of a total of 208 free or protected peptides (di- to pentapeptides). The polarity parameters (Λ) of 23 free amino acids and 19 protected amino acids (AcNH? CHR? CONH₂) and of their side chains were calculated from experimental distribution coefficients and computed molecular volumes. An analysis of the polarity parameters revealed that the hydrophobicity of the amino-acid side chains is largely reduced due to the polar field of the backbone. The polarity parameters of the peptides were then obtained in a similar manner and shown to be highly correlated with the sum of the polarity parameters of their side chains, i.e., the lipophilicity of peptides can be calculated from their molecular volume and the sum of their side-chain polarities using the regression established for each individual series of peptides (Fig. 1). This last restriction is essential since the polarity and lipophilic increment of a NH? C*H? CO unit were shown to decrease with increasing length of backbone.     

Synthesis and Photophysical Properties of a Series of Dimeric Indium Quinolinates

A novel class of quinolinol-based dimeric indium complexes (1–6) was synthesized and characterized using ¹H and ¹³C(¹H) NMR spectroscopy and elemental analysis. Compounds 1–6 exhibited typical low-energy absorption bands assignable to quinolinol-centered π–π* charge transfer (CT) transition. The emission spectra of 1–6 exhibited slight bathochromic shifts with increasing solvent polarity (p-xylene < tetrahydrofuran (THF) < dichloromethane (DCM)). The emission bands also showed a gradual redshift, with an increase in the electron-donating effect of substituents at the C5 position of the quinoline groups. The absolute emission quantum yields (Φ_PL) of compounds 1 (11.2% in THF and 17.2% in film) and 4 (17.8% in THF and 36.2% in film) with methyl substituents at the C5 position of the quinoline moieties were higher than those of the indium complexes with other substituents.     

Influence of droplet size, capillary-cone distance and selected instrumental parameters for the analysis of noncovalent protein-ligand complexes by nano-electrospray ionization mass spectrometry

It has been suggested in the literature that nano-electrospray ionization (nano-ESI) mass spectrometry better reflects the equilibrium between complex and free protein in solution than pneumatically assisted electrospray ionization (ESI) in noncovalent interaction studies. However, no systematic studies of the effects of ionization conditions have been performed to support this statement. In the present work, different instrumental and sample-derived parameters affecting the stability of noncovalent complexes during analysis by nano-ESI were investigated. In general, increased values of parameters such as drying gas flow-rate, ion-source temperature, capillary tip voltage and buffer concentration lead to a dissociation of ribonuclease A (RNAse)-cytidine 2'-monophosphate (CMP) and cytidine 5'-triphosphate (CTP) complexes. The size of the electrosprayed droplets was shown to be an important issue. Increasing the capillary to cone distance yielded an increased complex to free protein ratio when a hydrophilic ligand was present and the reverse effect was obtained with a hydrophobic ligand. Important in this regard is the degree of sampling of ions originating from late-generation residue droplets, that is, ions present in the droplet bulk. Sampling of these ions increases with longer capillary-cone distance (flight time). Furthermore, when the sample flow-rate was increased by increasing the capillary internal tip i.d. from 4 to 30 microm, a decreased complex to free protein ratio for the RNAse-CTP system was observed. This behavior was consistent with the change in surface to volume ratio for flow-rates between 2 and 100 nl min(-1). Finally, polarity switching between positive and negative ion modes gave a higher complex to free protein ratio when the ligand and the protein had the same polarity.     

Phosphorus–nitrogen rotation barriers: Further studies

Phosphorus–nitrogen rotation barriers have been determined by low temperature NMR methods in a variety of compounds of the type RP(X)NR₂′. The observed activation parameters are concentration and solvent independent. Increasing the bulk of substituents on nitrogen increases the barrier. Phosphonamidous fluorides (X = F) have lower barriers than the corresponding chlorides (X = Cl). Increasing the bulk of substituents on phosphorus decreases the barrier.     

Preliminary communication - The effect of a substituent in the central ring on the liquid crystalline properties of di(4-alkoxycarbonylphenyl) terephthalates

Four series of di(4-alkoxycarbonylphenyl) terephthalates with different lateral substituents in the central ring and lengths of the terminal alkyl groups were synthesized. The influence of the lateral substituent on thermodynamical parameters of the phase transitions and elastic properties of the nematic phases (ratio of bend elastic constant to diamagnetic anisotropy K3/Delta chi) were studied by polarizing optical microscopy, differential scanning calorimetry and observations of the Freedericksz transition. It was found that increasing the alkyl chain length and the substituent size in the sequence H, Cl, Br, NO2 results in reduction in stability of the crystal and (as frequently observed in other cases) the liquid crystal phases. The changes in the bend elastic constant and the melting enthalpy caused by the substituent variation are correlated with each other, a fact that is explained by the dependence of short-range lamellar packing on size and polarity of substituent.     

Phase Equilibria of Methoxydimethyloctylsilane,Tetramethyldioctyldisiloxane in Organic Solvents

Abstract The phase diagrams and partial solubility parameters for methoxydimethyloctyl silane (MDOS), tetramethyl dioctyl disiloxane (TDDS), and several organic components were determined. The solubility limits were established by quantitative analysis and compared to the refractive index of known single phase mixtures. The partial solubility parameters were used to provide a qualitative analysis of the phase equilibria. The results showed the phase equilibria depended on the polarity and hydrogen bonding characteristics of the solvents. The solubility of TDDS was reduced with increasing polarity/hydrogen bond character of the amphiphiles solvents.     

Monitoring Fluorescence Response of Amphiphilic Flapping Molecules in Compressed Monolayers at the Air–Water Interface

The air–water interface, which is the boundary of two phases with a large difference in polarity, gives a distinct environment compared with bulk water or air. Since the interface provides a field for various biomolecules to work, it is important to understand the molecular behaviors at the interface. Here, polarity‐independent flapping viscosity probes (FLAP) equipped with hydrophobic/hydrophilic substituents have been synthesized and studied at the air–water interface. In situ fluorescence (FL), which is related to the internal motion and orientation, of three different FLAPs were investigated at the interface, and the internal motion of the molecule was indicated to be suppressed at the interface. In addition, the molecular response was compared with that of conventional viscosity probes (molecular rotors), which indicates the different behaviors of FLAP probably due to the distinct molecular orientation as well as molecular motion.     

Equilibrium distribution of permeants in polyelectrolyte microcapsules filled with negatively charged polyelectrolyte: the influence of ionic strength and solvent polarity

The effects of ionic strength and solvent polarity on the equilibrium distribution of fluorescein (FL) and FITC-dextran between the interior of polyelectrolyte multilayer microcapsules filled with negatively charged strong polyelectrolyte and the bulk solution were systematically investigated. A negatively charged strong polyelectrolyte, poly(styrene sulfonate) (PSS), used for CaCO3 core fabrication, was entrapped inside the capsules. Due to the semipermeability of the capsule wall, a Donnan equilibrium between the inner solution within the capsules and the bulk solution was created. The equilibrium distribution of the negatively charged permeants was investigated by means of confocal laser scanning microscopy as a function of ionic strength and solvent polarity. The equilibrium distribution of the negatively charged permeants could be tuned by increasing the bulk ionic strength to decrease the Donnan potential. Decreasing the solvent polarity also could enhance the permeation of FL, which induces a sudden increase of permeation when the ethanol volume fraction was higher than 0.7. This is mainly attributed to the precipitation of PSS. A theoretical model combining the Donnan equilibrium and Manning counterion condensation was employed to discuss the results.     

Coupling of an advanced tri-functional building block by reductive amination leads to a protected backbone of a new archetype of foldamer

In order to advance our project to explore a new archetype of foldamer that preferentially folds in water, we designed two types of tri-functional building blocks with increasingly favorable ketone deprotection properties. Both were selected for their ease of synthetic access and the availability of bulk starting material. While the first building block proved unsuitable for efficient coupling by reductive amination, the second gave rise to almost quantitative yields according to mass spectral monitoring. It was thus effectively turned into a protected dimer and a tetramer. Although their subsequent purification prior to exhaustive ketone deprotection was preparatively impractical in view of their high polarity/water solubility, the stage is now set for transfer of the oligomer synthesis onto the solid phase on resin in view of the efficient five-step synthetic access from affordable bulk material, the favorable deprotection properties, the perspective for introduction of a variety of backbone substituents, and the possibility to protect the amine terminus by Boc or Fmoc protection.