Relationship Between the J(Sn–C–H) of the Dimethyltin Dichloride Adducts of some Pyridines and Anilines,and the Donor Strength of the Lewis Bases

A study by titrimetric methods of the donor strength of pyridine and aniline and some of their para -substituted derivatives, and the J (¹¹⁹Sn–C–H) of their adducts with dimethyltin dichloride in nitrobenzene, has shown that the p K _b of a Lewis base and its para -substituted derivatives varies linearly with the J (¹¹⁹Sn–C–H) of the adducts of dimethyltin dichloride (Me₂SnCl₂), with the Lewis base dissolved in an inert solvent. A graphical plot of the p K _b of a given series of Lewis bases versus the J (Sn–C–H) of their complexes with Me₂SnCl₂ in nitrobenzene (at the same temperature, and same complex concentration) gives a straight line with a negative gradient, making possible the deduction of the other parameter (e.g. p K _b) for a Lewis base in the series, where the one parameter (e.g. J (Sn–C–H) is known. The graph for each series of Lewis base has its own characteristic gradient, and the gradients appear proportional in magnitude to the donor strengths of each class of the bases, making it possible to deduce from such graphs which series of Lewis bases are the stronger donors.     

Organic solvents as catalysts of formation of phosphorus-containing thiosemicarbazides

The kinetics of the reaction of O,O-diphenyl phosphorohydrazidothioate with phenyl isothiocyanate at 25°C in benzene in the presence of organic bases is studied. The dependences of the catalytic activity on the nature and structure of organic bases and on various parameters characterizing their basicity are analyzed. The catalytic activity exhibited in the formation of phosphorus-containing thiosemicarbazides by donor solvents added to benzene correlates well with both spectroscopic and thermodynamic parameters of basicity: Taft (pK _HB), Koppel-Palm (B), and Gutmann (DN) parameters. A common mechanism of the base catalysis of the thiosemicarbazide formation by organic bases of different classes is suggested and discussed.     

Single-point titrations: Part-I. The determination of bases

Equations are derived for the calculation of acid mixtures, which upon titration with base show a linear relation between pH and the amount of base. Three to five weak acids were used and a linearity of better than ±0.02 pH units was obtained. The use of such mixtures for analysis of the base content of samples by means of a single pH measurement is described. A procedure for obtaining conditional pK_a values of the components of the acid mixture is also described. The single-point titration method is advocated for use when better accuracy than that of direct potentiometry is desired but less than that of an ordinary titration can be accepted. It is not necessary to know the pK_b or the number of weak bases.     

Determination of Lewis Acid Base Properties of Poly(??-n-alkyl) Methacrylates Adsorbed on Silica by Inverse GC

In this paper, the acid base properties in the Lewis terms of poly(??-n-alkyl) methacrylates and when they are adsorbed on silica, were determined. The acid base constants K _A and K _D of various polymers were calculated by testing the classical model and proposed a new model giving K _A and K _D and a third constant K reflecting the amphoteric character of our solid substrates and obtaining more precise and quantified results. When the length of alkyl group in side chain of poly(??-n-alkyl) methacrylates changes, the surface properties of such polymers also change and consequently affect all superficial characteristics and especially the acid base constants and the transition phenomena. It was also proved that the specific enthalpy was directly correlated to the acid base constants, the carbon atom number in the side chain of poly(??-n-alkyl) methacrylates and the acceptor AN and donor DN numbers of electrons of polar organic molecules, by the following relationship: ??H ^sp?=???H ^sp(AN, DN, K _D, K _A, n _SC).     

The learning machine in quantitative chemical analysis: Part 2. Potentiometric titrations of mixtures of three bases

Computer-calculated curves for the titration of mixtures of one strong base and two weak bases are used in the training and testing of a linear learning machine. The results indicate that multicategory classifiers can be calculated from a computer-generated training set of titration curves in which a random error of ±0.01 unit in the pH values is introduced. The relative error in the predictions for concentrations of bases not included in the training set was of the orderof ± 1% for concentration ratios up to 10:1 when δpK_b for the weak bases exceeded 1 pK unit and for K_b1 ? 5 × 10^-4 and K_b2 ? 10^-9. Calculation of the first derivative of the volume of titrant versus pH curves as a preprocessing step was necessary to obtain this accuracy for the weak bases, whereas the volume of titrant versus pH curves had to be used directly in the determination of the strong base. Predictions of concentrations of actual samples were in agreement with the computer-calculated results.     

Cyclodextrin assisted nanophase determination of alkaloid salts

The poor water solubility of the free base and the high dissociation constant (K_a) hinder mainly the assay of alkaloid salts. We have elaborated an enviroment friendly method that can be carried out in aqueous media. The stability difference of the cyclodextrin (CD) complexes of free and protonated bases were used for this purpose. The base is included into the hydrophobic cavity of the CD (which serves as an apolar solvent phase on molecular level) and its solubility in water is increased. Since the base forms more stable inclusion complex than its protonated species, the pK_a is decreased and the potentiometric titration is promoted by this way, too. Six different hydrohalide alkaloid salts have been investigated and the most appropriate CDs were chosen (depending on the size of the molecules and/or substituents). The results of the assays agree well with those obtained by the direct nonaqueous titrations. The stability constants of the inclusion complexes have been also computed.     

Uncertainty estimation in measurement of pKa values in nonaqueous media: A case study on basicity scale in acetonitrile medium

The difficulties in estimating uncertainty of pK_a values determined in nonaqueous media are reviewed and two different uncertainty estimation approaches are presented and applied to the pK_a values of the compounds on a previously established self-consistent spectrophotometric basicity scale in acetonitrile. One approach is based on the ISO GUM methodology (the “ISO GUM” approach) and involves careful analysis of the uncertainty sources and quantifying the respective uncertainty components. The second approach is based on the standard-deviation-like statistical parameter that has been used for characterization of the consistency of the scale (the “statistical” approach). It is demonstrated that the ISO GUM approach somewhat overestimates the uncertainty. The statistical approach is based on long-term within-laboratory statistical data and it is demonstrated that it underestimates the uncertainty. In particular it neglects the laboratory bias effects that are taken into account at least to some extent by the ISO GUM approach. Thus, together these two approaches allow to “bracket” the uncertainties of the pK_a values on the scale. The uncertainties of the pK_a values are defined in two different ways. Definition (a) includes the uncertainty of the pK_a of the reference base (anchor base of the scale) pyridine. Definition (b) excludes it. It is demonstrated that both definitions have their virtues. Definition (a) leads to the uncertainty ranges of 0.12-0.22 and 0.12-0.14 pK_a units at standard uncertainty level for different bases using the ISO GUM and statistical approach, respectively. Definition (b) leads to the uncertainty ranges of 0.04-0.19 and 0.02-0.08 pK_a units, respectively. The uncertainty of the pK_a of a given base is dependent on the quality of the measurements involved and on the distance from the reference base on the scale. The importance of the correlation between the pK_a values of bases belonging to the same scale is stressed.     

Laser raman and infrared spectrum of poly-p-xylylene

The dipole moments μ_ab of some forty complexes between substituted phenols and substituted pyridines were determined, using the Onsager relation. The dipole increment Δμ, vector difference between μ_ab and the dipole moments μ_a and μ_b of the components, show a coherent evolution with the pK_a of the donor and of the acceptor and with the complexation enthalpy, when such orientations of the molecules which correspond to a hydrogen bond between the O-H group of the phenol and the lone pair of electrons of the nitrogen atom of the base are chosen. This evolution with respect to the ΔpK_a is given by a unique curve for all the complexes. This shows that the difference in pK_a between the donor and the acceptor is the main factor determining Δμ for these complexes. This curve presents a sigmoidal aspect in agreement with a model assuming a tautomeric equilibrium between two forms of the hydrogen bond: A-H·B ? A^?·H⁺-B. The corresponding equilibrium constant K_s was computed for the complexes lying in the transition region and obeys the linear relation, log K_s = 0.7pK_a-2.25. The data also permit the evaluation of the angle θ_a between the O-H direction and the dipole moment of the 3,4-dinitrophenol. This angle is of the order of magnitude of 70°, showing the presence of appreciable amounts of different rotamers around the C-O direction in the complexes composed of this acid with pyridines.     

Addition reaction of arylboronic acids to aldehydes and α,β-unsaturated carbonyl compounds catalyzed by conventional palladium complexes in the presence of chloroform

Arylboronic acids react with aldehydes and α,β-unsaturated carbonyl compounds in the presence of a base and a catalytic amount of a palladium(0) complex with chloroform, affording the corresponding addition products in good yields, and chiral benzhydrol was obtained with up to 43% e.e. using (S,S)-bppm as a ligand. General palladium complexes have no catalytic activity without chloroform. Because chloroform is essential for this reaction, these reactions would be promoted by dichloromethylpalladium(II) species.     

Interaction between Glyoxal-bis-(2-hydroxyanil) and Bovine Serum Albumin in Solution

The interaction between glyoxal-bis-(2-hydroxyanil) (GBH) and bovine serum albumin (BSA) was studied by spectroscopic methods including fluorescence spectroscopy, circular dichroism (CD) and UV–visible absorption spectra. The mechanism for quenching the fluorescence of BSA by GBH is discussed. The number of binding sites n and observed binding constant K _b were measured by the fluorescence quenching method. The thermodynamic parameters ΔH ^θ , ΔG ^θ , and ΔS ^θ were calculated at different temperatures and the results indicate that hydrogen bonding and van der Waals forces played major roles in the reaction. The distance r between the donor (BSA) and acceptor (GBH) molecules was obtained according to Förster’s theory of non-radiation energy transfer. Synchronous fluorescence and three-dimensional fluorescence spectra were used to investigate the structural change of BSA molecules that occur upon addition of GBH, and these results indicate that the secondary structure of BSA molecules is changed by the presence of GBH.     

A spectroscopic study of the iodine complexes of donors—pyridines,phenanthrolines, bipyridines and diazines

Ultraviolet—visible spectral data of iodine complexes of n- and π-donors have been interpreted by considering that the repulsion energy responsible for the blue shift of the iodine band is also experienced by the donor partner which causes the blue shift of the original band of the donor. This reasoning explains the spectral data of iodine complexes of benzene, pyridine-N-oxide and stilbazoles. Ultraviolet—vis. spectra of the iodine complexes of pyridine, aminopyridines and diazines have been reinvestigated and discussed in the light of the above reasoning. The above reasoning is extended to the CT spectra of iodine complexes of twin-site donors such as 1,10-phenanthroline, its methyl and chloro derivatives, 1,7 and 4,7-phenanthrolines, 2,2′-bipyridine and 4,4′-bipyridine. Arguments are presented which indicate that the donors used in this study form only 1:1 complexes with iodine. The thermodynamic parameters were evaluated for iodine complexes of the above twin-site donors. The kinetics of transformation of outer CT complexes between the donors and iodine to inner complexes is presented and discussed. Two CT bands are observed for the iodine complexes of 1,10-phenanthroline and its substituents. These bands are explained by assuming a structure for the 1,10-phenanthroline complex in which iodine is in dynamic equilibrium between the two nitrogens.     

pKa values in organic chemistry – Making maximum use of the available data

Acids and bases are ubiquitous. Sometimes, it is essential to know the accurate strength (pK_a values) of the acids/bases to work with, but sometimes just acidity/basicity order is enough. We often receive requests to measure pK_a values of different substances in different solvents for answering questions like “what acids can be used to protonate this substance” or “what base is able to deprotonate that compound?” Such questions can, in fact, often be answered using published pK_a data in different solvents. This digest/tutorial will give an overview of how to make efficient use of the existing pK_a data.     

Interaction of Fluorescein with Felodipine: A Spectrofluorometric and Thermodynamic Study

The interaction between fluorescein and felodipine (FLD) was investigated by the spectrofluorometric method. The fluorescence of FLD was quenched by fluorescein and quenching is in accordance with the Stern-Volmer relation. The binding constants of fluorescein with FLD were obtained at different temperatures. The binding constant and number of binding sites at different temperatures were calculated yielding the corresponding thermodynamic parameters ΔS, ΔH and ΔG. The distance r between the donor (FLD) and acceptor (fluorescein) molecules was obtained according to the fluorescence resonance energy transfer. The optimum conditions for the fluorometric determination of fluorescein were studied and the quenching method was successfully applied to estimate the fluorescein concentration of the pharmaceutical sample directly.     

The SAMPL6 challenge on predicting aqueous p<Emphasis Type="Italic">K</Emphasis><Subscript>a</Subscript> values from EC-RISM theory

The “embedded cluster reference interaction site model” (EC-RISM) integral equation theory is applied to the problem of predicting aqueous pK_a values for drug-like molecules based on an ensemble of tautomers. EC-RISM is based on self-consistent calculations of a solute’s electronic structure and the distribution function of surrounding water. Following-up on the workflow developed after the SAMPL5 challenge on cyclohexane-water distribution coefficients we extended and improved the methodology by taking into account exact electrostatic solute–solvent interactions taken from the wave function in solution. As before, the model is calibrated against Gibbs energies of hydration from the “Minnesota Solvation Database” and a public dataset of acidity constants of organic acids and bases by adjusting in total 4 parameters, among which only 3 are relevant for predicting pK_a values. While the best-performing training model yields a root-mean-square error (RMSE) of 1 pK unit, the corresponding test set prediction on the full SAMPL6 dataset of macroscopic pK_a values using the same level of theory exhibits slightly larger error (1.7 pK units) than the best test set model submitted (1.7 pK units for corresponding training set vs. test set performance of 1.6). Post-submission analysis revealed a number of physical optimization options regarding the numerical treatment of electrostatic interactions and conformational sampling. While the experimental test set data revealed after submission was not used for reparametrizing the methodology, the best physically optimized models consequentially result in RMSEs of 1.5 if only improved electrostatic interactions are considered and of 1.1 if, in addition, conformational sampling accounts for quantum-chemically derived rankings. We conclude that these numbers are probably near the ultimate accuracy achievable with the simple 3-parameter model using a single or the two best-ranking conformations per tautomer or microstate. Finally, relations of the present macrostate approach to microstate pK_a results are discussed and some illustrative results for microstate populations are presented.     

The coulometric titration of acids and bases in m-cresol medium

A method is described for the coulometric titration of acids and bases in the solvent m-cresol. The method is suitable for bases with pK_a values greater than 11 in m-cresol, or for acids with pK_a values below 13 in m-cresol. Amounts of 5–50 μeq of acid or base can be determined with a relative accuracy of ±1%.     

Guest-host interaction and photochemical transformation of silver particles isolated in rare gas matrices

Silver dimers and small clusters isolated in rare gas matrices are studied by UV-VIS absorption, emission, and resonance Raman spectroscopy. One, two, and three dimer trapping sites can be identified in Xe, Kr, and Ar matrices, respectively. The sites are identified by computer simulation to be either ofD _4h symmetry, with the molecules aligned in the 〈100〉-direction of thefcc-host lattice, or ofD _2h symmetry, with the molecules occupying single or double vacancies and aligned in the 〈110〉-direction. Low energy external modes of the dimers are observed in the resonance Raman spectra. They probe the guest-host interaction of the molecules and are assigned to librational modes. Trimers and larger clusters are found to be very photosensitive. Three different trimers can be observed in Xe and Kr matrices, respectively. They can be transformed reversibly into each other by laser irradiation. This indicates that probably three corresponding isomers can get stabilized in the two matrices. Further evidence for this interpretation is obtained from emission spectroscopy. Despite the photosensitivity of the trimers it is possible to stabilize the concentration of a particular species by a dual beam technique. Thus we obtained a resonance Raman spectrum of one species in a Xe matrix and a preresonance spectrum of the corresponding species in a Kr matrix.     

Spectrophotometric and spectroscopic studies of charge transfer complexes of p-toluidine as an electron donor with picric acid as an electron acceptor in different solvents

The charge transfer complexes of the donor p-toluidine with π-acceptor picric acid have been studied spectrophotometrically in various solvents such as carbon tetrachloride, chloroform, dichloromethane acetone, ethanol, and methanol at room temperature using absorption spectrophotometer. The results indicate that formation of CTC in non-polar solvent is high. The stoichiometry of the complex was found to be 1:1 ratio by straight-line method between donor and acceptor with maximum absorption bands. The data are discussed in terms of formation constant (K_CT), molar extinction coefficient (?_CT), standard free energy (ΔG^o), oscillator strength (f), transition dipole moment (μ_EN), resonance energy (R_N) and ionization potential (I_D). The results indicate that the formation constant (K_CT) for the complex was shown to be dependent upon the nature of electron acceptor, donor and polarity of solvents that were used.     

Study on the Binding of Chloride Ion to Hemoglobin Using Electromotive Force Method

The electromotive force of the concentration cell, in which both half‐cells contain the same concentration of sodium chloride, and one of which also contains hemoglobin (Hb), was measured on the isoelectric point of Hb (pH = 6.70). On the basis of Scatchard equation, a stepwise binding model and an improved calculation method were presented. Using the new calculation method, the number of the chloride‐binding sites on Hb molecule and the corresponding binding constants were calculated. The results show that there are three classes of binding groups on a Hb molecule, the number of the binding sites and the corresponding binding constants are n₁ = 1, K⁰₁ = 245; n₂ = 8, K⁰₂ = 3.50; n₃ = 8, K⁰₃ = 1.91, respectively. The factors of influencing the interaction between Cl^? and Hb molecule were clarified, and that the differences between our results and the results of computer modeling, as well as the results of molecular dynamics simulation were also discussed.     

Titrimetric applications of multiparametric curve-fitting : Part 1. Potentiometric titrations of weak bases with strong acids at extreme dilutions

A multiparametric curve-fitting procedure is described for locating the equivalence point of a potentiometric titration and is applied to data obtained in titrations of acetate ion with hydrochloric acid over a wide range of concentrations (down to 6.5 · 10^-5M acetate). It does not depend on the existence of a point of inflection on the titration curve, and therefore yields useful results in titrations of this very weak base at concentrations well below that at which the point of maximal slope disappears. Three parameters are involved: the concentration of the base being titrated, the concentration dissociation constant K_a of its conjugate acid in the medium employed, and the apparent activity coefficient y_H⁺ of hydrogen ion in that medium, and all three of these must be evaluated when a new supporting electrolyte is employed. In 3.0 M potassium chloride at 24°, the apparent activity coefficient of hydrogen ion is 1.746₀, and this value permits data obtained in titrations of other or unknown bases in this medium to be interpreted by two-parameter fits. The value of K_a for acetic acid in this medium is 1.313₄ · 10^-5M; by means of these two numerical values routine titrations of acetate in this medium can be interpreted by one-parameter fits. It is possible to locate the equivalence point with an accuracy and a precision that cannot be approached by other techniques and even to obtain useful and reliable results under conditions so unfavorable that other techniques fail completely.     

Nanocrystalline magnesium oxide as a solid base catalyst promoted one pot synthesis of gem-dichloroaziridine derivatives under thermal conditions

In this study, efficient and mild synthesis of gem-dichloroaziridines from Schiff bases in the presence of nanocrystalline magnesium oxide/chloroform as a novel source of dichlorocarbene intermediate under thermal conditions have been described. The reaction is dramatically enhanced in the presence of nanocrystalline magnesium oxide, and any byproducts were detected during or after the reaction. The corresponding products have been obtained in excellent yields, high purity and short reaction times.