Basicity Constants Research Articles

Experimental and Theoretical Quantitative Studies of the Hydrogen Bonding Basicity of 2,5-Disubstituted Tetrazoles and Some Related Heterocycles.

The tetrazole cycle is a well-known pharmacophore fragment that is part of the structure of a large number of biologically active compounds, including drugs. The diverse biological properties of such heterocylic systems and related compounds are largely determined by their ability to form strong hydrogen bonds with the targets. However, quantitative data on the hydrogen bonding of such heterocycles are limited. In the present article, we have determined the hydrogen bonding basicity constants (pKHB) of a series of 2-substituted-2H-tetrazoles as well as of some 1,5-disubstituted-1H-tetrazoles, 1H-triazoles in 1,1,2,2-tetrachloroethylene by means of FTIR spectroscopy. The influence of the nature of the substituents on the pKHB values of these compounds has been evaluated. Also, the structure of the HB complexes and the theoretically predicted pKHB values have been discussed by means of the DFT approach using the B3LYP/6-311++G(d,p) basis set and CPCM model. It was shown that in the case of 2,5-disubstituted-2H-tetrazoles, the endocyclic nitrogen atom at position 4 is the most preferred basicity center. Thermodynamic parameters of the hydrogen bonding complex formation have been also determined experimentally and calculated by the theoretical method.

ELECTRONEGATIVITY AND STRENGTH OF ACIDS AND BASES IN AQUEOUS SOLUTIONS

Сoncepts of acidity-basicity for systems of different types are considered. The application of the parameter of effective electronegativity for estimating the acidity is proposed, the value of which is calculated from the thermochemical data of acid-base reactions in the condensed state (liquid, solid). The basis is the value of electronegativity of SO3, which should be equal to 3.00. Its values are in the range of 2.0 ÷ 3.1 for acid oxides and 0.3 ÷ 1.6 for oxides of basic nature. A significant group consists of oxides of bifunctional nature (amphoteric oxides) whose electronegativity values are 1.7 ÷ 1.9. A characteristic feature of amphoteric oxides is the manifestation of two values of electronegativity, corresponding to acid and basic functions. It is shown that the behavior of water as a characteristic amphoteric oxide is similar. Some predominance of acidic properties of water over the basic ones is shown and the possible reason for such behavior is discussed. To take into account this phenomenon, a method of converting the electronegativity of water to its value for the oxide partner during hydration is proposed. The values of electronegativity of hydroxides of elements (acidic, basic and amphoteric) were carried out by averaging them for components on the principle of additivity, the correctness of which is confirmed by direct calculations for individual hydroxides. It is shown that in the formation of hydroxides of elements there is a convergence between the values of electronegativities of acidic and basic oxides, ie the reduction of the former and the growth of the latter. Instead, in the case of amphoteric hydroxides, no noticeable changes in electronegativities compared to the original oxides occur. There is a qualitative correlation between the electronegativity of the hydroxides of the elements and the acidity (basicity) constants of their aqueous solutions, which is a reflection of their strength. This allows predicting the strength of acids and bases based on the electronegativity of hydroxides.

Thermodynamic Basicity Constants of Highly Substituted Manganese Porphyrazines and Their Connection to the Structure of Molecules

Thermodynamic Basicity Constants of Highly Substituted Manganese Porphyrazines and Their Connection to the Structure of Molecules

Synthesis, structure and basic properties of 5,10,15,20-tetrakis[4′-(benzoxazole-2-yl)phenyl]-21,23-dithiaporphyrin

The synthesis of 5,10,15,20-tetrakis [4 '- (benzoxazol-2-yl) phenyl] -21,23-dithiaporphyrin was carried out by the reaction of metal complex catalysis. In this work, quantum chemical calculations were performed in the DFT approximation (hybrid functional B3LYP) with a set of 6–21 G basis functions. The resulting compound was identified by electron absorption, 1H NMR spectroscopy and mass spectrometry. The basic properties of heterosubstituted ligand in comparison with the classical porphyrin analogue and unsubstituted TPP were studied by the spectrophotometric titration method in an acetonitrile - perchloric acid system. The basicity constants for the first and second steps and the ranges of existence of the protonated forms of 5,10,15,20-tetrakis [4 '- (benzoxazol-2-yl) phenyl] -21,23-dithiaporphyrin and its classical analog were determined.

Acid–Base Properties of Polyhalogenated Tetraphenylporphyrins

[2,3,7,8,12,13,17,18-Octabromo-5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrinato]zinc(II) and [2,3,7,8,12,13,17,18-octachloro-5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrinato]zinc(II) were synthesized by halogenation of [5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrinato]zinc(II) with N-bromosuccinimide and N-chlorosuccinimide, respectively, in a mixture of chloroform with methanol. Treatment of the halogenated zinc porphyrins with trifluoroacetic acid in chloroform gave the corresponding free ligands. The isolated compounds were identified by electronic absorption, 1H NMR, and mass spectra. The acid–base properties of 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin, 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin, and 2,3,7,8,12,13,17,18-octachloro-5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin were studied in acetonitrile at 298 K. Their acidity and basicity constants and concentration ranges of their ionized forms were determined.

Heteroatomic substitution of tetraphenylporphyrin as approach for regulating coordination ability

The work reports first studied kinetics of complexation between copper and heterosubstituted porphyrins, namely 5,10,15,20-tetraphenyl-21-thiaporphyrin and 5,10,15,20-tetraphenyl-21-oxaporphyrin, as well as comparison with the structural analogue being tetraphenylporphyrin. Spectrophotometric titration allowed for determination of basicity constants characterizing heterosubstituted porphyrins in acetonitrile–perchloric acid. An increasing basicity in the porphyrin series: HSP < H2TPP < HOP for about four orders of magnitude is shown as expected to be accompanied with enhancing coordination ability of the ligands.

Synthesis and Acid–Base Properties of β-Octabromo-Substituted Unsymmetrical Nitrophenylporphyrins

The bromination of [5-(4-nitrophenyl)-10,15,20-triphenylporphyrinato]cobalt(II) and [5,10,15-tris-(4-nitrophenyl)-20-phenylporphyrinato]cobalt(II) with N-bromosuccinimide in a mixture of chloroform and dimethylformamide gave [2,3,7,8,12,13,17,18-octabromo-5-(4-nitrophenyl)-10,15,20-triphenylporphyrinato]-cobalt(II) and [2,3,7,8,12,13,17,18-octabromo-5,10,15-tris(4-nitrophenyl)-20-phenylporphyrinato]cobalt(II). Treatment of the cobalt complexes with a mixture of perchloric and sulfuric acids afforded the corresponding metal-free porphyrins. Electron absorption, 1H NMR, and mass spectra of the synthesized compounds were studied, and acidity and basicity constants of the porphyrin ligands in acetonitrile were determined.

Surface characterization of 1-butyl-1-ethylpiperidinium bromide by inverse gas chromatography

This work addresses the surface characterization of an organic salt based on a piperidinium cation and a halide anion, similar to a first generation ionic liquid, using the Inverse Gas Chromatography (IGC) technique. IGC was employed in order to assess the dispersive surface energy and the acid/base character of 1-butyl-1-ethylpiperidinium bromide, [C2C4PIP]Br at a temperature range (313.15–343.15 K) well below its melting point, where the retention mechanism is governed by the surface adsorption of the probes. This type of characterization was possible due to the high melting point of [C2C4PIP]Br, namely 413.15 K. The dispersive component of the surface energy was estimated with the aid of the Schultz method and the Dorris-Gray method. Results obtained using the first method were higher than the ones obtained by the latter. The discrepancy between the two methods was found to increase with the increase of temperature. The acid/base characterization was implemented by using the Flour and Papirer approach as well as the Brookman and Sawyer method. The acidity and basicity constants of the surface of [C2C4PIP]Br revealed that it is amphoteric with a predominantly basic character.

Thermodynamic Characterization of Surface and Solubility of 5-((S)-3,7-Dimethyloctyloxy)-2-[[[4-(octyloxy)phenyl]imino]methyl]phenol Liquid Crystal with Some Solvents

The inverse gas chromatography method was used to obtain dispersive surface energy, surface acidity or basicity constants, mole fraction activity coefficients of the solvents at infinite dilution f...

Basicity of Highly Substituted β-Octaalkyl-meso-aryl- and -meso-thienyl Porphyrins

5-Phenyl-, 5,15-diphenyl-5,15-di(thiophen-2-yl)-, and 5,10,15,20-tetraphenyloctaalkyl-21H,23H-porphyrins in benzene–acetic acid mixtures are moderate bases (pK–0.27 to–2.48). There is no simple correlation between the basicity constants and any electronic or geometric structure parameter of their molecules due to the contributions of three factors to the basicity: distortion of the planar structure in highly substituted macrocycles and their protonated forms, positive charge delocalization over the conjugated bond system, and electronic effects of substituents.

INFLUENCE OF LIGANDS BASICITY ON COMPLEXATION KINETICS OF 5,10,15,20-TETRA(TRIFLUOROMETHYL)PORPHYN AND 5,10,15,20-TETRA(ISO-BUTYL)PORPHYN WITH COPPER ACETATE

Spectrophotometric studies of base and complexation properties of 5,10,15,20-tetra(trifluoromethyl)porphine and 5,10,15,20-tetra(iso-butyl)porphine were carried out in systems acetonitrile – HClO4 and CH3COOH – Cu(ОАc)2. It was found that under ligands titration with perchloric acid in acetonitrile the consecutive protonating of nitrogen atoms of pyrrolic rings occurs with formation of mono – and dicationic forms. Electron absorption spectra may be obtained for these cationic forms. Total basicity constants and concentration intervals of existence of ligands ionized forms in acetonitrile were determined. Kinetic parameters of copper(II) complex formation was measured. The influence of nature of meso-position substituents of porphyrin macrocycle on reactivity of tetrapyrrolic macrocycle was dicussed.

Thermochemical Properties and Regularities of Amides, Anilides, and Amidic Acids

The thermodynamic properties of carbamide and its alkyl substituted were studied insufficiently. In this article, the enthalpies of combustion of ΔсН of some amides, anilides and amidic acids have been determined experimentally; their standard enthalpies of formation have been calculated. Linear dependences between the average atomic enthalpy of combustion of ΔcH amides and their basicity constants in acidic aqueous solutions of pKBH + have been established; a correlation that relates the enthalpies of combustion of amides and the corresponding amidic acids has been found.

Assessment of tautomer distribution using the condensed reaction graph approach.

We report the first direct QSPR modeling of equilibrium constants of tautomeric transformations (logK T ) in different solvents and at different temperatures, which do not require intermediate assessment of acidity (basicity) constants for all tautomeric forms. The key step of the modeling consisted in the merging of two tautomers in one sole molecular graph ("condensed reaction graph") which enables to compute molecular descriptors characterizing entire equilibrium. The support vector regression method was used to build the models. The training set consisted of 785 transformations belonging to 11 types of tautomeric reactions with equilibrium constants measured in different solvents and at different temperatures. The models obtained perform well both in cross-validation (Q2 = 0.81 RMSE = 0.7 logK T units) and on two external test sets. Benchmarking studies demonstrate that our models outperform results obtained with DFT B3LYP/6-311 ++ G(d,p) and ChemAxon Tautomerizer applicable only in water at room temperature.

One‐scale basicities of diaminobenzenes and diaminonaphthalenes: from aniline to proton sponge

Basicity constants, pKa, for a wide range of mono‐protonated diaminobenzenes and diaminonaphthalenes, including dimethylamino derivatives were for the first time uniformly measured in 20% aqueous ethanol (29 compounds) and 80% aqueous dioxane (39 compounds) spanning from aniline to 1,8‐bis(dimethylamino)naphthalene (‘proton sponge’). The dioxane system proved to be more versatile and because of better solubility of N‐alkylated polyaminoarenes allowed to add to the same scale some superbasic bis(dialkylamino)‐, tetrakis(dialkylamino)‐, and hexakis(dialkylamino)naphthalenes, thus extending the scale for almost 10 pKa units, revealing possible limits of basicity changes in aromatic amines. The basicity of reference bases, pyridine and triethylamine, was also measured in these solvent systems. A group of N‐alkylated compounds was found to be less basic in aqueous dioxane when compared with their NH2‐analogs. This anomaly was not observed in aqueous ethanol. Other basicity trends and correlations between different basicity scales were also discussed. Copyright © 2016 John Wiley &amp; Sons, Ltd.

Poly(N,N-diallylaspartic acid-alt-sulfur dioxide): its synthesis and application

Monomer pairs, dimethyl N,N-diallylaspartate hydrochloride [(CH2=CH–CH2)2NH+CH(CO2Me)CH2CO2Me Cl−] (I)/SO2 and N,N-diallylaspartic acid hydrochloride [(CH2=CH-CH2)2NH+CH(CO2H)CH2CO2H Cl−] (II)/SO2, underwent alternate cyclocopolymerization to give cationic polyelecyrolytes (CPEs), poly(I-alt-SO2) (III) and poly(II-alt-SO2) (IV), respectively, in very good yields. (+) III upon acid hydrolysis was converted to cationic (+) IV, bearing in each repeating unit the triprotic acid residues [(NH+…(CO2H)2] of aspartic acid hydrochloride. Under the influence of pH, (+) IV has been equilibrated to water-insoluble diprotic polyzwitterionic acid (±) V, water-soluble monoprotic poly(zwitterion-anion) (± −) VI and finally its conjugate base polydianion (=) VII. Basicity constants of CO2− and amine group have were determined. The pH-responsive polymer was demonstrated to be an efficient antiscalant against CaSO4 scaling. For potential separation and purification of biomolecules, a recyclable aqueous two-phase system (ATPS) was constructed using water-soluble (=) VII and urethanized polyvinyl alcohol; the ionic polymer can be recycled by precipitating it as (±) V at a lower pH.

A glutamic acid-based polymer keeping intact the integrity of all the three original functionalities of the amino acid

Dimethyl glutamate, on treatment with allyl bromide, afforded dimethyl N,N-diallylglutamate which upon alkaline ester hydrolysis followed by acidification with aqueous HCl gave N,N-diallylglutamic acid hydrochloride [(CH2=CH–CH2)2NH+CH(CO2H)(CH2)2CO2H Cl−] I. Using Butler’s cyclopolymerization protocol, new monomer I underwent ammonium persulfate-initiated polymerization to give pyrrolidine ring-embedded linear cyclopolymer II i.e. −[−CH2(C4H6)NH+{CH(CO2H)(CH2)2CO2H Cl−}CH2−]−n retaining the integrity of all the three functionalities of glutamic acid. Under the influence of pH, the repeating units of triprotic acid (+) in II were equilibrated to those of water-insoluble diprotic polyzwitterionic acid (±) III, water-soluble monoprotic poly(zwitterion-anion) (±−) IV, and its conjugate base polydianion (=) V. The critical salt concentration required to promote water solubility of (±) III has been determined to be 0.548 M NaCl, 0.271 M NaBr, 0.133 M NaI. The basicity constants of the carboxyl groups and trivalent nitrogen in (=) V have been determined. A 5 ppm and 20 ppm concentrations of III are effective in inhibiting the precipitation of CaSO4 from its supersaturated solution with a ≈100% scale inhibition efficiency at 40 °C for a duration of over 3 and 16 h, respectively.

Stimuli-Responsive Hydrogels Bearing amino acid Residues: a Potential Platform for Future Therapies

Vinyl hydrogels bearing α-aminoacid residues have been explored as platforms for the treatment of cancer, glaucoma and mood disorder therapies. Ionic/ionizable groups of the L-valine, L-phenylalanine and L-histidine residues are able to modify the swelling properties of the hydrogel on the basis of their thermodynamic characteristics. Greater basicity constants of functional groups improve a greater loading of the drug and a longer sustained-release pattern. The pH and the temperature affect the swelling of the hydrogel and increase ‘on demand’ the drug availability. A further stimulus based on alternating magnetic fields can be applied on hydrogels containing embedded magnetic nanoparticles used for site-specific controlled drug delivery. The diffusion process for the in vitro release of the drug (cisplatin, doxorubicin, pilocarpine, trazodone, citalopram and paroxetine) from the drugloaded hydrogels is mainly controlled by the drug-polymer interaction, that in the meanwhile preservs it’s bioactivity. The different interaction strength between the drug and the polymer may be a strategy to develop suitable capsules for long-term therapies.

Controlled release of antidepressant drugs by multiple stimuli-sensitive hydrogels based on α-aminoacid residues

Two slightly cross-linked hydrogels bearing l-phenylalanine (Phe-Nip3) or l-valine (Ava2) residues of a copolymeric and homopolymeric vinyl structure were considered for their potential application in the psychiatric treatment of depression. Two antidepressant drugs (citalopram and trazodone) were loaded into hydrogels and their controlled release behavior monitored for several days at 25 °C in two buffer solutions of different pHs (PBS pH 7.4 and acetate pH 4.6). The different basicity constants (logKs) of the involved substance determine a different electrostatic effect between the drug ionized positively and the negatively charged hydrogel. Both the hydrogels loaded with citalopram showed a greater binding effect with respect to trazodone. In fact, for the same hydrogel, the release of citalopram in PBS (4 days) was slower than trazodone (24 h). In addition, at pH (4.6) < logK the release of the drug was much slower and durable, due to the lower capacity of ionization and swelling of the hydrogel. Additionally, the magnetic nanoparticles (CoFe2O4) embedded into the hydrogel Phe-Nip3 were an additional remote control for drug release through the stimulation of an appropriate alternating magnetic field (AMF, 20 kHz and 50 W). In these conditions, the kinetics of the drug released was substantially increased.

Surface Properties of Hyper-Cross-Linked Polymeric Resins Using Inverse Gas Chromatography: Effect of Post-Cross-Linking Solvents

Two series of hyper-cross-linked polymeric resins (hyper-resins) were prepared via post-cross-linking of low-cross-linked macroporous poly(vinylbenzyl chloride-divinylbenzene) (poly(CDVB)) or poly(styrene-divinylbenzene) (poly(DVB)) swollen in the solution of 1,2-dichloroethane or nitrobenzene, respectively. Inverse gas chromatography was used to investigate the effect of post-cross-linking solvents on the surface chemistry of hyper-resins. The dispersive component of the surface free energy (γsd) and surface acid–base character of hyper-resins were estimated using the retention time of different nonpolar and polar probes at the infinite dilution region. Results showed that the values of γsd were basically identical for the hyper-resins prepared using the same precursor; the acidity and basicity constants KA and KD confirmed that the surface of four hyper-resins were Lewis amphoteric with predominantly basic character, but the strength of the surface acidic and basic sites of hyper-resins synthesized usin...

Coordination and acid-base properties of meso-nitro derivatives of β-octaethylporphyrin

Spectrophotometric method is used to study the acid-base and coordination properties of a series of porphyrins with a continuously increasing degree of macrocycle deformation resulting from the introduction of strong electron — withdrawing substituents: 2,3,7,8,12,13,17,18-octaethylporphyrin (1), 5-nitro-2,3,7,8,12,13,17,18-octaethylporphyrin (2), 5,15-dinitro-2,3,7,8,12,13,17,18-octaethylporphyrin (3), 5,10,15-trinitro-2,3,7,8,12,13,17,18-octaethylporphyrin (4), and 5,10,15,20-tetranitro-2,3,7,8,12,13,17,18-octaethylporphyrin (5). It is found that the values of total basicity constants obtained for the investigated compounds consistently diminish with an increase in the number of meso-substituents: 11.85 (1) &lt; 10.45 (2) &lt; 10.31 (3) &lt; 10.23 (4) &lt; 9.56 (5). The values of the combined acidity constants of porphyrins (4–5) obtained in acetonitrile-DBU system at 298 K are pKa = 10.90 and 10.40 respectively. The reaction of complex formation between the porphyrins and their dianionic forms with zinc acetate was studied. It is shown that two opposing factors, the steric and electronic effects of the substituents, change the acid-base and coordination properties of the above series of compounds.