Colour change and tautomerism of some azo-indicators on complex formation with cyclodextrins

Complex formation of methyl orange and some other azobenzene derivatives with cyclodextrins has been studied in acidic and alkaline solutions by a spectrophotometric method. A correlation has been established between the stability constants of the complexes, the spectral changes accompanying complex formation and a tautomeric equilibrium between protonation on the azo and dimethylamino group. Our own results have been compared with some literature data, and equilibrium constants for the tautomeric rearrangement have been calculated. It has been demonstrated that the significant colour changes observed with the protonated forms only (and not with the corresponding bases) is really caused by a shift of the tautomeric equilibrium.     

四苯基卟啉衍生物质子化热力学

用光度法六种四苯基卟啉衍生物的表 观质子化常数及质子化热力学函数,并用半经验量子化学计算方法PM3计算了卟啉环中两个氮原子（ ＝N－）的净电荷,探讨了取代基的电子效应及空间效应对质子化常数的影响。     

Potentiometric and ab initio studies of acid-base interactions of substituted 4-halo(Cl, Br)pyridine N-oxide systems

By using the potentiometric method, acidity constants have been determined in systems of tri- and tetra-substituted pyridine N-oxides. The potentiometric measurements in systems of four 4-chloropyridine N-oxide derivatives containing the chlorine atom at position 4 to the NO₂ group and four bromine counterparts were carried out in polar non-aqueous solvents, viz. amphiprotic methanol (MeOH) and aprotic protophilic dimethyl sulfoxide (DMSO). It was found that in all the systems studied the pK_a values were readily determinable (as indicated by small standard deviations) in MeOH, whereas in DMSO large standard deviations were obtained making the pK_a values either hardly determinable or indeterminable from potentiometric measurements. Furthermore, it was demonstrated that the acidity constants of protonated N-oxides studied in MeOH changed according to the sequence of their acidity constants in water. It was also found that in the polar solvents studied, i.e. in the amphiprotic methanol and the highly basic aprotic dimethyl sulfoxide, the cationic homo-conjugation equlibrium constants could not be determined using potentiometric method. Also, by using ab initio methods at the RHF and MP2 levels and the PCM model, utilizing the Gaussian 6-31++G^∗∗ basis set, energies and Gibbs free energies of the protonation reactions of the N-oxides have been determined. The energy parameters have been compared with acidity constants of the protonated N-oxides determined by potentiometric titration in methanol to establish a correlation between these approaches.     

Nitrogen bridgehead compounds. Part 69. Studies on quinolizine derivatives. Part 3. Infrared and 1H NMR spectroscopic studies of quinolizine derivatives and their monocyclic tautomers

Infrared and ¹H nmr spectra of 4-oxo, 1 , and 4-imino, 2 , quinolizine derivatives or their monocyclic tautomers 3, 4 have been comparatively studied. The number of ethoxycarbonyl groups, the signals of the hetero proton, the C(9)-H, and the C(6)-CH₃ group in the ¹H nmr spectrum, moreover the N-H stretching vibration bands proved to be diagnostically important for monocyclic or bicyclic as well as for 4-oxo or 4-imino structures. A weak intramolecular hydrogen bridge in compounds 2b and 2f , a strong chelate type hydrogen bridge in 4E and 4F=G could have been demonstrated as well.     

Protonation of 1,2-disubstituted imidazolines and other products of condensation of 2-ethylhexanoic acid with diethylenetriamine and triethylenetetramine

The protonation constants for the products of condensation of 2-ethylhexanoic acid with diethylenetriamine or triethylenetetramine were determined by potentiometric titration. The sequence of protonation of the nitrogen atoms in the imidazoline ring was found from the UV, IR, and ¹³C NMR spectra.     

Synthesis,Potentiometric and 1H NMR Study of Protonation and Complex Formation of 1,4,7-Triazacyclononane-1,4-Diacetate

Abstract

Protonation constants and the protonation scheme of 1,4,7-triazacyclononone-1,4-diacetate (NO2A) have been determined by pH potentiometry and ¹H NMR techniques; shielding constants valid for the entire pH range have been calculated. It has been pointed out that the most basic site in the molecule is the unsubstituted secondary amino group. The first two protonation steps belong to ring nitrogens, the third and fourth ones to the carboxylates; the last nitrogen is protonated in very acidic solutions only. Stability constants of complexes of NO2A with selected divalent and trivalent metal ions were determined; with them no indication of kinetic inertness was found. In NO2A complexes the relative contribution of the triazacyclononane ring to the log K _ML values is greater for soft than for hard metal ions, compared to corresponding values for 1,4,7-triazacyclononane-1,4,7-triacetate.     

The problem of the tautomerism of 2-iminothiazolidin-4-one and some of its derivatives

IR spectroscopy is used to investigate imino-amine tautomerism of 2-iminothiazoliin-4-one and 2-phenyl (p-tolyl, benzyl)imino derivatives of thiazolidin-4-one. It is shown that in the crystalline state 2-iminothiazolidin-4-one exists in the 2-imino form, while in solution (chloroform) it exists in the amino form. 2-Phenyl- and 2-p-tolylimino derivatives of thiazolidin-4-one exist in the imino form, while 2-benzyl-iminothiazolidin-4-one exist in the amino form.     

Nitrogen bridgehead compounds. Part 70. Studies on quinolizine derivatives. Part 4. Ultraviolet-visible spectra and chemical properties of some quinolizine derivatives and their monocyclic tautomers

Ultraviolet-visible spectra of 4-oxo 1 and 4-imino 2 quinolizines or their monocyclic tautomers 3, 4 have been studied in neutral, acidic and basic ethanolic solution as well as in dimethyl sulfoxide and chloroform. Ring B of 4-oxo and 6-unsubstituted 4-imino compounds can be cleaved by sodium ethanolate more or less easily. Ring B of 6-methyl-4-iminoquinolizines is very unstable and they are present mainly in the monocyclic form which are partly dissociated in ethanol and dimethyl sulfoxide especially in higher dilution or in the presence of sodium ethanolate. In dilute acidic ethanol or chloroform, the dissociation is suppressed and in the latter solvent and in some cases, absorption bands can be observed due to a small amount of the 4-imino-6-methylquinolizines. In acidic solution of compounds 3B=C, 3D, 4E, 4F=G having simultaneously cyano and ethoxycarbonyl groups in 1 and 3 position, not simple reprotonation occurs but irreversible changes can be observed.     

5-cyanoimino-4-oxomethylene-4,5-dihydroimidazole and nitrosative guanine deamination. A theoretical study of geometries, electronic structures, and N-protonation

The 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazole 1 (R = H), its N1-derivatives 2 (R = Me) and 3 (R = MOM) and their cyano-N (4, 6, 8) and imino-N protonated (5, 7, 9) derivatives were studied with RHF, B3LYP, and MP2 theory. Solvation effects were estimated with the isodensity polarized continuum model (IPCM) at the MP2 level using the dielectric constant of water. Carbodiimide 10, cyanamide 12, N-cyanomethyleneimine 13, and its protonated derivatives 14 and 15 were considered for comparison as well. Adequate theoretical treatment requires the inclusion of dispersion because of the presence of intramolecular van der Waals, charge-dipole, and dipole-dipole (including H-bonding) interactions. All conformers were considered for the MOM-substituted systems, and direct consequences on the preferred site of protonation were found. The vicinal push (oxomethylene)-pull (cyanoimino) pattern of the 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazoles results in the electronic structure of aromatic imidazoles with 4-acylium and 5-cyanoamido groups. The gas-phase proton affinities of 1-3 are over 30 kcal/mol higher than that for N-cyanomethyleneimine 13, and this result provides compelling evidence in support of the zwitterionic character of 1-3. Protonation enhances the push-pull interaction; the OC charge is increased from about one-half in 1-3 to about two-thirds in the protonated systems. In the gas phase, cyano-N protonation is generally preferred but imino-N protonation can compete if the R-group contains a suitable heteroatom (hydrogen-bond acceptor, Lewis base). In polar solution, however, imino-N protonation is generally preferred. Solvation has a marked consequence on the propensity for protonation. Whereas protonation is fast and exergonic in the gas phase, it is endergonic in the polar condensed phase. It is an immediate consequence of this result that the direct observation of the cations 8 and 9 should be possible in the gas phase only.     

Analysis of host-assisted guest protonation exemplified for p-sulfonatocalix[4]arene--towards enzyme-mimetic pKa shifts

The pD dependence of the complexation of p-sulfonatocalix[4]arene (CX4) with the azoalkanes 2,3-diazabicyclo[2.2.1]hept-2-ene (1), 2,3-diazabicyclo[2.2.2]oct-2-ene (2), 2,3-diazabicyclo[2.2.3]non-2-ene (3), and 1-methyl-4-isopropyl-2,3-diazabicyclo[2.2.2]oct-2-ene (4) in D(2)O has been studied. The pD-dependent binding constants, determined by (1)H NMR spectroscopy, were analyzed according to a seven-state model, which included the CX4 tetra- and penta-anions, the protonated and unprotonated forms of the azoalkanes, the corresponding complexes, as well as the complex formed between CX4 and the deuteriated hydronium ion. The variation of the UV absorption spectra, namely the hypsochromic shift in the near-UV band of the azo chromophore upon protonation, was analyzed according to a four-state model. Measurements by independent methods demonstrated that complexation by CX4 shifts the pK(a) values of the guest molecules by around 2 units, thereby establishing a case of host-assisted guest protonation. The pK(a) shift can be translated into improved binding (factor of 100) of the protonated guest relative to its unprotonated form as a result of the cation-receptor properties of CX4. The results are discussed in the context of supramolecular catalytic activity and the pK(a) shifts induced by different types of macrocyclic hosts are compared.     

1H, 13C and 15N NMR assignments of phenazopyridine derivatives

Phenazopyridine hydrochloride (1), a drug in clinical use for many decades, and some derivatives were studied by one- and two-dimensional (1)H, (13)C and (15)N NMR methodology. The assignments, combined with DFT calculations, reveal that the preferred protonation site of the drug is the pyridine ring nitrogen atom. The chemoselective acetylation of phenazopyridine (2) and its influence on the polarization of the azo nitrogen atoms were evidenced by the (15)N NMR spectra. Molecular calculations of the phenazopyridines 2-4 show that the pyridine and phenyl groups are oriented in an antiperiplanar conformation with intramolecular hydrogen bonding between the N-b atom and the C-2 amino group preserving the E-azo stereochemistry.     

Electronic absorption study on acid-base equilibria for some keto and thioketo pyrimidine derivatives. Experimental and theoretical evidence of enolization and solute-solvent interactions

The UV-vis spectra of recently synthesized 1-amino-5-benzoyl-4-phenyl-1H-pyrimidine-2-one, (I), and 1-amino-5-benzoyl-4-phenyl-1H-pyrimidine-2-thione (II), were studied in aqueous methanol (5%, v/v, methanol) and pure methanol. The nature of the electronic transitions and the role of carbonyl oxygen of I and thiocarbonyl sulfur of II in the behavior of the observed UV-vis spectra were discussed. The carbonyl group at position 2 of I and the thiocarbonyl group of II were found to be enolized instead of protonation. Quantum chemical calculations showed agreement with the experimental evidence. However, the carbonyl group of the benzoyl moiety at position 5 of both compounds underwent neither enolization nor protonation. Acid-base equilibria of the compounds against varying pH have been examined in detail. The pKa values of all related equilibria were determined at room temperature and an ionic strength of 0.10 M from the pH-dependence of the absorbance values using the Henderson-Haselbalch equation and graphical logarithmic analysis. The mean acidity constants for the protonated forms of the compounds were determined as pKa1=4.214 and pKa2=6.678 for I and pKa1=3.739 and pKa2=6.258 for II. The mean acidity constants (pKa3) for the enol form of I and the thioenol form of II were determined as 11.278 and 11.063, respectively. The preferred dissociation mechanisms were discussed based on the data of UV-vis spectroscopy and a mechanism was proposed for each compound. The formation of intramolecular and intermolecular hydrogen bonding were found with I but not with II. The intramolecular bonding stabilizing the enol form was favoured at pH values corresponding to pKa1 and above. On the other hand, the intermolecular hydrogen bonding stabilizing the free form of the carbonyl group was favoured at all pH values.     

Basicity comparison for di-substituted 4-nitropyridine derivatives in polar non-aqueous media

Acid dissociation, as well as cationic homoconjugation equilibria have been studied potentiometrically in systems involving four di-substituted 4-nitropyridines and conjugate cationic acids in the polar non-aqueous solvents - aprotic protophobic acetonitrile (AN) and propylene carbonate (PC), the amphiprotic methanol (MeOH), and in the aprotic protophilic dimethyl sulfoxide (DMSO). The influence of solvent effect on the obtained acidity constants has been discussed. The acidity constants (expressed as pK_a values) were compared with those previously determined in another polar protophobic aprotic solvent - acetone (AC), and obtained for the unsubstituted pyridine (Py). A comparison of the acid dissociation constants determined in all media studied has proved that the strength of the cationic acids increases on going from acetonitrile through propylene carbonate, acetone, and methanol to dimethyl sulfoxide. Furthermore, the values of acidity constants in the non-aqueous media have shown that in all the solvents studied they change according to the substituent effects. It has been also found that substituted 4-nitropyridine derivatives studied exhibit no tendency towards cationic homoconjugation in acetonitrile, propylene carbonate, and methanol and dimethyl sulfoxide. Moreover, it has been demonstrated that the acid dissociation constants determined by potentiometric titration method in all the solutions investigated correlate well with the calculated energy parameters of the protonation reactions in the gaseous phase.     

Solvent Effects on Tautomeric and Microscopic Protonation Constants of Glycine in Different Aqueous Solutions of Methanol and Ethanol

The acid-base equilibria of glycine have been studied in different aqueous solutions of methanol and ethanol (0?C45?% v/v) using a potentiometric method. In this study, the macro and micro protonation constants of the amino acid and its tautomeric constant have been determined at 25?°C and constant ionic strength (0.1 mol?dm^?3 NaClO₄). The protonation and the tautomeric constants of glycine in different binary mixtures were analyzed in terms of the Kamlet, Abboud and Taft (KAT) parameters. Single-parameter correlations of the constants versus ?? (hydrogen-bond donor acidity), ?? (hydrogen-bond acceptor basicity) and ?? ^? (dipolarity/polarizability) are poor in all solutions. Multi-parameter correlations show better results, but dual-parameter correlations represent significant improvements with regard to the single- and multi-parameter models. Linear correlation is observed when the experimental protonation constant values are plotted versus the calculated ones when the KAT parameters are considered. Finally, the results are discussed in terms of the effect of the solvent on protonation and tautomeric constants.     

Protonation of leucoemeraldine in the solid state and in solution

The protonation of leucoemeraldine in power form and in N-methylpyrrolidinone (NMP) solution by HCIO₄ and HBF₄ has been studied by x-ray photoelectron spectroscopy (XPS), infrared (IR), and ultraviolet (UV)-visible absorption spectroscopy. In powder form, less than 25% of the amine nitrogens can be protonated in the absence of oxygen. The effects of oxygen on the degree of protonation and the distribution of amine and imine units upon deprotonation of the salt are investigated. The degree of protonation in leuccemeraldine can be increased to about 50% with 3 M HCIO₄, similar to that achievable with emeraldine base in powder form. In NMP solution, leucoemeraldine is easily oxidized by dissolved oxygen. Protonation of both leucoemeraldine and emeraldine base in NMP solutions results in metastable species which gradually undergo deprotonation. The resulting products are affected by the O₂ content of the solutions. © 1993 John Wiley & Sons, Inc.     

Quantum chemical studies on the tautomerism of some potentially tautomeric aminoindazole derivatives

The aqueous phase AM1, PM3, and PM5 calculation data had indicated that when a potentially tautomeric amino group is placed at 3C position of the indazole ring the ring-chain tautomerism becomes feasible. However, when the amino group is placed at 4–7C of the indazole ring only the annular tautomerism was found to be feasible and no effect of amino group to provoke a ring chain tautomerism was observed. On the other hand amino form of 3 amino substituted indazole was found to be predominant over imino forms whereas for the 4–7 amino substituted indazoles imino forms were found to be predominant over amino forms. The attempt to apply soft–hard base and soft nucleophile–electrophile criteria to protonation and tautomerism phenomena was successful.     

Physical Image vs. Structure Relation. Part 3 [1]. Basic Properties and Protonation Mechanism of Some Tetraaza Macrocyclic Ligands

The protonation constants, log K, for 1,4,7,11-tetraazacyclotetradecane (isocyclam, 2), 1-(2-aminoethyl)-1,4,8,11-tetraazacyclotetradecane (scorpiand, 3), 5,12-dimethyl-1,4,8,11-tetraazacyclotetradecane (Me₂cyclam, 4) and 5,5,7,12,14,14-hexamethyl-1,4,8,11- tetraazacyclotetradecane (Me₆cyclam, 5) were determined pH-metrically. Attempts of correlation of the calculated enthalpy of protonation in the gas phase (AM1 method) with experimental values of the protonation constants for ligands 1, 2, 4–7 were done 1,4,8,11-tetraazacyclotetradecane, cyclam, 1; 1,4,7,10-tetraazacyclotetradecane, cyclen, 6; 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane, (N-Me)₄cyclam, 7. Extensive NMR pH-titrations, i.e., determination of pH vs. chemical shifts (¹H and/or ¹³C) plots, (_X = f(pH), allowed to suggest the most likely protonation schemes of all nitrogen atoms in the cyclic polyamines 1–3. The possibility of the formation-breaking of the intramolecular hydrogen bonds, as well as the change of conformation of these polybasic macrocycles during protonation-deprotonation steps, has been considered on the basis of the supplementary theoretical calculations (MMX/STO-3G study).     

Spectroscopy study of 5-amino-1,10-phenanthroline

Acidity constants for the 5-amino-1,10-phenanthroline (5-Aphen) were determined in aqueous media, using SQUAD and SUPERQUAD programs. Spectrophotometry and potentiometry data were fitted to the best model to enable correlation of the following acidity equilibria: 5-AphenH = 5-Aphen + H+ (-log K = 5.78 +/= 0.03) and 5-AphenH2 = 5-AphenH2 = 5-Aphen + 2H+ (-log K = 6.89 +/= 0.07). UV absorptivity coefficients obtained suggest that the first protonation takes place on the nitrogens of the heterocycle ring and the second protonation could take place on the amino group. As expected, the electrochemical evidence of the 5-Aphen species depends on the degree of protonation.     

Interaction of serum albumin with a sulphonated azo dye in acidic solution

The uptake of the sulphonated azo dye [1-(tetrazolylazo)-2-hydroxynaphthalene 3,6-disulphonic acid, or T-azo-R] by bovine serum albumin (BSA) in the pH range 1-4 was investigated by a spectrophotometric method, based on the fact that the absorption spectra of the free and bound dye are different. The effect of increasing concentration of sodium chloride and sodium perchlorate was considered, as well as the influence of the BSA on the protonation equilibria of the dye. The Scatchard model, which has been widely used previously to describe the interaction between small substances and proteins, was not helpful in the treatment of data obtained in the acidity range considered here. Instead a phase distribution model allowed a good quantitative treatment of the experimental findings. The distribution constant of the monoprotonated T-azo-R between aqueous solution and the albumin microphase was found to be log K(d(HL)/gamma'HL) = 6.3, while the biprotonated form does not bind to BSA. As a consequence, the protonation constant of T-azo-R is decreased in the presence of BSA, particularly at low salt concentrations in aqueous solution. An equation relating the observed protonation constant to the protonation constant of the dye in solution and to the ionic strength is proposed. It has been found that the effect of salts on the uptake of T-azo-R by BSA can be explained simply by considering the variation of the activity coefficients of the ionic species involved in aqueous solution.     

Dissolution of copper phthalocyanine and fabrication of its nano-structure film

The mono-protonated and di-protonated forms of copper phthalocyanine (CuPc) were obtained by increasing concentrations of trifluoroacetic acid (TFA) solution to a fixed concentration of CuPc solutions. UV-Vis spectrum shows that the Q bands of these two derivatives split and shift to the red, which means successive protonation happened and caused the two derivatives to lose their symmetry. After the protonation step, the solubility of protonated CuPc in organic solvent increased 60 times. The CuPc film was fabricated by the electrophoretic deposition (EPD) method from the protonated CuPc dissolved in nitromethane containing TFA. Scanning electron microscopy (SEM) showed that the deposited CuPc film on the indium tin oxide (ITO) substrate is composed of thread-like nanobelts with diameters between 100 nm and 200 nm. Furthermore, the CuPc film is in α phase with stacking direction (b-axis) parallel to the substrate, which was detected by X-ray diffraction.