Ligand effects in the substitution chemistry of cis-bis(piperidine)tetracarbonylmolybdenum(O). A molybdenum-95 NMR study

Molybdenum-95 NMR chemical shifts are reported for a series of Mo(O) compounds of the type Mo(CO)₄(pip)_2−nL_n(n = 1,2; L = substituted pyridine ligands). The σ(⁹⁵Mo) values correlate well with the pK_a values for the substituted pyridines; for the n = 1 series, σ (⁹⁵Mo) ranges from − 1053 ppm (pK_a = 1.86 for 4-CN) to − 1120 ppm (pK_a = 9.61 for 4-NMe₂). The effects of solvent polarity and some in situ reactivity studies are described and the nature of the MoL bond compared to that with piperidine and some other ligands is discussed.     

New description of the substituent effect on electronic spectra by means of substituent constants—VI. Utraviolet spectra of 4-substituted pyridine N-oxides and blue shifted iodine bands of their EDA complexes with iodine

Electronic spectra of 4-substituted pyridine N-oxides and their EDA complexes with iodine were studied. The substituent effect on the near u.v.¹A₁ intramolecular CT bands of the N-oxides and on the blue shifted iodine bands caused by CT complex formation are discussed in terms of a general equation, theoretically derived in order to describe the substituent effect on electronic spectra by means of substituent constants. The results are quite successful and supported by semi-empirical SCFMO-CI calculations. Based on the results mentioned above, the character of n-σ type N-oxide—iodine CT complexes is also examined. The complex formation constants (log K) and pK_a values of the N-oxides correlate especially well, indicating that the CT interaction mechanism cannot be neglected in proton addition reactions such as hydrogen bonding and pK_a values.     

Ionisation of some flavanols and dihydroflavonols

Ionisation constants of catechin (1), robinetinidol (2), leuco-fisetinidin (3), fustin (4), dihydrorobinetin (5), dihydroquercetin (6) and a series of polyphenols are reported. The pK_a values of these flavonoids are shown to fit the linear relationships between pK_a, and substituent σ constant for a series of related phenols.     

Polynuclear tetrazole-containing amino acid analogs

New analogs of (D,L)-phenylalanine containing tetrazole rings were synthesized. The acidity constants of (D, L)-phenylalanine and (D,L)-tryptophane derivatives containing a tetrazole ring with no substituent on N¹ (pK _a = 3.0–3.1) and of the corresponding carboxylic acids (pK _a = 2.9–3.3) in aqueous methanol were determined by potentiometric titration.Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 10, 2004, pp. 1576–1579.Original Russian Text Copyright © 2004 by Morozova, Esikov, Zubarev, Malin, Ostrovskii.     

Reaction of α,β-unsaturated ketones with guanidine. Substituent effects on the protonation constants of 2-amino-4,6-diarylpyrimidines

1,3-Diaryl-2-propen-1-ones, I, reacted with guanidine hydrochloride (II) in the presence of 3 moles of sodium hydroxide to give the corresponding 2-amino-4,6-diarylpyrimidines, III. The structure and configuration of the products are based on chemical and spectroscopic evidence. The protonation constants of these compounds (series A and series B) have been determined in 50 volume percent ethanol-water medium. Excellent linear correlations are obtained when pK_a values of the two series of 2-amino-4,6-diarylpyrimidines, IIIa-j and IIIk-r, are plotted against the substituent constant, ^σx, and the polar substituent constant, ^σ* xC₆H₄, for substituted phenyl groups. The pK_a values have also been correlated with the extended Hammett equation. The correlation follows the equations: Series A; pK_a = 3.273 - 0.820σI,X - 0.662σR,X Series B; pK_a = 3.169 - 0.424σI,X - 0.137σR,X     

Visible absorption spectral measurements of the formation of the cobalt porphyrin dioxygen complex using a high-pressure cell ag

The 1:1 complex formation between dioxygen and the meso-tetraphenylporphinatocobalt(II)pyridine complex in toluene was followed spectrophotometrically using a high-pressure cell. The values of the equilibrium constant K_p obtained are 0.0278, 0.0513, 0.0840, 0.157 and 0.278 atm⁻¹ at −30, −36, −42, −48 and −54dgC, respectively. The thermodynamic data are ΔH^θ = −10.1±0.6 kcal mol⁻¹ and gDS^θ = −49±3 eu at a standard pressure of 1 atm.     

Base-Modified Nucleosides Related to 2-Chloro-2′-deoxyadenosine

Derivatives of 2-chloro-2′-deoxyadenosine ( 1a ) containing secondary 6-NH₂ groups ( 5a-c ) or a 8-Br substituent ( 9 ) were synthesized. They were tested together with ring-modified congeners containing a pyrrolo[2,3-b]pyridine, pyrrolo[3,2-c]pyridine, or pyrazolo[3,4-d]pyrimidine ring system as inhibitors of various leukemic cell lines. Only the 8-Br derivatives 9 showed inhibitory activity, whereas the base-modified congeners were not active. Compound 1a was protonated at a pK_a = 1.4 (2′-deoxyadenosine at pK_a = 3.8). Protonation occurred at N(7) and not at N(1) as observed for dA.     

Substituent effects in 13C NMR spectroscopy: Methyl,ethyl, 2-propyl and 2-methyl-2-propyl carboxylates

The ¹³C chemical shifts of the 28 carboxylic esters have been determined by high-resolution NMR spectroscopy with the aid of proton decoupling. A linear relationship is shown to exist between the ¹³C chemical shifts of the carbinyl carbon (C-1) of the esters and the pK_a values of the acids from which they are derived. This is a consequent of the polar character of the

bond. Similarly, if the carboxyl group is kept constant, but the alcoholic part of the ester is varied from primary to secondary and tertiary alcohols, the esterification effect on C-1 can be correlated with the increasing stability of the +δ charge on the carbinyl carbon. The smallest esterification effect at C-1 (1.3 ppm, relative to the parent alcohol) is observed for methyl pivalate (pK_a 5.03 for the parent acid), and the highest effect (17.7 ppm) for 2-methyl-2-propyl trichloroacetate (pK_a 0.70). In contrast, the C-2 esterification effect has been found to be essentially constant (?3.8±0.7 ppm), which is in agreement only with a conformation of the ester group in which the carbinyl carbon is cis with respect to the CO group.     

Nucleophilicity of N-propargylanilines in the coordination to zinc tetraphenylporphyrin in chloroform

Thermodynamic parameters (ΔG ⁰ and ΔS ⁰) of the isoenthalpic (except for 4-halo derivatives) coordination of (tetraphenylporphyrinato)zinc(II) with anilines in chloroform at 273–313 K linearly correlate with the shift of their electronic absorption maxima in the reaction with anilines, as well as with the logarithms of the stability constants of the complexes, pK _a values of the ligands in water, and substituent constants σ⁺. The 2: 1 complex of (tetraphenylporphyrinato)zinc(II) with p-phenylenediamine was characterized by the X-ray diffraction data     

The modified hartree-fock self-consistent field equation

The electron density at the pyridine nitrogen atom and the π-electron density of the pyridine ring were calculated by the CNDO /2-MO method assuming standard bond lengths and angles. The indices were found to correlate with the pK_a values of pyridine derivatives and with the electronic substituent constants of the Hammett type. The correlations were best for four-substituted pyridines, making the routine CNDO /2-MO calculations useful for studies of quantitative relations between structure and biological activity of the compounds.     

Study on various fluorescein derivatives as pH sensors

Various fluorescein derivatives were examined as fluorescent pH sensors. Fluorescein derivatives bearing benzylic amine moieties displayed opposite fluorescent changes compared to those of simple fluorescein derivatives upon pH changes. Photo-induced electron transfer (PET) mechanism controls the fluorescent changes of these derivatives. In this Letter, modulations of pK_a values were successfully demonstrated through variations of substituent groups.     

Hydrogen bonding and the protonation site in 3-methyl-4-pyrimidone

The interaction between 3-methyl-4-pyrimidone and phenol derivatives or HBr has been studied by IR spectrometry in solution and in the solid state. For pK_a values ranging from 10.3 to 4.5, normal OH··· OC hydrogen bonds are formed. With stronger acids (PK_a = 0.4 to ?6) protonation occurs at the N(1) nitrogen atom of the ring. For phenols of intermediate pK_a values (3.5), there is no preferred site of interaction, both OH···OC and NH⁺···O^? bonds being formed in solution.     

Acid dissociation constants of uridine-5′-diphosphate compounds determined by phosphorus nuclear magnetic resonance spectroscopy and internal pH referencing

The acid dissociation constant (pK_a) of small, biological molecules is an important physical property used for investigating enzyme mechanisms and inhibitor design. For phosphorus-containing molecules, the ³¹P nuclear magnetic resonance (NMR) chemical shift is sensitive to the local chemical environment, particularly to changes in the electronic state of the molecule. Taking advantage of this property, we present a ³¹P NMR approach that uses inorganic phosphate buffer as an internal pH reference to determine the pK_a values of the imide and second diphosphate of uridine-5′-diphosphate compounds, including the first reported values for UDP-GlcNAc and UDP-S-GlcNAc. New methods for using inorganic phosphate buffer as an internal pH reference, involving mathematical correction factors and careful control of the chemical shift reference sample, are illustrated. A comparison of the newly determined imide and diphosphate pK_a values of UDP, UDP-GlcNAc, and UDP-S-GlcNAc with other nucleotide phosphate and thio-analogs reveals the significance of the monosaccharide and sulfur position on the pK_a values.     

Infrared spectrometric study of the interaction between 2-dimethylamino-3,3-dimethyl-1 azirine and some phenol derivatives

The H-bonded complexes between 2-dimethylamino-3,3-dimethyl-1-azirine (TMAAZ) and some phenol derivatives have been studied by IR spectrometry in carbon tetrachloride. The equilibrium constants at 300, 315 and 328 K and the ? ΔH°, ? Δν_OH and Δν_CN values have been determined. The comparison with previously studied OH … N complexes shows that TMAAZ forms stronger complexes than would be expected from the pK_a value. These facts are discussed in terms of steric, hybridization, solvation and charge transfer effects. From a pK_a of 8, the IR spectrum shows the appearance of ion pairs N⁺-H …^?O. A predominance of protonated species can be calculated for a pK_a of 6. This can explain why 1,2-ring cleavage whose first step is probably the formation of an azirinium cation, occurs for acids characterized by pK_a values lower than 5 but not for enolizable ketones having pK_a values higher than 9.     

What are the pKa values of organophosphorus compounds?

A first-principle theoretical protocol was developed, which could successfully predict the pK_a values of a number of amines and thiols in DMSO with a precision of about 1.1 pK_a unit. Using this protocol we calculated the pK_a values of diverse types of organophosphorus compounds in DMSO. The accuracy of these predicted values was estimated to be about 1.1 pK_a because phosphorus is in the same group as nitrogen and in the same period as sulfur. The theoretical predictions were also consistent with all the available experimental data. Thus, a scale of reliable pK_a values was constructed for the first time for organophosphorus. These pK_a values would be helpful to synthetic chemists who need to design the experimental conditions for handling deprotonated organophosphorus. On the basis of these pK_a values we also studied, for the first time, some interesting topics such as the substituent effects on the pK_a values of various types of organophosphorus, and the differences between the pK_a values of organophosphorus and organic amines.     

Analytical properties of the amidoxime group: X. Potentiometric and thermometric behaviour of 3,5-dimethyl-4-isoxazolylacetamidoxime

Dissociation equilibria of 3,5-dimethyl-4-isoxazolyl-acetamidoxime (DMIAA) were studied by means of potentiometric and thermometric techniques in ethanol-water media.Refined pK values (pK₁ = 4.05; pK₂ = 11.34) and neutralization enthalpy (ΔH₁ = −7.57 kcal mol⁻¹) were obtained using several computer programs (GRAN, MINIPOT, MINIQUAD and MINITERM).Titration errors and thermodynamic parameters of DMIAA are compared to the corresponding values obtained for other amidoximes studied in previous papers.     

Determination of acidity constants,ionic mobilities,and hydrodynamic radii of carborane-based inhibitors of carbonic anhydrases by capillary electrophoresis

Capillary electrophoresis (CE) has been applied for determination of the thermodynamic acidity constants (pK_a) of the sulfamidoalkyl and sulfonamidoalkyl groups, the actual and limiting ionic mobilities and hydrodynamic radii of important compounds, eight carborane-based inhibitors of carbonic anhydrases, which are potential new anticancer drugs. Two types of carboranes were investigated, (i) icosahedral cobalt bis(dicarbollide)(1-) ion with sulfamidoalkyl moieties, and (ii) 7,8-nido-dicarbaundecaborate with sulfonamidoalkyl side chains. First, the mixed acidity constants, pK_a^mix, of the sulfamidoalkyl and sulfonamidoalkyl groups of the above carboranes and their actual ionic mobilities were determined by nonlinear regression analysis of the pH dependences of their effective electrophoretic mobility measured by capillary electrophoresis in the pH range 8.00−12.25, at constant ionic strength (25 mM), and constant temperature (25°C). Second, the pK_a^mix were recalculated to the thermodynamic pK_as using the Debye–Hückel theory. The sulfamidoalkyl and sulfonamidoalkyl groups were found to be very weakly acidic with the pK_as in the range 10.78−11.45 depending on the type of carborane cluster and on the position and length of the alkyl chain on the carborane scaffold. These pK_as were in a good agreement with the pK_as (10.67−11.27) obtained by new program AnglerFish (freeware at https://echmet.natur.cuni.cz ), which provides thermodynamic pK_as and limiting ionic mobilities directly from the raw CE data. The absolute values of the limiting ionic mobilities of univalent and divalent carborane anions were in the range 18.3−27.8 TU (Tiselius unit, 1 × 10⁻⁹ m²/Vs), and 36.4−45.9 TU, respectively. The Stokes hydrodynamic radii of univalent and divalent carborane anions varied in the range 0.34−0.52 and 0.42−0.52 nm, respectively.     

Acid-base chemistry of omeprazole in aqueous solutions

Omeprazole is a potent anti-acid drug. Its absorption and mode of action are closely related to its prototropic behavior. In the present study, omeprazole samples from different sources and in different forms were studied spectrophotometrically to obtain pK_a values. In the neutral to alkaline pH region, two consistent pK_a values of 7.1 and 14.7 were obtained from various samples. The assignment of these pK_a values was realized by comparison with the prototropic properties of N(1)-methylated omeprazole substituted on the nitrogen at the 1-position of the benzimidazole ring, which was found to have a pK_a of 7.5. The omeprazole pK_a of 14.7 is assigned to the dissociation of the hydrogen from the 1-position of the benzimidazole ring and the pK_a of 7.1 is assigned to the dissociation from the protonated pyridine nitrogen of omeprazole. The results presented are at variance with those of earlier work.     

Determination of dissociation constants of sparingly soluble phenothiazine derivatives by second-derivative spectrophotometry

The dissociation constants (pK_a) for sparingly soluble phenothiazines (promazine, chlorpromazine, trifluoropromazine) in water were measured by second-derivative spectrophotometry. The intense background signals in the absorption spectra due to the turbidity caused by the precipitation of insoluble free base of the phenothiazine derivatives were eliminated in the second-derivative spectra, and the solubilities of the phenothiazine derivatives could be easily determined from the peak-to-trough lengths (D values) of the second-derivative signals. The pK_a values were calculated from the pH dependence of the D values. The pK_a values obtained agreed well with reported values and the standard deviations for 6–10 determinations were ? 0.02. The solubilities of the free bases of the phenothiazines were also determined.     

Quantitative relations holding in coordination of (Tetraphenylporphyrinato)zinc(II) and nucleophilic substitution with anilines

Thermodynamic parameters (??G°, ??S°) of quasi-isoenthalpic coordination of (tetraphenylporphyrinato) zinc(II) with anilines (except for 4-halo derivatives) in chloroform at 273?C313 K in the absence of steric factors are linearly related to shifts of their absorption bands in the electronic spectra in reactions with anilines, as well as with logarithms of the stability constants of the complexes, pK _a values of the ligands in water, and Hammett substituent constants ??⁺. Linear relations were also found between thermodynamic and kinetic parameters of some nucleophilic substitution reactions and complex formation of (tetraphenylporphyrinato) zinc(II) with anilines.