Derivatives In Aqueous Solution Research Articles

Self-association of pyrimidine and some of its methyl derivatives in aqueous solution

The self-association of pyrimidine and some of its methyl derivatives (4- and 5-methylpyrimidine; 4-6-dimethylpyrimidine) was studied in aqueous solution, at different pH values, by UV spectroscopy. The variation in molar absorptivity with the concentration of these compounds was measured for the π → π * bands, at nearly 240 nm, and for the n → π * band, at nearly 270 nm, whenever this band was observable separately. Hyperchromic or hypochromic deviations from Beer's law with increasing concentration were detected. These effects were interpreted in terms of two processes of self-association: dimerization and polymerization. From the experimental data, self-association constants for dimerization ( K 2) and polymerization ( K n ) were calculated. The results obtained are discussed in relation to the structural features of each compound. In this work, the different behaviours of the π → π * and n → π * bands in the same compound have been observed for the first time. These behaviours can be interpreted, according to the theory of hypochromisim in polynucleotides, in terms of horizontal (colinear) interactions for the dimerization and vertical (stacking) interactions for the polymerization.

Self-association of pyrimidine and some of its methyl derivatives in aqueous solution

The self-association of pyrimidine and some of its methyl derivatives (4- and 5-methylpyrimidine; 4-6-dimethylpyrimidine) was studied in aqueous solution, at different pH values, by UV spectroscopy. The variation in molar absorptivity with the concentration of these compounds was measured for the π → π∗ bands, at nearly 240 nm, and for the n → π∗ band, at nearly 270 nm, whenever this band was observable separately. Hyperchromic or hypochromic deviations from Beer's law with increasing concentration were detected. These effects were interpreted in terms of two processes of self-association: dimerization and polymerization. From the experimental data, self-association constants for dimerization ( K 2) and polymerization ( K n ) were calculated. The results obtained are discussed in relation to the structural features of each compound. In this work, the different behaviours of the π → π∗ and n → π∗ bands in the same compound have been observed for the first time. These behaviours can be interpreted, according to the theory of hypochromism in polynucleotides, in terms of horizontal (colinear) interactions for the dimerization and vertical (stacking) interactions for the polymerization.

Comparative Study on the Conformation of Phalloidin, Viroisin, and Related Derivatives in Aqueous Solution

We investigated the conformations of toxic phalloidin and viroisin in aqueous solution using 500-MHz 1H-NMR spectroscopy in conjunction with molecular modeling. The conformations of two non-toxic phalloidin derivatives, secophalloidin and dethiophalloidin, were also correspondingly studied for comparison purposes. Results indicate that the non-toxic peptides have a multiple conformation, whereas the toxic peptides are comprised of a rigid molecule. It was found that the conformation of phalloidin partially resembles that of viroisin in the region of Cys3-Pro4-Ala5-Trp6, being different from that of the non-toxic peptides; thereby suggesting this region plays an important role leading to their toxicity.

Comparative Study on the Conformation of Phalloidin, Viroisin, and Related Derivatives in Aqueous Solution

Comparative Study on the Conformation of Phalloidin, Viroisin, and Related Derivatives in Aqueous Solution

Photogeneration of Highly Electrophilic Benzoylketene from Dibenzoyldiazomethane in Aqueous Solvents: Reaction with Amino Acids and DNA Cleavage

Photoirradiation of dibenzoyldiazomethane in the presence of amino acid derivatives in aqueous solutions efficiently produced the addition products through a reaction with photogenerated benzoylketene. Efficient DNA cleavage was observed with a dibenzoyldiazomethane derivative, possessing a cationic side chain under photoirradiation conditions.

Photogeneration of highly electrophilic benzoylketene from dibenzoyldiazomethane in aqueous solvents: Reaction with amino acids and DNA cleavage

Photoirradiation of dibenzoyldiazomethane in the presence of amino acid derivatives in aqueous solutions efficiently produced the addition products through a reaction with photogenerated benzoylketene. Efficient DNA cleavage was observed with a dibenzoyldiazomethane derivative, possessing a cationic side chain under photoirradiation conditions.

Effect of methylation on the pyrimidine-pyrimidine stacking interaction studied by 1H NMR chemical shift

Mutually induced proton chemical shift changes were measured for the mixed solutions of pyrimidine and its methylated forms in deuterium oxide at 35°C. The chemical shift vs. concentration profiles were analyzed using a three-state decomposition model based on competitive self- and hetero-association dimer equilibria. The equilibrium constants show an increasing association tendency within the series pyrimidine-5-methyl-pyrimidine (0.23 ± 0.02 M −1) < pyrimidine-4,6-dimethyl-pyrimidine (0.32 ± 0.04 M −1) < 5-methyl-pyrimidine-4,6-dimethyl-pyrimidine (0.51 ± 0.04 M −1). The upfield dimer shifts suggest an offset stacked geometry for the structure of associations between the parent molecule of the pyrimidine nucleobases and its methylated derivatives in aqueous solution.

Self-association of pyridine and some of its derivatives in aqueous solution: influence of alkyl substituents

Abstract The self-association of pyridine and some of its alkyl derivatives (2-, 3- and 4-picoline, 2,4- and 2,6-lutidine, 4-tert-butyl- and 2,6-di-tert-butylpyridine) was studied in aqueous solution, at different pH values, by UV spectroscopy. The variation in molar absorptivity with concentration was measured not only for the main maximum, but also for the different component bands of the adsorption band in the mid-UV region (above 200 nm) of these compounds. From the experimental curves of hypochromic effects, self-association constants for dimerization (K2) and polymerization (Kn) were calculated. The results obtained are discussed in detail with relation to the position and nature of alkyl substituents on the pyridine ring. The most relevant result is the influence of alkyl substituents on self-association, particularly the special role of the methyl substituents in ortho positions with respect to the nitrogen atom in 2-picoline, 2,4- and 2,6-lutidine. In 2-picoline and 2,6-lutidine, polymerization can be studied separately from dimerization by measuring the band at longest wavelength, which suggests a possible relationship between the mechanism of formation of polymers and the π* ← n transitions which give rise to these bands.

N4-(Dialkylamino)methylene Derivatives of 2′-Deoxycytidine and Arabinocytidine: Physicochemical Studies for Potential Prodrug Applications

The synthesis and physicochemical parameters of a series ofN4-(N,N-dialkyl)formamidine derivatives of 2′-deoxycytidine (dCyd,1) and arabinocytidine (ara-C,2), as prodrug prototypes, are described. The lipophilicity of the formamidine derivatives compared to that of the parent nucleosides increased 1.26- to 145-fold. The corresponding half-lives of the derivatives in aqueous solution at pH 7.4 and 37 °C ranged from 3.7 to 52 h. The analogues most stable to hydrolysis in both series (3and4) were the diisopropyl derivatives (3dand4d). The substitution effects of the sugar OH groups at the 2′- and 3′-positions on the corresponding partition coefficients gave π-values of −0.16 and −0.55, respectively. These values are significantly more positive than those generally associated with aliphatic hydroxy substituents indicating that sugar OH groups of nucleosides have a decreased tendency to associate with the aqueous phase. Thein vitrogrowth inhibitory activities of theara-C derivatives (4) against murine lymphocytic leukemia L1210 cells indicate that prodrug to drug conversion readily occurs. The results confirm our previous findings about the versatility of the formamidine modification of nucleosides bearing exocyclic amino groups. The data facilitate optimization of lipophilicities and hydrolytic stabilities and thus contribute to the design and further development of the formamidine type of prodrug derivatives.

Comparative study on Inclusion compounds of 4-Biphenylacetic acid with β-Cyclodextrin, Hydroxypropylated-β-Cyclodextrins, and methylated-β-Cyclodextrins

The inclusion behavior of Hydroxypropyl-β-Cyclodextrin (HP-β-Cyd) and of methylated-β-Cyclodextrins, heptakis-(2,6-di-O-methyl)-β-Cyclodextrin (DM-β-Cyd) and heptakis-(2,3,6-tri-O-methyl)-β-Cyclodextrin (TM-β-Cyd), in solution and solid state was compared with that of natural β-Cyclodextrin (β-Cyd) using an anti-inflammatory drug, 4-biphenylacetic acid (BPAA), as a guest molecule. The solubility of BPAA with β-Cyd and β-Cyd derivatives in aqueous solution were determined. Stability constants were calculated by phase solubility method at various pH values and temperatures. The formation of inclusion complexes with β-Cyd and β-Cyd derivatives in the solid slate were confirmed by infrared spectroscopy, differential scanning calorimetry and X-Ray diffractometry, and in the liquid phase by ultraviolet spectroscopy, circular dichroism and NMR studies. Dissolution rate and “in vitro” release of BPAA from complexes were examined. The results obtained suggest that DM-β-Cyd is more effective than other β-Cyclodextrins in improving the pharmaceutical properties of BPAA.

1H and 13C NMR studies of aminoglycoside antibiotics

Abstract1H NMR spectroscopy was used to determine the conformations of the aminoglycoside antibiotic N‐demethylclindamycin and two of its cyclic derivatives. The conformational features of these systems were determined by consideration of vicinal coupling constants and, in some cases, nuclear Overhauser enhancement (NOE) effects. 1H and 13C chemical shifts are reported and compared with previous results for the related antibiotic lincomycin. The stability of the two cyclized derivatives in aqueous solution was examined. Both cyclizations involved formation of a 4‐imidazolidinone ring. It was found that the ring system based on cyclization with formaldehyde was stable in aqueous solution, whereas that based on benzaldehyde was not.

High-frequency dielectric relaxation measurements of side-chain dynamics of branched chitosan derivatives in aqueous solutions

The linear chain of polysaccharide chitosan has been derivatized by attaching different molecules to the 2-amino function of the backbone, namely lactose and ketoglutaric acid, therefore yielding branched comblike polymers. The dielectric behavior of aqueous solutions of these derivatives has been investigated in the frequency range from 1 MHz to 1 GHz, where pronounced dielectric dispersions occur. The deconvolution of both the permittivity and the dielectric loss spectrum into more than one dielectric mechanism shows that the high-frequency dielectric dispersion can be attributed to side-chain motions. The influence of pH and different species of counterions is investigated

Sorption equilibria of pyridine derivatives in aqueous solution on porous resins and ion exchange resins.

Studies have been made of the sorption equilibria of pyridine, picoline and lutidine in aqueous solution on ion-exchange and porous resins. The sorption behaviors of these pyridines on strong acid ion-exchange resin can be expressed by the Langmuir isotherms, and those on both weak acid ion-exchange and porous resins by the Freundlich isotherms. The sorption mechanisms followed either a neutralization reaction with the H-form ion-exchange resins, or a hydrophobic interaction with the porous resins. Methanol content of the aqueous solution as well as solution pH was found to have a significant effect on the sorption of pyridines.Furthermore, the separations of these pyridines from each other were examined for three binary solute solutions in a batch mode. The pyridines were sorbed preferentially on the resins in the following sequence:pyridine where the selectivity increased as follows:strong acid ion-exchange resin

Use of nonradiative energy transfer to explore interpolymer and polymer-solute interactions in aqueous solutions of poly(N-isopropylacrylamide)

N-Isopropylacrylamide (NIPAAM) was copolymerized with small quantities of 9-fluorenylmethyl acrylate to yield labeled poly(N-isopropylacrylamide) (PNIPAAM) for use in nonradiative energy transfer (NRET) experiments with various pyrene derivatives in aqueous solution. Microcalorimetry and cloud point measurements of the lower critical solution temperatures (LCST) of these copolymers showed very slight depressions in the LCST as compared to that of the homopolymer. NRET investigations showed no energy transfer from fluorene-labeled PNIPAAM to free pyrene or to PNIPAAM-bound pyrene in mixed aqueous solutions at 24.5 C in contrast to literature reports of similar work done with (hydroxypropyl)-cellulose. NRET was observed between fluorene-labeled PNIPAAM and amphiphiles with pyrene terminally bound to their hydrocarbon tails. NRET was much more efficient for a quaternary ammonium amphiphile than for a zwitterionic sulfobetaine-based surfactant.

Voltammetric behavior of a ferrocene derivative: A comparison using surface-confined and diffusion-controlled species

Description of cyclic voltammetry and an experiment that examines the voltammetric behavior of a ferrocene derivative in aqueous solution (diffusion-controlled) and inside an anionic polyelectrolyte film (diffusion-controlled).

Photosolvolysis of 9-fluorenol derivatives in aqueous solution—exploratory studies of reactivity of photogenerated 9-fluorenyl cations

The photosolvolysis of several 9-fluorenol derivatives ( –7) substituted at the 9-position has been studied in aqueous CH 3CN and CH 3OH solutions. The purpose of the study was to examine structure reactivity for photodehydroxylation of 9-fluorenol derivatives, giving rise to 9-fluorenyl cations, and subsequent chemistry of these photogenerated cations, which are formally anti-aromatic in the ground state. Derivatives 4–7 all photodehydroxylated efficiently, as measured by quantum yields for methyl ether formation. The photogenerated 9-fluorenyl cation from compound 4 also undergoes efficient E1 reaction, to give alkene 10. However, the corresponding pathway for compound 6 was inefficient due to the inabililty of the adjacent proton to line up in a periplanar arrangement with the empty p z orbital, as indicated by molecular mechanics (MMX) calculations. Photolysis of 9-vinyl-9-fluorenol (compound 5) in aqueous CH 3CN gave 9-methylenefluorene derivative 20 via a simple isomerization, showing that the initially photogenerated 9-fluorenyl cation is significantly delocalized.

Substituent and pH effects on self-association of pyridine derivatives in aqueous solution. An ultraviolet study

Self-association of pyridine, 2-picoline, pyridine monocarboxylic acids, methyl nicotinate, and dipicolinic acid, has been studied in aqueous solution by ultraviolet spectroscopy, as an extension of previous work. The spectra of these compounds, under suitable conditions of pH, show an hypochromic effect with increasing concentration over the range from 10 −6 to 10 −1 M, which is interpreted in terms of self-association. Association constants are calculated from dimerization and polymerization models. The results are discussed in terms of the nature of substituents and the protonation states, and show that interactions in dilute solutions are important in the self-association processes of these compounds in aqueous solution.

Prototropic equilibria of 2-pyridylbenzimidazoles in aqueous solution

In this paper we report the acid–base behaviour of 2-(n′-pyridyl)benzimidazoles (n′ = 2,3,4) and some methyl derivatives in aqueous solution over a wide range of acidity, involving interesting features with respect to competition in protonation between the benzimidazole N3 and the pyridyl N, with the existence of the corresponding two monocations in equilibrium in the case of n′ = 4. The influence of pH on the electronic absorption spectra of all compounds has been studied in order to identify the ground-state species present as a function of acidity and to obtain the acidity constants of the various prototropic equilibria occurring in the wide range of acidity studied. Keywords: 2-pyridylbenzimidazoles, prototropic equilibria, protonation, acidity constants.

Optically active mono and bis(1,1′-binaphthyl)-cyclophanes: Large differences in the complexation of naproxen derivatives in aqueous solution

Four new optically active cyclophanes with apolar cavities shaped by the major grooves of the 2,2′, 6,6′- nd 2,2′, 7,7′-tetraoxa-1,1′-binaphthyl units were prepared for the inclusion complexation of naproxen derivatives in aqueous solution. Macrocycles formed by one diphenylmethane and one binaphthyl spacer give stronger binding and, unexpectedly, a higher degree of chiral recognition than cyclophanes formed by two bridged binaphthyl derivatives.

Prodrugs of peptides. 12. Bioreversible derivatization of thyrotropin-releasing hormone (TRH) by N-phthalidylation of its imidazole moiety

N-Phthalidylation of the imidazole group in TRH (pGlu-His-Pro-NH 2) was found to be a promising approach to obtain prodrug forms of this tripeptide, with the aim of protecting it against rapid enzymatic inactivation in the systemic circulation. The N-phthalidyl derivative of TRH was shown to be resistant to cleavage by the TRH-specific pyroglutamyl aminopeptidase serum enzyme but is, on the other hand, readily bioreversible by virtue of spontaneous or plasma esterase-catalyzed opening of the phthalidyl lactone ring to yield TRH in a two-step process. The pH-rate profile for the degradation of the derivative in aqueous solution was determined and accounted for in terms of specific acid- and base-catalyzed reactions in addition to a spontaneous hydrolysis. Like previously studied N-alkoxycarbonyl derivatives the phthalidyl derivative did not protect TRH against cleavage by unspecific pyroglutamyl aminopeptidase (PAPase I) or intestinal prolyl endopeptidase.