Félix Arranz

Poly (vinyl alcohol) functionalized by monosuccinate groups. Coupling of bioactive amino compounds

Abstract Poly (vinyl alcohol) (PVAL) partially functionalized with monosuccinate groups was obtained by reaction of PVAL with succinic anhydride using triethylamine as catalyst and N-Methyl-2-pyrrolidone as solvent. The structure of the resulting polymers was determined by 1 H and 13 C nuclear magnetic resonance (n.m.r.) spectroscopy. The influence of the type of catalyst, solvent composition and temperature was evaluated. The activation energy was found to be 31.8 kJ/mol. 13 C n.m.r. spectroscopy was used for the determination of the sequence distribution of partially modified PVAL [considered as a vinyl alcohol (VAL)-vinyl succinate (VSU) copolymer]. The results obtained show that VSU units have a random distribution with a slight alternating tendency in the copolymer. High degrees of modification were obtained in the coupling of model bioactive amino compounds (benzocaine, phenethylamine and 2-amino-2-deoxy-D-glucose (glucosamine)) to monosuccinylated PVAL activated with ethyl chloroformate. Interaction experiments between glucosamine-carrying PVAL (PVAL-G) and Concanavalin A (Con A) in a phosphate buffer (pH 7.2) at room temperature showed that PVAL-G interacts with Con A.

13C nuclear magnetic resonance spectral study on the distribution of substituents in relation to the preparation method of partially acetylated dextrans

13C nuclear magnetic resonance (n.m.r.) spectra of partially modified dextrans with acetyl groups prepared by reaction with acetyl chloride or acetic anhydride in the homogeneous phase were analysed at 75.4 MHz. It was found that the distribution of substituents in the anhydroglucose units of these partially acetylated dextrans can be estimated from their ring carbon spectra. The results showed that for acetylated dextrans prepared by reaction with acetyl chloride, the reactivity of individual secondary hydroxyl groups decreases in the order C-2 > C-4 > C-3. For those modified dextrans prepared with acetic anhydride, the ease of acetylation was C-2⋍C-3 >C-4. The results were explained by considering the formation of intramolecular hydrogen bonds as well as by steric considerations.

Functionalization of dextran with chloroacetate groups: immobilization of bioactive carboxylic acids

Abstract Dextrans partially functionalized with chloroacetate groups were obtained by reaction of dextran with chloroacetyl chloride using pyridine as catalyst and the dimethylformamide/LiCl system as solvent. The structure of the resulting polymers was determined by means of infra-red, 1 H and 13 C nuclear magnetic resonance (n.m.r.) spectroscopy. 13 C n.m.r. spectra at 75.4 MHz of partially modified dextran with chloroacetate groups were studied in order to evaluate the selectivity of the reaction of dextran with chloroacetyl chloride in the homogeneous phase. Analysis of the spectra of ring carbons in the anhydroglucose units shows that the reactivity of the individual hydroxyl groups decreases in the order C2 > C3 > C4. The coupling of model bioactive carboxylic acids (α-naphthylacetic and 6-methoxy-α-2-naphthaleneacetic (naproxen)) to dextran functionalized with chloroacetate groups was carried out by reaction with their potassium salts or directly in the presence of 1,8-diazabicyclo[5.4.0]-7-undecene. High degrees of modification were obtained by both methods. However, the esterification reaction is somewhat more efficient in the case of the potassium salts.

Preparation of dextran-bioactive compound adducts by the direct esterification of dextran with bioactive carboxylic acids

Abstract The direct esterification reaction of dextran with α-naphthylacetic acid (a model bioactive carboxylic acid) is studied in homogeneous phase using pyridine-sulfonyl chloride as catalyst. The structure of the resulting adducts was determined by means of infra-red, 1H nuclear magnetic resonance (n.m.r.) and 13C n.m.r. spectroscopy. The influence of the pyridine concentration, the type of the sulfonyl chloride as well as the temperature was evaluated. Direct esterification reaction was also performed with other bioactive carboxylic acids, such as naproxen and nicotinic acid. 13C n.m.r. spectra at 75.4 MHz of partially modified dextran with α-naphthylacetate groups were studied in order to evaluate the selectivity of the reaction between dextran and α-naphthylacetic acid. Analysis of the spectra of ring carbons in the anhydroglucose units shows that the reactivity of the individual hydroxyl groups decreases in the order C2 > C4 > C3. On the basis of these results a probable mechanism for the reaction is suggested.

Relative reactivities of amylose hydroxyl groups in the reaction with diketene

Abstract 13 C nuclear magnetic resonance (n.m.r.) spectra at 75.4 MHz of partially modified amylose with β-keto ester groups (degree of substitution ( DS ) ranging from 0.52 to 2.42) were studied in order to evaluate the selectivity of the reaction of amylose with diketene in the homogeneous phase. Analysis of the spectra of ring carbons in the anhydroglucose units shows that the reactivity of individual hydroxyl groups decreases in the order C-6>C-3>C-2 for DS values up to ∼1.8. For higher DS values a negative deviation is observed for the hydroxyl group at C-6 and a positive deviation for the hydroxyl groups at C-2 and C-3. The DS values determined by 13 C n.m.r. spectra are in good agreement with those found by chemical analysis.

Synthesis of amidoxime-containing modified dextran

Abstract Dextrans partially modified with cyanoethyl groups were obtained by reaction of dextran with acrylonitrile in alkaline medium. The structure of the resulting polymers was determined by means of infra-red spectroscopy and 1 H and 13 C nuclear magnetic resonance (n.m.r.) spectroscopy. The influence of solvent composition, temperature and acrylonitrile concentration as well as the type and concentration of catalyst was evaluated. 13 C n.m.r. spectra at 75.4 MHz of partially modified dextran with cyanoethyl groups were studied in order to evaluate the selectivity of the reaction of dextran with acrylonitrile in the homogeneous phase. Analysis of the spectra of ring carbons in the anhydroglucose units shows that the reactivity of the individual hydroxyl groups decreases in the order C2 > C4 > C3. Nitrile groups in cyanoethylated dextran were converted to amidoxime groups by reaction with hydroxylamine. The activation energy was found to be 42.7 kJ mol −1 . Preliminary experiments showed the Cu 2+ complex formation ability of amidoximated dextran.

Vinyl alcohol-vinyl propionate copolymers: sequence distribution and glass transition

Abstract 13C nuclear magnetic resonance (n.m.r.) spectroscopy was used for the determination of the sequence distribution in vinyl alcohol-vinyl propionate (VAL-VP) copolymers prepared by two different methods: by partial alkaline hydrolysis of poly(vinyl propionate) and by partial esterification of poly(vinyl alcohol). The 13C n.m.r. spectra of the methylene carbons in the main chain show three split peaks, whose intensities change with copolymer composition. These peaks can be assigned to the three dyad sequences. The results obtained show that vinyl propionate units have an alternating tendency in VAL-VP copolymers prepared by esterification and a block distribution in VAL-VP copolymers prepared by hydrolysis. The Tg values of VAL-VP copolymers prepared by the two different methods are influenced by both the overall copolymer composition and the monomer sequence distribution.

Heterogeneous hydrolytic behaviour of dextran-α-naphthylacetic and dextran-naproxen adducts

Abstract This work deals with the bioactive agent release from dextran-α-naphthylacetic and dextran-naproxen adducts, in which the bioactive agent is linked to the dextran carrier through a spacer. Water absorption characteristics of these adducts have been studied. The hydrolysis in the heterogeneous phase showed autocatalytic effects and the release of the active compound is dependent upon the hydrophilic character of the adduct as well as the pH value of the medium.

Kinetic study of the hydrolysis of vinyl alcohol-vinyl n-alkyl carbonate copolymers

A kinetic study of the hydrolysis of vinyl alcohol-vinyl n-alkyl carbonate copolymers has been made as a function of the base or acid concentration, the temperature, and the structure of the carbonate units. The homogeneous hydrolysis in alkaline medium was found to be first order with respect to both the hydroxyl ion and the carbonate; the acid hydrolysis was of first order with respect to the acid concentration. The heterogeneous hydrolysis in alkaline medium followed a pseudo-first-order kinetics with respect to the base concentration; the hydrolysis rate was affected by the carbonate content and the structure of the carbonate units. The activation energies obtained for the acid and base catalyzed homogeneous hydrolysis and the base catalyzed heterogeneous hydrolysis were 13.8, 10.0, and 10.3 kcal/mol, respectively. α-Chymotrypsin was inactive in the hydrolysis experiments carried out with these copolymers. Es wurde die Kinetik der Verseifung von Vinylalkohol-Vinyl-n-alkylcarbonat Copolymeren in Abhangigkeit von der Saure- und Basen-Konzentration, der Temperatur und der Art der Carbonatgruppen untersucht. Die homogene basenkatalysierte Verseifung verlauft nach einer Reaktion erster Ordnung in bezug auf die Hydroxyl-und Carbonatgruppen-Konzentration, wahrend die saurekatalysierte Verseifung in Bezug auf die Saure-Konzentration eine Reaktion erster Ordnung ist. Die heterogene basenkatalysierte Verseifung hangt von der Konzentration und der Art der Carbonatgruppen ab. Fur die saure und basische homogene_Verseifung wurden Aktivierungsenergien von 13.8 und 10.0 kcal/mol erhalten. Fur die heterogene basenkatalysierte Verseifung ist eine Aktivierungsenergie von 10.3 kcal/mol erhalten worden. α-Chymotrypsin zeigte sich als unwirksam bei den hier durchgefuhrten Verseifungsreaktionen.