Dendrimeric pyridoxamine enzyme mimics

PAMAM dendrimers from generations 1-6 were synthesized with pyridoxamine in their core. They transaminated pyruvic and phenylpyruvic acids in water to alanine and phenylalanine, respectively, with Michaelis-Menten kinetics and high effectiveness compared with simple pyridoxamine. The largest dendrimers-similar in size to some globular proteins-were comparable in effectiveness to a previous polyethylenimine (PEI)-pyridoxamine catalyst, and to a protein-pyridoxamine catalyst, but not as effective as a previous PEI-pyridoxamine carrying lauryl hydrophobic groups. The new catalysts showed both general acid/base catalysis by their amino groups and hydrophobic binding of the phenylpyruvate substrate.     

Simultaneous determination of pyridoxal and pyridoxamine by different spectrofluorimetric techniques

Binary mixtures of pyridoxal and pyridoxamine can be resolved by using zero-crossing first derivative spectrofluorimetry, first devivative constant wavelength synchronous luminescence spectrometry and first derivative constant energy synchronous luminescence spectrometry. These methods do not require any previous separation steps. The lowest quantization limit is obtained with first derivative constant energy synchronous fluorescence (13.0 and 9.0 mug/1. for pyridoxal and pyridoxamine, respectively). The measurements were performed in aqueous medium at pH 7.0 provided by adding 0.05M phosphate buffer solution. In order to demonstrate the validity of these methods a complete and exhaustive statistical analysis of the experimental data was performed. Pyridoxal and pyridoxamine were determined by these methods in synthetic and real mixtures with good results.     

A potent polymer/pyridoxamine enzyme mimic

An enzyme mimic consisting of pyridoxamines covalently linked to polyethyleneimine carrying long-chain alkyl groups converts pyruvic acid to dl-alanine with as much as an 8000-fold acceleration relative to the reaction with simple pyridoxamine at the same pyridoxamine concentration. The acceleration by polymer is a strong function of the length of the alkyl chains that are appended. The polymer furnishes acid and base groups to catalyze the proton transfers that are involved in transamination.     

Synthesis of analogs of pyridoxal 5′-phosphate and pyridoxamine 5′-phosphate

The following analogs of pyridoxamine 5-phosphate (PAMP) have been synthesized by the direct phosphorylation of the corresponding amines: 2-nor-PAMP, 6-methyl-2-nor-PAMP, and 6-methyl-PAMP. A method for the synthesis of analogs of pyridoxal 5-phosphate (PLP) by the phosphorylation of the Schiff's bases of the corresponding aldehydes with p-phenetidine and subsequent hydrolysis on a sulfonated resin has been worked out. 2-Nor-PLP, 6-methyl-2-nor-PLP, and 6-methyl-PLP have been obtained with yields of 53–73%. The spectral properties of the compounds obtained have been investigated.The authors heartily thank Academician A. E. Braunshtein for his constant interest in this work and for valuable advice.     

Synthesis and antitumor activity of pyridoxine monoalkenyl derivatives

A convenient method for the synthesis of pyridoxine alkenyl derivatives by the Wittig reaction of [(2,8-dimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)methyl]triphenylphosphonium chloride with aldehydes was suggested. Some of the compounds obtained exhibit antitumor activity in vitro.     

Chemistry of pyridoxine in drug design

Russian Chemical Bulletin - Pyridoxine and its derivatives, pyridoxamine and pyridoxal, are the three main forms of vitamin B6, which play exceptionally important biological roles in living...     

New pharmaceutical salts containing pyridoxine

Two mixed crystals were obtained by crystallizing the active pharmaceutical ingredient pyridoxine [systematic name: 4,5‐bis(hydroxymethyl)‐2‐methylpyridin‐3‐ol, PN] with (E )‐3‐(4‐hydroxy‐3‐methoxyphenyl)prop‐2‐enoic acid (ferulic acid) and 4‐hydroxy‐3,5‐dimethoxybenzoic acid (syringic acid). PN and the coformers crystallize in the form of pharmaceutical salts in a 1:1 stoichiometric ratio, namely 3‐hydroxy‐4,5‐bis(hydroxymethyl)‐2‐methylpyridin‐1‐ium (E )‐3‐(4‐hydroxy‐3‐methoxyphenyl)prop‐2‐enoate, C₈H₁₂NO₃⁺·C₉H₉O₅⁻, and 3‐hydroxy‐4,5‐bis(hydroxymethyl)‐2‐methylpyridin‐1‐ium 4‐hydroxy‐3,5‐dimethoxybenzoate monohydrate, C₈H₁₂NO₃⁺·C₁₀H₁₁O₅⁻·H₂O, the proton exchange between PN and the acidic partner being supported by the differences of the pK _a values of the two components and by the C—O bond lengths of the carboxylate groups. Besides complex hydrogen‐bonding networks, π–π interactions between aromatic moieties have been found to be important for the packing architecture in both crystals. Hirshfeld surface analysis was used to explore the intermolecular interactions in detail and compare them with the interactions found in similar pyridoxine/carboxylic acid salts.     

Carbon acidity of the alpha-pyridinium carbon of a pyridoxamine analog

We report second-order rate constants of kDO = 120 dm(3) mol(-1) s(-1) and kB = 6.4 x 10(-4) dm(3) mol(-1) s(-1) for exchange for deuterium of the first alpha-methylene proton of the 4-(aminomethyl)pyridine dication in D2O at 25 degree C and I= 1.0 (KCl). These data are consistent with a carbon acid pKa between 17 and 19 for ionization of this simple carbon acid and they show that the effect of an alpha-pyridinium substituent on carbon acidity is similar to that of an alpha-ester substituent.     

Synthesis of analogs of pyridoxal 5′-phosphate and pyridoxamine 5′-phosphate

The following analogs of pyridoxamine 5′-phosphate (PAMP) have been synthesized by the direct phosphorylation of the corresponding amines: 2-nor-PAMP, 6-methyl-2-nor-PAMP, and 6-methyl-PAMP. A method for the synthesis of analogs of pyridoxal 5′-phosphate (PLP) by the phosphorylation of the Schiff's bases of the corresponding aldehydes with p-phenetidine and subsequent hydrolysis on a sulfonated resin has been worked out. 2-Nor-PLP, 6-methyl-2-nor-PLP, and 6-methyl-PLP have been obtained with yields of 53–73%. The spectral properties of the compounds obtained have been investigated.     

Spectrofluorimetric method for the determination of piroxicam and pyridoxine

A simple and highly selective method for the determination of piroxicam and pyridoxine (vitamin B6) in pharmaceutical formulations is presented. The approach is based on the combination of solid-phase extraction (SPE) and room-temperature fluorimetry (RTF). SPE under optimum pH conditions provides the separation between piroxicam and pyridoxine. The selectivity of analysis, the analytical figures of merit, and the accuracy of the method are demonstrated with the determination of piroxicam and pyridoxine in several pharmaceutical preparations.     

维生素B_6在微电极上的电化学行为及测定

用伏安法研究了维生素B6(VB6)在碳纤维微电极(CFME)上的电化学行为及其测定。以0.1 mol/L的邻苯二甲酸氢钾(pH 5)的缓冲液为底液,在最佳实验条件下,VB6在0.94 V(vs,SCE)的氧化峰峰电流与VB6在5.0×10-6~8.0×10-4mol/L范围内呈良好的线性关系,检出限为1.0×10-6mol/L(S/N=3)。方法用于药剂中的VB6的分析。     

Colorimetric determination of pyridoxine in pharmaceutical preparations

Summary The USP method for the determination of pyridoxine hydrochloride in pharmaceutical preparations has been modified to increase the stability of the colour, the speed of determination and the sensitivity. The reaction is carried out in propan-2-ol medium instead of water triethanolamine is used as the buffer, and iodine is used as oxidant when necessary. The colour is stable for about 45 min, the sensitivity of the reaction is greatly increased and the method takes only about a fifth of the time of the USP method.

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Kolorimetrische Bestimmung von Pyridoxin in pharmazeutischen Präparaten

Zusammenfassung Die USP-Methode zur Bestimmung von Pyridoxinhydrochlorid in pharmazeutischen Präparaten wurde modifiziert, um die Beständigkeit der Farbe, die Geschwindigkeit der Bestimmung und deren Empfindlichkeit zu verbessern. Statt in Wasser wird die Reaktion in Propan-2-ol durchgeführt, wobei Triethanolamin als Puffer und Jod — wenn nötig — als Oxydationsmittel verwendet werden. Die Farbe ist ungefähr 45 min beständig, die Empfindlichkeit der Reaktion stark verbessert und die zur Durchführung der Methode erforderliche Zeit beträgt etwa ein Fünftel im Vergleich zur USP-Methode.

     

Equilibrium studies of some divalent metal ions complexes with pyridoxol,pyridoxal and pyridoxamine

The interaction of vitamin B₆ compounds, pyridoxol, pyridoxal and pyridoxamine with metal ions Mn²⁺, Co²⁺, Ni²⁺ and Hg²⁺ are studied. Values for stability constants are evaluated and the reaction stiochiometries are investigated in aqueous 0.50 M KCl at 25°C. It is shown that only pyridoxamine possesses a fairly good affinity to interact with metal ions. A linear relation holds between the stability constants of the first complex and the ionization potential of the divalent metal ions.     

Theoretical study of the antioxidant properties of pyridoxine

Molecules acting as antioxidants capable of scavenging reactive oxygen species (ROS) are of utmost importance in the living cell. The antioxidative properties of pyridoxine (vitamin B6) have recently been discovered. In this study, we have analyzed the reactivity of pyridoxine toward the ROS (.-)OH, (.-)OOH, and (.-)O(2)- at the density functional theory level (functionals B3LYP and MPW1B95). Two reaction types have been studied as follows: addition to the aromatic ring atoms and hydrogen/proton abstraction. Our results show that (.-)OH is the most reactive species, while (.-)OOH displays low reactivity and (.-)O2(-) does not react at all with pyridoxine. The most exergonic reactions are those where (.-)H is removed from the CH(2)OH groups or the ring-bound OH group and range from -33 to -39 kcal/mol. The most exergonic addition reactions occur by attacking the carbon atoms bonded to nitrogen but with an energy gain of only 6 kcal/mol.