Valentina Bušić

An Efficient Synthesis of Pyridoxal Oxime Derivatives under Microwave Irradiation

Quaternary salts of pyridoxal oxime have been synthesized by the quaternization of pyridoxal oxime with substituted phenacyl bromides using microwave heating. Microwave-assisted rapid synthesis was done both in solvent (acetone) and under solvent-free conditions. Good to excellent yields (58%–94%) were obtained in acetone in very short reaction times (3–5 min) as well as in the solvent-free procedure (42%–78%) in very short reaction times (7–10 min) too. Effective metodologies for the preparation of pyridoxal oxime quaternary salts, having the advantagies of being eco-friendly, easy to handle, and performed in shorter reactions time are presented. The structure of compound 7, in which a 4-fluorophenacyl moiety is bonded to the pyridinium ring nitrogen atom, was unequivocally confirmed by the single-crystal X-ray diffraction method.

Occurence of pharmaceuticals in surface water

Pharmaceuticals constitute a large group of human and veterinary medicinal organic compounds which have long been used throughout the world. According to their therapeutic activity they are classified in several groups: antibiotics, analgesics/antipyretic, CNS (Central nervous system) drugs, cardiovascular drugs, endocrinology treatments, diagnostic aidadsorbable organic halogen compounds. Pharmaceuticals are designed to have a physiological effect on humans and animals in trace concentrations. Pharmaceuticals end up in soil, surface waters and eventually in ground water, which can be used as a source of drinking water, after their excretion (in unmetabolized form or as active metabolites) from humans or animals via urine or faeces. The possible fates of pharmaceuticals once they get into the aquatic environment are mainly three: (i) ultimately they are mineralized to carbon dioxide and water, (ii) the compound does not degrade readily because it is lipophilic and is partially retained in the sedimentation sludge and (iii) the compound metabolizes to a more hydrophilic molecule, passes through the wastewater treatment plant and ends up in receiving waters (which are surface waters, mainly rivers). These compounds exhibit the highest persistence in the environment. In recent years, and in particular after the use of the advanced measurement technologies, many pharmaceuticals have been identified worldwide and detected at ng/L levels (trace concentrations) in the aquatic environment, and are considered as an emerging environmental problem due to their continuous input and persistence in the aquatic ecosystem even at low concentrations.

Extensive Intramolecular and Intermolecular Interactions in Two Quaternary Salts of the Pyridoxal Oxime

Two derivatives of pyridoxal oxime (1) were prepared by quaternization of pyridoxal oxime with phenacyl bromide and 2-methoxyphenacyl bromide. The crystal structures of the 1-phenacyl-3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methylpyridinium bromide (2) and the novel 3-hydroxy-4-hydroxyiminomethyl-5-hydroxymethyl-2-methyl-1-(2′-methoxyphenacyl) pyridinium bromide (3) have been determined by X-ray diffraction method. The conformation of these two pyridoxal oxime phenacyl derivatives is locked by numerous intramolecular hydrogen bonds. The O–H···Br, C–H···Br and C–H···O hydrogen bonds in 2 and 3 form complex three-dimensional network. Supramolecular structure of 3 also contains C–H···π and π···π interactions which link neighbouring cations.Graphical AbstractIn two derivatives of pyridoxal oxime, discrete interplay between intramolecular and intermolecular interactions during the crystallization process influence on the conformation of the molecules.

Pyridoxal oxime derivative potency to reactivate cholinesterases inhibited by organophosphorus compounds

Organophosphorus (OP) nerve agents (sarin, tabun VX and soman) inhibit the enzyme acetylcholinesterase (AChE, EC 3.1.1.7) by binding to its active site while preventing neurotransmission in the cholinergic synapses. The protection and treatment of this kind of poisoning are still a challenge as we are yet to discover an antidote that would be effective in all cases of poisoning. To aid the search for more efficient antidotes, we evaluated the ability of nine pyridoxal oxime derivatives, prepared by a novel synthetic pathway, to reactivate recombinant human AChE and the related purified human plasma butyrylcholinesterase (BChE, EC 3.1.1.8) inhibited by VX, tabun and paraoxon. Oximes are derivatives of vitamin B6 bearing a phenacyl moiety attached to the quaternary nitrogen atom and having various substituents on the phenyl ring. As the results have shown, the tested oximes were in general more efficient in the reactivation of OP-inhibited BChE than AChE. The highest observed rate was in the case of VX-inhibited BChE reactivation, where kobs was 0.0087min-1 and the reactivation maximum of 90% was achieved within 5h. The cholinesterases displayed a binding affinity for these derivatives in a μmolar range no matter the substituent on their rings which was in accordance with the molecular modelling results showing a similar binding pattern for all oximes within the active site of both AChE and BChE. Such a positioning reveals also that hydroxy and a metoxy substituents at the vicinity of the oxime moiety present a possible steric hindrance explaining the reactivation results.

CHAPTER 9:The Chemistry and Biochemistry of Vitamin B6: Synthesis of Novel Analogues of Vitamin B6

Vitamin B6 is crucial to diverse metabolic processes in humans, animals, plants and microorganisms. This chapter describes the history, chemistry and biochemistry of vitamin B6. It examines the first total synthesis of vitamin B6 and the elucidation of its chemical structure. The chapter also seeks to summarise the present knowledge of novel syntheses of vitamin B6 derivatives, their diversity and bioavailability.