C. Camargo

Oxidation of Hantzsch 1,4-dihydropyridines of pharmacological significance by electrogenerated superoxide.

AbstractPurpose. To study the reaction of a series of Hantzsch dihydropyridines with pharmacological significance such as, nifedipine, nitrendipine, nisoldipine, nimodipine, isradipine and felodipine, with electrogenerated superoxide in order to identify products and postulate a mechanism. Methods. The final pyridine derivatives were separated and identified by gas chromatography/mass spectrometry (GC-MS). The intermediates, anion dihydropyridine and the HO2•/ HO2− species, were observed from voltammetric studies and controlled potential electrolysis was used to electrogenerate O2•−. Results. The current work reveals that electrogenerated superoxide can quantitatively oxidize Hantzsch dihydropyridines to produce the corresponding aromatized pyridine derivatives. Conclusions. Our results indicate that the aromatization of Hantzsch dihydropyridines by superoxide is initiated by proton transfer from the N1-position on the 1,4-dihydropyridine ring to give the corresponding anion dihydropyridine, which readily undergoes further homogeneous oxidations to provide the final aromatized products. The oxidation of the anionic species of the dihydropyridine is more easily oxidized than the parent compound.

Simultaneous determination of melatonin and pyridoxine in tablets by gas chromatography-mass spectrometry

A gas chromatographic-mass spectrometric (GC-MS) method for the qualitative and quantitative determination of melatonin plus pyridoxine commercial tablets is described. Melatonin and pyridoxine were simultaneously determined by GC-MS after extraction from ground tablets with methanol and derivatization with N-methyl-N-N-trimethlylsilyltrifluoroacetamide (MSTFA). The mass chromatograms were generated using 232 m/z ion for melatonin and 280 m/z ion for pyridoxine, respectively. Splitless injection offers good reproducibility with a standard deviation of 2%. The developed method was applied to analyze the melatonin and pyridoxine content from two different tablet formulations. Also, recovery, detection and quantification limits are reported.

Electrochemical and EPR Characterization of 1,4-dihydropyridines. Reactivity Towards Alkyl Radicals

This work reports the electrochemical oxidation of a series of three synthesized 4-substituted-1,4-dihydropyridine derivatives in different electrolytic media. Also, an EPR characterization of intermediates and the reactivity of derivatives towards ABAP-derived alkyl radicals are reported. Dynamic, differential pulse and cyclic voltammetry studies on a glassy carbon electrode showed an irreversible single-peak due to the oxidation of the 1,4-dihydropyridine (1,4-DHP) ring via 2-electrons to the corresponding pyridine derivative. Levich plots were linear in different media, indicating that the oxidation process is diffusion-controlled. Calculated diffusion coefficients did not exhibit significant differences between the derivatives in the same medium. The oxidation mechanism follows the general pathway (electron, H + , electron, H + ) with formation of an unstable pyridinium radical. One-electron oxidation intermediate was confirmed with controlled potential electrolysis (CPE) and EPR experiments. On applying N-tert-butyl- f -phenylnitrone (PBN) and 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as the spin trap, these unstable radical intermediates from the oxidation of 1,4-DHP derivatives were intercepted. The final product of the CPE, i.e. pyridine derivative, was identified by GC-MS technique. Direct reactivity of the synthesized compounds towards alkyl radicals was demonstrated by UV-Vis. spectroscopy and GC-MS technique. Results indicate that these derivatives significantly react with the radicals, even compared with a well-known antioxidant drug such as nisoldipine.

Reactivity of 1,4-dihydropyridines toward SIN-1-derived peroxynitrite

AbstractPurpose. To study the reactivity of C4-substituted 1,4-dihydropyri- dines (1,4-DHP), with either secondary or tertiary nitrogen in the dihydropyridine ring, toward SIN-1-derived peroxynitrite in aqueous media at pH 7.4. Methods. Reactivity was followed by changes in the absorptivity of the UV-Vis bands corresponding to 1,4-DHP. Gas Chromatography/Mass Spectrometer (GC-MS) and Electron Paramagnetic Resonance (EPR) spin trap techniques were used to characterize the final product and the intermediates of the reaction, respectively. Results. 1,4-DHPs significantly reacted toward peroxynitrite at varied rates, according to the calculated kinetic rate constants. By EPR spectroscopy, a carbon-centered radical from the 1,4-DHP was intercepted with N-tert-butylamine-α-phenylnitrone (PBN), as the intermediate for the reaction with peroxynitrite. Likewise, the oxidized derivative (i.e., the pyridine) was identified as the final product of the reaction by GC-MS. By using the technique of deuterium kinetic isotope effect, the participation of the hydrogen of the 1-position on the 1,4-DHP ring was shown not to be the rate-limiting step of the reaction. Conclusions. The direct participation of the 1,4-DHP derivatives in the quenching of SIN-1-derived peroxynitrite has been demonstrated. Kinetic rate constant of tested 1,4-DHP toward peroxynitrite showed a direct relationship with the oxidation peak potential values; that is, compounds reacting faster were more easily oxidized.

Analysis of 25 C NBOMe in Seized Blotters by HPTLC and GC–MS

Use of unauthorized synthetic drugs is a serious, forensic, regulatory and public health issue. In this scenario, consumption of drug-impregnated blotters is very frequent. For decades, blotters have been generally impregnated with the potent hallucinogen known as lysergic acid diethylamide (LSD); however, since 2013 blotter stamps with N-2 methoxybenzyl-substituted phenylethylamine hallucinogen designated as “NBOMes” have been seized in Chile. To address this issue with readily accessible laboratory equipment, we have developed and validated a new HPTLC method for the identification and quantitation of 25-C-NBOMe in seized blotters and its confirmation by GC–MS. The proposed method was validated according to SWGTOX recommendations and is suitable for routine analysis of seized blotters containing 25-C-NBOMe. With the validated method, we analyzed 15 real samples, in all cases finding 25-C-NBOMe in a wide dosage range (701.0–1943.5 µg per blotter). In this situation, we can assume that NBOMes are replacing LSD as the main hallucinogenic drug consumed in blotters in Chile.

Electrolytic Oxidation of C4-Nitrofuryl 1,4-Dihydropyridines in Nonaqueous Medium

A study of the electrolytic oxidation of three new C-4 nitrofuryl 1,4-dihydropyridines in nonaqueous aprotic medium is presented. Controlled-potential electrolysis (CPE) in dimethylformamide +0.1 M tetrabutyl-ammonium hexafluorophosphate (TBAPF 6 ) was followed by UV-visible spectroscopy, high-performance liquid chromatography (HPLC)-photodiode array (PDA), and gas chromatography-Mossbauer spectroscopy (GC-MS) chromatography, and electron spin resonance and electrochemical techniques. Carbon-centered radical intermediates produced in the electrochemical oxidation of C-4 nitrofuryl substituted 1,4-dihydropyridines were trapped with N-benzylidene-tert-butylamine-N-oxide (PBN) and their splitting constants were calculated. The neutral pyridine derivatives were identified by GC-MS techniques as final oxidation products. HPLC-PDA and GC-MS chromatographic techniques were used to follow the time-course of CPE of both parent 1,4-DHP derivatives and their respective oxidation products. Also, an overall oxidation mechanism of C-4 nitrofuryl-1,4-DHP derivatives is presented.

1,4-Dihydropyridines: Reactivity of Nitrosoaryl and Nitroaryl Derivatives with Alkylperoxyl Radicals and ABTS Radical Cation

In the present paper, a direct quenching of radical species by a number of synthesized nitrosoaryl 1,4-dihydropyridines and their parent nitroaryl 1,4-dihydropyridines was determined in aqueous media at pH 7.4. These two series of compounds were compared with the C-4 unsubstituted 1,4-dihydropyridines derivatives and the corresponding C-4 aryl substituted 1,4-dihydropyridines derivatives. Kinetic rate constants were assessed by UV-Vis spectroscopy. Nitrosoaryl derivatives were more reactive than the parent nitroaryl 1,4-dihydropyridines. Our results strongly support the assumption that the reactivity between the synthesized 1,4-dihydropyridines derivatives with alkylperoxyl radicals involves electron transfer reactions, which is documented by the presence of pyridine as final product of reaction and the complete oxidation of the nitroso group to give rise the nitro group in the case of the nitrosoaryl 1,4-dihydropyridines derivatives.

Analysis of a New Potent Hallucinogen, 25-B-NBOMe, in Blotters by High-Performance Thin-Layer Chromatography

All over the world, hallucinogens have long been abused to experience their effects; in this context, abuse of drugs is a serious public health issue. Because the consumption of blotters impregnated with drug is very frequent, hallucinogens are the most common drugs found in blotters [1]. Since decades, blotters have been generally impregnated with the potent hallucinogen known as lysergic acid diethylamide (LSD). This substance is considered as a low toxic hallucinogen; however, for a couple of years, numerous blotters have been seized in Chile and other countries with N-(2-methoxy)benzyl-substituted phenylethylamine hallucinogens, designated as NBOMe derivatives [2]. The structural analogues of substituted phenylethylamine are a group of newly synthesized chemical compounds and, according to scientific studies, demonstrate a high affinity for 5HT2A receptor; international reports indicate that it even could be higher than the LSD [3]. These new drugs are represented essentially by three compounds known as 25 I NBOMe, 25 C NBOMe, and 25 B NBOMe if they contain iodine, chlorine, or bromine in their structure (Figure 1 shows these chemical structures) [4]. Numerous reports of deaths and hospitalizations related to the consumption of these new synthetic compounds impregnated in blotters have occurred in the United States and Europe [5, 6]. In this situation and in order to determine the con-