Publisher Summary This chapter discusses those drugs where one or more photoderivatives have been positively identified and photosensitizers which, although unchanged themselves, photocatalyse the degradations of biomolecules. Precautions against the photodegradation of drugs in storage are easily taken, but light-induced changes after the patient has taken the medicine may lead to serious side-effects––typically erythema, oedema, and vesicle formation of exaggerated sunburn. Sunlight penetrates the skin to a depth sufficient to reach blood circulating in surface capillaries. Two types of photosensitivity as a result of foreign chemicals circulating in the blood stream has been described––namely, phototoxicity and photoallergy. In phototoxicity, the excited state of the drug molecule can induce cellular damage in at least one of three ways: by inducing radical formation in an endogenous molecule, by converting oxygen from its ground (triplet) to the highly toxic singlet state, or by electron transfer, it can generate the very reactive superoxide radical. Phototoxicity occurs only in areas of skin exposed to the light and is characterized by the relief of symptoms when the drug is withdrawn. It can be effective with only one dose in combination with exposure to the sun (or an ultraviolet lamp). With a high enough dose, the phototoxic response can be elicited from all exposed individuals. Examples of drugs that can generate singlet oxygen are chloroquine, frusemide, nalidixic acid, and naproxen. Superoxide generators are chlorpromazine, mercaptopurine, some tetracyclines, and psoralens.

Photodecomposition of drugs.

Kinetics of racemization of (+)- and (-)-diethylpropion: studies in aqueous solution, with and without the addition of cyclodextrins, in organic solvents and in human plasma.

4-Nitrobenzyl(α-amino)phosphonic acids treated with an excess of aqueous sodium hydroxide undergo a C-P bond cleavage and subsequent transformation into a mixture of azoxybenzene and azobenzene derivatives. The observed cleavage is an example of the intramolecular redox reaction. The phosphonate moiety is oxidized to phosphate, and the remaining part of the molecule is reduced to azoxybenzene derivative 2. After acidification of the reaction mixture two main products were isolated; 4,4′-diformylazoxybenzene (3) and 4-formyl-4′-hydroxyazobenzene (4). The product 4 was probably formed as a result of the Wallach type rearrangement of 3.

NITROBENZYL(α-AMINO)PHOSPHONATES. PART 2[1]. CLEAVAGE OF 4-NITROBENZYL(α-AMINO)PHOSPHONIC ACIDS IN AQUEOUS SODIUM HYDROXIDE SOLUTION

High-Performance Liquid Chromatographic Determination of Diethylpropion Hydrochloride in Tablets: Isolation and Identification of Two Decomposition Products

Unter Lichteinwirkung werden wasrige D-(−)-Methadon-Hydrochlorid-Losungen weitgehend zersetzt. Radikalische α-Spaltung, γ-Wasserstoff-Abstraktion und eine Photocyclisierung – die zum 3,3-Diphenyl-2-athyliden-5-methyltetrahydrofuran fuhrt – konnten als primare Abbaumechanismen wahrscheinlich gemacht werden. Die auf diesen Wegen entstandenen Photoprodukte sind zum Teil selbst instabil und fragmentieren in Formaldehyd, Acetaldehyd, Glyoxal, Aceton, Methylglyoxal, Brenztraubensaure, Benzophenon, Benzpinakon und Benzaldehyd.



Fragmentation of D-(−)-Methadone Hydrochloride by Light



Under the influence of light, aqueous solutions of D-(−)-methadone hydrochloride undergo decomposition to a great extent. Radical α-cleavage, γ-hydrogen-abstraction and photocyclisation – leading to 3,3-diphenyl-2-ethylidene-5-methyltetrahydrofuran – have been shown to be probable primary degradation mechanisms. Some of the photoproducts formed are unstable and undergo fragmentation to formaldehyde, acetaldehyde, glyoxal, acetone, methylglyoxal, pyruvic acid, benzophenone, benzpinacone and benzaldehyde.

[Light-induced fragmentation of D-(-)-methadone hydrochloride in aqueous solution].

Chloramphenicol zerfallt in wasriger Losung durch Photo-β-Spaltung in ein aromatisches (I) und ein aliphatisches (II) Radikal. I stabilisiert sich zu p-Nitrobenzaldehyd, II zu Glykolaldehyd und Dichloracetamid. p-Nitrobenzaldehyd wird in einer Folge von Licht- und Dunkelreaktionen zu p,p′-Azoxybenzoesaure, p-Aminobenzaldehyd und p-Aminobenzoesaure photoreduziert, bei „oxygen quenching” vornehmlich zu p-Nitrobenzoesaure oxidiert. In Gegenwart von 1,3-Butandiol reagiert der primar gebildete p-Nitrobenzaldehyd zu 2-(p-Nitrophenyl)-4-methyl-1,3-dioxan. Werden wasrige Chloramphenicol-Losungen γ-Strahlen ausgesetzt, so finden sich im wesentlichen die gleichen Abbauprodukte wie bei der Photolyse. In kristallinem Zustand ist Chloramphenicol stabiler; in geringem Umfang erfolgt auch hier strahleninduzierte β-Spaltung.



Photolysis and Radiolysis of Chloramphenicol



In aqueous solution chloramphenicol undergoes decomposition into an aromatic (I) and an aliphatic (II) radical through photo-β-cleavage. I stabilizes itself to p-nitrobenzaldehyde, II to glycol aldehyde and dichloroacetamide. Through a sequence of photosensitized and non photosensitized reactions, p-nitrobenzaldehyde is reduced to p,p′-azoxybenzoic acid, p-aminobenzaldehyde and p-amino-benzoic acid; through “oxygen quenching” it undergoes oxidation, mainly to p-nitrobenzoic acid. In presence of 1,3-butandiol the primarily formed p-nitrobenzaldehyde is transformed to 2-(p-nitrophenyl)-4-methyl-1,3-dioxane. If aqueous chloramphenicol solutions are subjected to γ-rays, degradation products similar to those produced through photolysis are formed. Chloramphenicol is more stable in the crystalline state; also here photoinduced β-cleavage takes place to a limited extent.

Photo‐ und Radiolyse des Chloramphenicols

P-Nitrobenzaldehyd unterliegt in wasriger Losung der Photoisomerisation zu p-Nitrosobenzoesaure. Bei Anwesenheit geeigneter Wasserstoffdonatoren entsteht p,p′-Azoxybenzoesaure. In methanolischer Losung wird der Dimethylester der p,p′-Azoxybenzoesaure gebildet; die Reaktion durfte uber die Zwischenstufen p-Nitrobenzaldehyd-dimethylacetal und p-Nitrosobenzoesauremethylester verlaufen.



Photochemistry of p-Nitrobenzaldehyde



P-Nitrobenzaldehyde undergoes, in aqueous solution, photoisomerisation to p-nitrosobenzoic acid. In presence of suitable hydrogen donors, p,p′-azoxybenzoic acid is formed. In methanolic solution, the dimethyl p,p′-azoxybenzoate is produced; the reaction proceeds through the intermediates p-nitrobenzaldehyde-dimethylacetal and methyl p-nitrosobenzoate.

Photochemie des p‐Nitrobenzaldehyds

Photo- und Radiumbestrahlung wasriger und methanolischer 2-Diathylamino-propiophenon-(HCl)-Losungen fuhren zur Homolyse der C-2/N-Bindung unter Bildung der Radikale 6 und 7. 6 stabilisiert sich durch Disproportionierung und ergibt letztlich Athylamin, Diathylamin und Acetaldehyd. 7 geht uber eine intermolekulare Wasserstoffverschiebung in Propiophenon uber.



Photo- und Radium-Irradiated Fragmentation of 2-Diethylaminopropiophenone-HCl



Photo- and radium-irradiation of aqueous and methanolic solutions of 2-diethylaminopropiophenone-HCl lead to homolysis of the C-2/N bond with the formation of radicals 6 and 7. 6 stabilises itself by disproportionation giving finally ethylamine, diethylamine and acetaldehyde. 7 gives rise to propiophenone by an intermolecular hydrogen shift.

Photo- und Strahleninduzierte Fragmentierung des 2-Diäthylamino-propiophenon-HCl (Regenon®)†‡

Die C-CI-Bindungen des Dichloracetamids unterliegen der Photodissoziation, die zum Glyoxylsaureamid fuhrt, das in Glyoxylsaure und Ammoniak hydrolysiert. Glyoxylsaure disproportioniert in einer Photo-Cannizzaro-Reaktion in Oxalsaure und Glykolsaure.



Photochemistry of Dichloroacetamide



The C-CI-bond in dichloroacetamide suffers photo-dissociation leading to the formation glyoxalic acid amide. This is turn undergoes hydrolysis to glyoxalic acid and ammonia. Glyoxalic acid disproportionates into oxalic acid and glycolic acid through a photo-Cannizzaro-reaction.

K. G. Weidmann

Papers

Photo‐ und Radiolyse des Chloramphenicols

Photochemie des p‐Nitrobenzaldehyds

Photo- und Strahleninduzierte Fragmentierung des 2-Diäthylamino-propiophenon-HCl (Regenon®)†‡

Notiz zur Photochemie des Dichloracetamids

Photo- und strahlen-induzierte fragmentierung des 2-diaethylamino-propiophenonhydrochlorids (regenon (r))