The formation and reactivity of excited states and free radicals from primaquine, a drug used in the treatment of malaria, was studied in order to evaluate the primary photochemical reaction mechanisms. The excited primaquine triplet was not detected, but is likely to be formed with a short lifetime (<50 ns) and with a triplet energy <250 kJ/mol as the drug is an efficient quencher of the fenbufen triplet and the biphenyl triplet, and forms (1)O(2) by laser flash photolysis ((PQ)Phi(Delta)=0.025). Primaquine (PQ) exists as the monocation (PQH(+)) in aqueous solution at physiological pH. PQH(+) photoionises by a biphotonic process and also forms the monoprotonated cation radical (PQH(2+)*) by one electron oxidation by HO* (k(q)=6.6 x 10(9) M(-1) s(-1)) and Br*(2)(-) (k(q)=4.7 x 10(9) M(-1) s(-1)) at physiological pH, detected as a long-lived transient decaying essentially by a second order process (k(2)=7.4 x 10(8) M(-1) s(-1)). PQH(2+)* is scavenged by O(2), although at a limited rate (k(q)=1.0 x 10(6) M(-1) s(-1)). The reduction potential (E degrees) of PQH(2+)*/PQH(+) is < +1015 mV, as measured versus tryptophan (TRP*/TRPH). Primaquine also forms PQH(2+)* at pH 2.4, by one electron oxidation by Br*(2)(-) and proton loss (k(q)=2.7 x 10(9) M(-1) s(-1)). The non-protonated cation radical (PQ(+)*) is formed during one electron oxidation with Br*(2)(-) at alkaline conditions (k(q)=4.2 x 10(9) M(-1) s(-1) at pH 10.8). The estimated pK(a)-value of PQH(2+)*/PQ(+)* is pK(a) approximately 7-8. Primaquine is not a scavenger of O*(2)(-) at physiological pH. Thus self-sensitization by O*(2)(-) is eliminated as a degradation pathway in the photochemical reactions. Impurities in the raw material and photochemical degradation products initiate photosensitized degradation of primaquine in deuterium oxide, prevented by addition of the (1)O(2) quencher sodium azide. Photosensitized degradation by formation of (1)O(2) is thus important for the initial photochemical decomposition of primaquine, which also proceeds by free radical reactions. Formation of PQH(2+)* is expected to play an essential part in the photochemical degradation process in a neutral, aqueous medium.

译文

研究了用于治疗疟疾的药物伯喹的激发态和自由基的形成和反应性,以评估主要的光化学反应机制。未检测到激发的primaquine三重态,但很可能形成寿命短 (<50 ns),三重态能量 <250 kJ/mol,因为该药物是芬布芬三重态和联苯三重态的有效猝灭剂,并通过激光闪光光解形成 (1)O(2) ((PQ)Phi (δ) = 0.025)。Primaquine (PQ) 在生理pH下以水溶液中的单位置 (PQH ()) 存在。PQH(+) 通过双光子过程光电离,还通过HO * (k(q)= 6.6x10(9) M(-1) s(-1) 和Br *(2) 的一个电子氧化形成单质子化阳离子自由基 (PQH(2 +)*)(-) (k(q)= 4.7x10(9) M(-1) s(-1)) 在生理pH下,检测为基本上通过二阶过程衰减的长寿命瞬态 (k(2)= 7.4 × 10(8) M(-1) s(-1))。PQH(2 +)* 被O(2) 清除,尽管以有限的速率 (k(q)= 1.0 × 10(6) M(-1) s(-1))。与色氨酸 (TRP */TRPH) 相比,PQH(2 +)*/PQH(+) 的还原电位 (E度) <+ 1015 mV。在pH 2.4下,通过Br *(2)(-) 的一次电子氧化和质子损失 (k(q)= 2.7x10(9) M(-1) s(-1),伯喹也形成PQH(2 +)*。非质子化的阳离子自由基 (PQ(+)*) 在碱性条件下 (k(q)= 4.2 × 10(9) M(-1) s(-1)) 在用Br *(2)(-) 的一次电子氧化过程中形成。pH 10.8)。PQH(2 +)*/PQ(+)* 的估计pK(a)-值约为7-8。在生理pH下,Primaquine不是O *(2)(-) 的清除剂。因此,在光化学反应中,O *(2)(-) 的自敏化作为降解途径被消除。通过添加 (1)O(2) 猝灭剂叠氮化钠,防止了原料和光化学降解产物中的杂质引发氧化氘中primaquine的光敏化降解。因此,通过形成 (1)O(2) 的光敏降解对于primaquine的初始光化学分解很重要,primaquine也通过自由基反应进行。PQH(2) * 的形成有望在中性水性介质中的光化学降解过程中发挥重要作用。

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