Melanins are ubiquitous but their complexity and insolubility has hindered characterization of their structures and functions. We are developing electrochemical reverse engineering methodologies that focus on properties and especially on redox properties. Previous studies have shown that melanins (i) are redox-active and can rapidly and repeatedly exchange electrons with diffusible oxidants and reductants, and (ii) have redox potentials in midregion of the physiological range. These properties suggest the functional activities of melanins will depend on their redox context. The brain has a complex redox context with steep local gradients in O₂ that can promote redox-cycling between melanin and diffusible redox-active chemical species. Here, we performed in vitro reverse engineering studies and report that melanins can redox-cycle with two common redox-active drugs. Experimentally, we used two melanin models: a convenient natural melanin derived from cuttlefish (Sepia melanin) and a synthetic cysteinyldopamine–dopamine core–shell model of neuromelanin. One drug, acetaminophen (APAP), has been used clinically for over a century, and recent studies suggest that low doses of APAP can protect the brain from oxidative-stress-induced toxicity and neurodegeneration, while higher doses can have toxic effects in the brain. The second drug, clozapine (CLZ), is a second generation antipsychotic with polypharmacological activities that remain incompletely understood. These in vitro observations suggest that the redox activities of drugs may be relevant to their modes-of-action, and that melanins may interact with drugs in ways that affect their activities, metabolism, and toxicities.

中文翻译：

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止痛药对乙酰氨基酚和抗精神病药氯氮平可以与黑色素每个氧化还原循环。

黑色素无处不在，但是它们的复杂性和不溶性阻碍了其结构和功能的表征。我们正在开发电化学逆向工程方法论，该方法论着重于性质，尤其是氧化还原性质。先前的研究表明，黑色素（i）具有氧化还原活性，可以与可扩散的氧化剂和还原剂快速反复交换电子，并且（ii）在生理范围的中部具有氧化还原电位。这些性质表明黑色素的功能活性将取决于它们的氧化还原环境。大脑具有复杂的氧化还原环境，在O _2中存在陡峭的局部梯度可以促进黑色素与可扩散的氧化还原活性化学物质之间的氧化还原循环。在这里，我们进行了体外逆向工程研究，并报告黑色素可以与两种常见的氧化还原活性药物一起进行氧化还原循环。在实验上，我们使用了两种黑色素模型：一种从墨鱼（棕褐色）中提取的便捷天然黑色素黑色素）和神经半素的合成半胱氨酸多巴胺-多巴胺核-壳模型。对乙酰氨基酚（APAP）是一种药物，在临床上已经使用了一个多世纪，最近的研究表明，低剂量的APAP可以保护大脑免受氧化应激诱导的毒性和神经变性的影响，而高剂量的APAP可以对大脑产生毒性作用。第二种药物氯氮平（CLZ）是第二代抗精神病药，具有尚不完全了解的多药理活性。这些体外观察表明，药物的氧化还原活性可能与其作用方式有关，而黑色素可能以影响药物活性，新陈代谢和毒性的方式与药物相互作用。