CAS: Towards sustainable sunscreens: identifying chemical structures in sunscreens linked to phototoxicity in corals

世界上有很大一部分珊瑚礁面临着高度灭绝的风险。尽管这种威胁很大程度上是由全球因素造成的，但局部因素也会显著加剧珊瑚数量的减少。最近的关注集中在氧苯酮，一种常见的防晒成分，因为观察到奥苯酮对成年珊瑚有毒，并降低幼年珊瑚的存活率。这种毒性的原因尚不清楚，需要更好地了解，以便能够设计出对珊瑚礁真正安全的可持续防晒霜。这项研究项目将描述导致珊瑚光毒性的有机防晒霜成分或其代谢物中的化学结构，重点是五种最常见的有机防晒霜成分：氧苯酮、高盐、辛柳酸盐、辛氧酸盐和辛二烯。这一认识的提高将为设计新的、可持续的防晒成分奠定基础，这些成分不会表现出光毒性。中心假设是，与芳香族羰基相邻的羟基的存在或不存在(存在于五种化合物中)是防晒成分是否具有光毒性的关键决定因素。阳光吸收形成芳香族羰基的激发三重态，可产生活性氧物种(ROS)，从而导致光毒性。然而，氧苯酮、高盐和辛酸中与芳香族羰基相邻的羟基通过猝灭激发态三联体来抑制阳光照射下ROS的产生。这一假说得到了初步证据的支持，即氧苯宗、高盐和辛酸本身没有光毒性，但珊瑚的新陈代谢会将羟基糖基化，形成产生ROS的葡萄糖苷代谢物，从而具有光毒性。辛氧酸盐和辛烯应该是直接光毒性的，因为它们在芳香族羰基附近没有羟基。这项研究将同时使用硬珊瑚和软珊瑚的成虫，但主要使用海葵Aiptasia，这是一个具有良好特征的珊瑚模型系统；与珊瑚一样，Aiptasia是含有内共生光合藻的珊瑚虫。目的1通过(I)测试氧苯酮的存在是否只在阳光的UV波段存在时才导致死亡，(Ii)通过宿主动物和/或共生藻类将氧苯酮转化为糖苷代谢物，(Iii)和(Iv)测试在阳光下糖苷代谢物产生的ROS，(Iii)体外和(Iv)体内测试，以及(V)量化暴露于糖苷类似物的死亡率，来表征氧苯酮的光毒性机制。目标2将用高盐、辛柳酸盐、辛草酸盐和辛烯来重复这些实验，以表征这一机制与被认为是奥苯酮替代品的防晒成分的相关性。来自代表性不足群体的本科生和一名高中科学教师以及一名来自代表性不足群体的陪同学生将被招募参加暑期研究，方法是与现有的斯坦福大学项目合作。这项研究应该为政策讨论提供信息，说明哪些成分应该在防晒霜中进行监管，并与珊瑚礁保护区的管理相关。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

A large fraction of the world's coral reefs are at a high risk of extinction. Although much of the threat is due to global factors, coral declines can also be significantly exacerbated by local factors. Recent concern has focused on oxybenzone, a common sunscreen component, due to observations that oxybenzone is toxic to adult corals and reduces survival of juvenile coral. The reasons for this toxicity are unclear, and improved understanding is needed to enable the design of sustainable sunscreens that are truly safe for coral reefs. This research project will characterize the chemical structures within organic sunscreen components or their metabolites that are responsible for phototoxicity to corals, focusing on five of the most common organic sunscreen components: oxybenzone, homosalate, octisalate, octinoxate, and octocrylene. This improved understanding will lay the groundwork for the design of new and sustainable sunscreen components that do not exhibit phototoxicity. The central hypothesis is that the presence or absence of a hydroxyl group adjacent to the aromatic carbonyl (present in each of the five compounds) is a critical determinant of whether a sunscreen component is phototoxic. Sunlight absorption forms excited triplet states of aromatic carbonyls that can generate Reactive Oxygen Species (ROS), resulting in phototoxicity. However, the hydroxyl group adjacent to the aromatic carbonyl in oxybenzone, homosalate, and octisalate inhibits ROS production during sunlight illumination by quenching excited-state triplets. The hypothesis, backed by preliminary evidence, is that oxybenzone, homosalate, and octisalate themselves are not phototoxic, but that coral metabolism glycosylates the hydroxyl groups to form glucoside metabolites that produce ROS and are thus phototoxic. Octinoxate and octocrylene should be directly phototoxic because they lack a hydroxyl group adjacent to the aromatic carbonyl. The research will employ both hard- and soft-coral adults but mainly use the sea anemone Aiptasia, a well characterized model system for corals; like corals, Aiptasia are anthozoans containing endosymbiotic photosynthetic algae. Objective 1 will characterize the mechanism of oxybenzone phototoxicity by: (i) testing whether the presence of oxybenzone leads to mortality only in the presence of the UV wavebands of sunlight, (ii) quantifying the conversion of oxybenzone to glucoside metabolites by the host animal and/or the symbiotic algae, (iii and iv) testing for ROS production under sunlight from glucoside metabolites (iii) in vitro and (iv) in vivo, and (v) quantifying mortality from exposure to glucoside analogues. Objective 2 will replicate these experiments with homosalate, octisalate, octinoxate, and octocrylene to characterize the relevance of this mechanism to sunscreen components being considered as alternatives to oxybenzone. Undergraduate students from underrepresented groups and a high-school science teacher with an accompanying student from an underrepresented group will be recruited to participate in summer research by partnering with existing Stanford University programs. The research should inform policy discussions about which components to regulate in sunscreens and be relevant to the management of coral-reef reserves.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.