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

世界上很大一部分珊瑚礁面临灭绝的高风险。虽然大部分威胁是由于全球因素，但珊瑚礁的减少也可能因当地因素而大大加剧。最近的关注集中在氧苯酮，一种常见的防晒成分，由于观察到氧苯酮对成年珊瑚有毒，并降低了幼年珊瑚的存活率。产生这种毒性的原因尚不清楚，需要更好的了解才能设计出对珊瑚礁真正安全的可持续防晒霜。该研究项目将表征有机防晒成分或其代谢产物中对珊瑚产生光毒性的化学结构，重点关注五种最常见的有机防晒成分：氧苯酮，胡莫柳酯，辛水杨酸酯，奥西诺酯和双苯双丙烯。这种更好的理解将为设计新的和可持续的防晒成分奠定基础，这些成分不会表现出光毒性。核心假设是，与芳香羰基相邻的羟基（存在于五种化合物中的每一种中）的存在与否是防晒成分是否具有光毒性的关键决定因素。太阳光吸收形成芳香羰基的激发三重态，其可产生活性氧（ROS），导致光毒性。然而，羟基相邻的芳族羰基在羟苯酮，胡莫柳酯，和octisalate抑制活性氧的生产过程中，阳光照射通过淬灭激发态三重态。有初步证据支持的假设是，羟苯酮、胡莫柳酯和辛水杨酸酯本身没有光毒性，但珊瑚代谢使羟基糖基化，形成产生ROS的葡糖苷代谢物，因此具有光毒性。辛酯和双苯丙烯酸酯应该是直接光毒性的，因为它们缺乏与芳族羰基相邻的羟基。这项研究将使用硬珊瑚和软珊瑚，但主要使用海葵Aiptasia，这是一种很好的珊瑚模型系统;像珊瑚一样，Aiptasia是含有内共生光合藻类的珊瑚虫。目的1将通过以下方式表征氧苯酮光毒性的机制：（i）测试氧苯酮的存在是否仅在阳光的UV波段存在下导致死亡，（ii）定量宿主动物和/或共生藻类将氧苯酮转化为葡糖苷代谢物，（iii）和（iv）在阳光下测试葡萄糖苷代谢物的ROS产生（iii）体外和（iv）体内，和（v）定量暴露于葡萄糖苷类似物的死亡率。目的2将用胡莫柳酯、辛水杨酸酯、奥西诺酯和双苯丙烯酸酯重复这些实验，以表征这种机制与被认为是羟苯酮替代品的防晒组分的相关性。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夏季研究，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，讨论防晒霜中哪些成分需要监管，哪些成分与珊瑚礁保护区的管理相关。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值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.