Institute of Organic Chemistry, University of Zürich , Winterthurerstrasse 190, 8057 Zürich, Switzerland.
J Med Chem. 2013 Dec 27;56(24):10171-82. doi: 10.1021/jm4016137. Epub 2013 Dec 12.
In tissue engineering, survival of larger constructs remains challenging due to limited supply of oxygen caused by a lack of early vascularization. Controlled release of oxygen from small organic molecules represents a possible strategy to prevent cell death under anoxic conditions. A comprehensive study of methylated pyridone-derived endoperoxides has led to the development of water-soluble molecules that undergo retro-Diels-Alder reactions in aqueous environment releasing oxygen in high yield and with half-lives of up to 13 h. These molecules in combination with vitamin C as singlet oxygen quencher significantly improved survival of 3T3 fibroblasts and rat smooth muscle cells challenged with oxygen-depleted conditions.
在组织工程中,由于早期血管化不足导致氧气供应有限,较大构建体的存活仍然具有挑战性。从小分子有机化合物中可控释放氧气是防止缺氧条件下细胞死亡的一种可行策略。对甲基吡啶酮衍生的内过氧化物的全面研究导致了水溶性分子的发展,这些分子在水相环境中经历逆狄尔斯-阿尔德反应,以高收率和长达 13 小时的半衰期释放氧气。这些分子与维生素 C 结合作为单线态氧猝灭剂,显著提高了在缺氧条件下受到挑战的 3T3 成纤维细胞和大鼠平滑肌细胞的存活率。