Baidya Avijit, Ghovvati Mahsa, Lu Cathy, Naghsh-Nilchi Hamed, Annabi Nasim
Department of Chemical and Biomolecular Engineering, University of California-Los Angeles, Los Angeles, California90095, United States.
Department of Bioengineering, University of California-Los Angeles, Los Angeles, California90095, United States.
ACS Appl Mater Interfaces. 2022 Oct 26. doi: 10.1021/acsami.2c11348.
Nitro-functionality, with a large deficit of negative charge, embraces biological importance and has proven its therapeutic essence even in chemotherapy. Functionally, with its strong electron-withdrawing capability, nitro can manipulate the electron density of organic moieties and regulates cellular-biochemical reactions. However, the chemistry of nitro-functionality to introduce physiologically relevant macroscopic properties from the molecular skeleton is unknown. Therefore, herein, a neurotransmitter moiety, dopamine, was chemically modified with a nitro-group to explore its influence on synthesizing a multifunctional biomaterial for therapeutic applications. Chemically, while the nitro-group perturbed the aromatic electron density of nitrocatecholic domain, it facilitated the suturing of nitrocatechol moieties to regain its aromaticity through a radical transfer mechanism, forming a novel macromolecular structure. Incorporation of the sutured-nitrocatecholic strand (S-nCAT) in a gelatin-based hydrogel introduced an electroconductive microenvironment through the delocalization of π-electrons in S-nCAT, while maintaining its catechol-mediated adhesive property for tissue repairing/sealing. Meanwhile, the engineered hydrogel enriched with noncovalent interactions, demonstrated excellent mechano-physical properties to support tissue functions. Cytocompatibility of the bioadhesive was assessed with and studies, confirming its potential usage for biomedical applications. In conclusion, this novel chemical approach enabled designing a multifunctional biomaterial by manipulating the electronic properties of small bioactive molecules for various biomedical applications.
硝基官能团带有大量负电荷缺失，具有生物学重要性，甚至在化疗中也已证明其治疗本质。在功能上，由于其强大的吸电子能力，硝基可以操纵有机部分的电子密度并调节细胞生化反应。然而，从分子骨架引入生理相关宏观性质的硝基官能团化学尚不清楚。因此，在此，一种神经递质部分多巴胺用硝基进行化学修饰，以探索其对合成用于治疗应用的多功能生物材料的影响。在化学方面，虽然硝基扰乱了硝基儿茶酚结构域的芳香电子密度，但它通过自由基转移机制促进了硝基儿茶酚部分的缝合以恢复其芳香性，形成了一种新型大分子结构。将缝合的硝基儿茶酚链（S-nCAT）掺入明胶基水凝胶中，通过S-nCAT中π电子的离域引入了导电微环境，同时保持其儿茶酚介导的用于组织修复/密封的粘附特性。同时，富含非共价相互作用的工程水凝胶表现出优异的机械物理性能以支持组织功能。通过细胞毒性和细胞增殖研究评估了生物粘合剂的细胞相容性，证实了其在生物医学应用中的潜在用途。总之，这种新颖的化学方法能够通过操纵小生物活性分子的电子性质来设计用于各种生物医学应用的多功能生物材料。
