Assessment of Photoreleasable Linkers and Light-Capturing Antennas on a Photoresponsive Cobalamin Scaffold.
Assessment of Photoreleasable Linkers and Light-Capturing Antennas on a Photoresponsive Cobalamin Scaffold.
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DOI：
10.1021/acs.joc.1c02931
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发表时间：
2022-04-15
影响因子：
3.6
通讯作者：
Lawrence, David S.
中科院分区：
文献类型：
--
作者：
Welfare, Joshua G.;Mortelliti, Michael J.;McGlade, Caylie A.;Hartman, Timothy W.;Dempsey, Jillian L.;Lawrence, David S.
钴胺素由于其易于修饰和药物光释放的高量子产率而显示出作为光敏药物递送平台的前景。然而，到目前为止，对烷基钴的一般光化学的研究主要集中在甲基和腺苷取代的衍生物，存在于各种酶物种中的天然辅因子。我们描述了由荧光团和β-轴配体的不同组合组成的钴胺素缀合物的合成和光解行为。通常，含有β-轴烷基取代基的钴胺素缀合物在水性条件下经历有效的光解，量子产率高达> 40%。然而，大的和疏水的取代基，或不能容易地支持假定的自由基中间体，比较小的水溶性类似物遭受更低效率的光解（<15%）。相比之下，量子产率提高了2倍，在DMF中的钴含有大的疏水性双轴取代基。这表明，药物从由膜隔室组成的载体（如脂质体）中的释放可能比在水性环境中的相应光释放显著更有效。最后，我们探讨了组织模拟条件下的烷基钴的光解的荧光团的影响。用有效的光子捕获荧光团取代的钴酸盐相对于未取代的衍生物在光解方面显示高达4倍的增强。总之，我们已经表明，烷基钴胺素缀合物的光敏性可以通过改变Co附加的烷基部分，调节环境（溶剂）的极性，并安装到钴胺素框架上的光子捕获荧光团来调节。
Cobalamin has shown promise as a light-sensitive drug delivery platform owing to its ease of modification and the high quantum yields for drug photorelease. However, studies to date on the general photochemistry of alkyl-cobalamins have primarily focused on methyl and adenosyl-substituted derivatives, the natural cofactors present in various enzymatic species. We describe the synthesis and photolytic behavior of cobalamin conjugates comprised of different combinations of fluorophores and β-axial ligands. In general, cobalamin conjugates containing β-axial alkyl substituents undergo efficient photolysis under aqueous conditions, with quantum yields up to >40%. However, substituents that are large and hydrophobic, or unable to readily support the presumed radical intermediate, suffer less efficient photolysis (<15%) than smaller, water soluble, analogs. By contrast, quantum yields improve by two-fold in DMF for cobalamins containing large hydrophobic ß-axial substituents. This suggests that drug release from carriers comprised of membranous compartments, such as liposomes, may be significantly more efficient than the corresponding photorelease in an aqueous environment. Finally, we explored the impact of fluorophores on the photolysis of alkyl-cobalamins under tissue mimetic conditions. Cobalamins substituted with efficient photon-capturing fluorophores display up to 4-fold enhancements in photolysis relative to unsubstituted derivatives. In summary, we’ve shown that the photosensitivity of alkyl-cobalamin conjugates can be tuned by altering the Co-appended alkyl moiety, modulating the polarity of the environment (solvent), and installing photon-capturing fluorophores onto the cobalamin framework.
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DOI：
10.1039/jr9640003186
发表时间：
1964-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY
影响因子：
--
作者：
DOLPHIN, D;JOHNSON, AW;RODRIGO, R
通讯作者：
RODRIGO, R
影响因子：
2.9
作者：
Jost, Marco;Simpson, Jeffrey H.;Drennan, Catherine L.
通讯作者：
Drennan, Catherine L.
影响因子：
62.1
作者：
Klan, Petr;Solomek, Tomas;Bochet, Christian G.;Blanc, Aurelien;Givens, Richard;Rubina, Marina;Popik, Vladimir;Kostikov, Alexey;Wirz, Jakob
通讯作者：
Wirz, Jakob
影响因子：
2.9
作者：
CHEN, E;CHANCE, MR
通讯作者：
CHANCE, MR
影响因子：
3
作者：
BERNETT, WA
通讯作者：
BERNETT, WA