基于奥沙拉嗪的金属有机框架作为 H2 吸附和药物递送的生物相容性平台,Journal of the American Chemical Society

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基于奥沙拉嗪的金属有机框架作为 H2 吸附和药物递送的生物相容性平台
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2016-08-03 , DOI: 10.1021/jacs.6b03523
Dana J. Levine , Tomče Runčevski ₁ , Matthew T. Kapelewski ₁ , Benjamin K. Keitz , Julia Oktawiec , Douglas A. Reed , Jarad A. Mason ₁ , Henry Z. H. Jiang ₁ , Kristen A. Colwell , Christina M. Legendre , Stephen A. FitzGerald ₂ , Jeffrey R. Long ₁

Affiliation

药物奥沙拉秦 (H4olz) 被用作配体来合成一系列新的介孔金属有机骨架，这些骨架是众所周知的 M2(dobdc) 材料 (dobdc(4-) = 2,5-dioxido-1) 的扩展类似物,4-苯二甲酸酯；M-MOF-74)。M2(olz) 框架（M = Mg、Fe、Co、Ni 和 Zn）具有高表面积，具有直径约为 27 Å 的大六边形孔。变温 H2 吸附等温线显示在开放金属位点处有强吸附，Mg2(olz) 和 Ni2(olz) 的原位红外光谱实验用于确定位点特异性 H2 结合焓。除了其气体吸附能力外，高度生物相容性的 Mg2(olz) 框架也被评估为用于递送奥沙拉嗪和其他封装疗法的平台。Mg2(olz) 材料（86 重量% 奥沙拉秦）显示出通过在模拟生理条件下溶解框架来释放治疗性接头。此外，Mg2(olz) 用于封装苯乙胺 (PEA)，这是一种广泛的生物活性化合物的模型药物。在模拟生理条件下，Mg2(olz)(PEA)2 分解以从孔中释放 PEA，并从框架本身释放奥沙拉秦，这表明多种治疗成分可以以不同的速率一起递送。低毒性、高表面积和配位不饱和金属位点使这些 M2(olz) 材料有望用于一系列潜在应用，包括在胃肠道疾病治疗中的药物递送。

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Olsalazine-Based Metal–Organic Frameworks as Biocompatible Platforms for H2Adsorption and Drug Delivery

The drug olsalazine (H4olz) was employed as a ligand to synthesize a new series of mesoporous metal-organic frameworks that are expanded analogues of the well-known M2(dobdc) materials (dobdc(4-) = 2,5-dioxido-1,4-benzenedicarboxylate; M-MOF-74). The M2(olz) frameworks (M = Mg, Fe, Co, Ni, and Zn) exhibit high surface areas with large hexagonal pore apertures that are approximately 27 Å in diameter. Variable temperature H2 adsorption isotherms revealed strong adsorption at the open metal sites, and in situ infrared spectroscopy experiments on Mg2(olz) and Ni2(olz) were used to determine site-specific H2 binding enthalpies. In addition to its capabilities for gas sorption, the highly biocompatible Mg2(olz) framework was also evaluated as a platform for the delivery of olsalazine and other encapsulated therapeutics. The Mg2(olz) material (86 wt % olsalazine) was shown to release the therapeutic linker through dissolution of the framework under simulated physiological conditions. Furthermore, Mg2(olz) was used to encapsulate phenethylamine (PEA), a model drug for a broad class of bioactive compounds. Under simulated physiological conditions, Mg2(olz)(PEA)2 disassembled to release PEA from the pores and olsalazine from the framework itself, demonstrating that multiple therapeutic components can be delivered together at different rates. The low toxicity, high surface areas, and coordinatively unsaturated metal sites make these M2(olz) materials promising for a range of potential applications, including drug delivery in the treatment of gastrointestinal diseases.

更新日期：2016-08-03

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