Cao Phuong-Lien Doan, Chau Nguyen Khiem, Nevzorov Alexander A, Jovanovic Milena, Nalaoh Phattananawee, Lindsey Jonathan S
Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States.
Department of Chemistry, University of Tennessee, Knoxville, Tennessee 37996, United States.
J Org Chem. 2025 Jan 10;90(1):146-157. doi: 10.1021/acs.joc.4c02059. Epub 2024 Dec 20.
Aqueous solubilization of porphyrins, often accomplished with appended polar aryl groups, can also be achieved with symmetrically branched alkyl (i.e., swallowtail) groups terminated with polar moieties. Here, carboxylic acids are employed as termini (versus prior phosphono- or phosphoester termini) in designs of -AB-porphyrins bearing a single swallowtail group (A) or -A-porphyrins bearing two swallowtail groups. Variable-temperature H NMR studies (-60 to 97 °C) revealed that the 4-heptanedioic acid group at the meso-position of the free base porphyrin rotates with rate constant 5 s (310 K) and Arrhenius energy barrier = 11.5 kcal/mol, whereas an isopropyl group undergoes rotation ∼1000-times faster ( = 5770 s). The interconversion is sufficiently fast that conformational diastereomers, as when two such swallowtail groups are present in a -A-porphyrin, would not be isolable at room temperature (Class I atropisomers). DFT calculations (4 porphyrins containing the isopropyl or 4-heptanedioic acid groups) showed that the lowest energy conformer contains the swallowtail C-H unit in the plane of the porphyrin. The presence of one or two 4-heptanedioic acid moieties imparted solubility of the porphyrin in phosphate-buffered saline (PBS). The results suggest applications in the life sciences where compact, aqueous-soluble porphyrins are desired.
卟啉的水相增溶通常通过连接极性芳基来实现，也可以通过带有极性部分的对称支链烷基（即燕尾形）基团来实现。在这里，在设计带有单个燕尾形基团的-AB-卟啉或带有两个燕尾形基团的-A-卟啉时，使用羧酸作为末端基团（与之前的膦酸或磷酸酯末端基团相对）。变温¹H NMR研究（-60至97°C）表明，游离碱卟啉中位的4-庚二酸基团以速率常数5 s⁻¹（310 K）旋转，阿仑尼乌斯能垒ΔG‡ = 11.5 kcal/mol，而异丙基的旋转速度快约1000倍（k = 5770 s⁻¹）。这种相互转化足够快，以至于当一个-A-卟啉中存在两个这样的燕尾形基团时，构象非对映异构体在室温下无法分离（I类阻转异构体）。DFT计算（4种含有异丙基或4-庚二酸基团的卟啉）表明，能量最低的构象异构体在卟啉平面内含有燕尾形C-H单元。一个或两个4-庚二酸部分的存在赋予了卟啉在磷酸盐缓冲盐水（PBS）中的溶解性。结果表明，在需要紧凑的水溶性卟啉的生命科学领域有应用前景。
