Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

Abstract

Conscious of the potential bioactivity of fluorine, an investigation was conducted using various fluorine-containing diaryliodonium salts in order to study and compare their biological activity against human lymphoma U937 cells. Most of the compounds tested are well-known reagents for fluoro-functionalized arylation reactions in synthetic organic chemistry, but their biological properties are not fully understood. Herein, after initially investigating 18 fluoro-functionalized reagents, we discovered that the ortho-fluoro-functionalized diaryliodonium salt reagents showed remarkable cytotoxicity in vitro. These results led us to synthesize more compounds, previously unknown sterically demanding diaryliodonium salts having a pentafluorosulfanyl (SF5) functional group at the ortho-position, that is, unsymmetrical ortho-SF5 phenylaryl-λ3-iodonium salts. Newly synthesized mesityl(2-(pentafluoro-λ6-sulfanyl)phenyl)iodonium exhibited the greatest potency in vitro against U937 cells. Evaluation of the cytotoxicity of selected phenylaryl-λ3-iodonium salts against AGLCL (a normal human B cell line) was also examined.

Studies of Halogen Bonding Induced by Pentafluorosulfanyl Aryl Iodides: A Potential Group of Halogen Bond Donors in a Rational Drug Design

“…MS (ESI) m / z : 353 [(M + Na) + ]. The product was consistent with previously reported characterization data [60].…”

“…The preparation of o -, m -, p -SF 5 -iodobenzenes ( 1a – c ), and 3,5-bis-SF 5 -iodobenzene ( 1d ) was achieved by the copper-catalyzed halogen exchange reaction of corresponding aryl-bromides according to our previous report [48,60]. We first simulated the electrostatic potential values for the iodine atoms of the targeted SF 5 -iodobenzenes, along with the corresponding values for NO 2 -iodobenzenes, pentafluoro-iodobenzene, and iodobenzene for comparisons.…”

“…As expected, 3,5-bis-SF 5 -iodobenzene ( 1d ) is the most efficient template to induce halogen bonding in SF 5 -iodobenzenes ( 1 ), equivalent to the well-known halogen bond donor 3,5-bis-NO 2 -iodobenzene. The 3,5-bis-substitution is also attractive for improved biological activity, as evidenced in medicinal research [45,60].…”

Studies of Halogen Bonding Induced by Pentafluorosulfanyl Aryl Iodides: A Potential Group of Halogen Bond Donors in a Rational Drug Design

“…1a-c), and 3,5-bis-pentafluorosulfanyl iodobenzene (3,5-bis-SF5-iodobenzene, 1d) was achieved by the copper-catalyzed halogen exchange reaction of corresponding aryl-bromides according to our previous report. [45,57] Figure 2). Encouraged by the results of these calculations, 13…”

Synthesis of Vicinal Trifluoromethanesulfonate Substituted Diaryliodonium Salts and Their Anti-bacterial Properties

“…的细胞毒性; 其中间位 SF 5 和氟多位点取代的二芳基碘 盐在 5 μm 的浓度下表现出 78%～94%的细胞毒性. 邻 位取代二芳基碘盐表现出更高的细胞毒性, 邻位 SF 5 取 代的二芳基碘盐在 5 μm 的浓度下表现高达出 98.9% 的 细胞毒性, 甚至在 1 μm 的低浓度下的细胞毒性也达到 66.9%; 邻位 CF 3 SO 2 取代的二芳基碘盐在 5 μm 的浓度 下表现出高达 98.6% 的细胞毒性 [6] . 值得注意的是, 邻 位取代的二芳碘盐化合物在 5 μm 的浓度下对正常人类 细胞(AGLCL)仅约为 50%的中等毒性; 这种对肿瘤细胞 和正常细胞的毒性选择性差异为抗肿瘤药物的研发提 供了新思路.…”