Ionic liquids based on biologically active 1-(3-aminopropyl)silatrane and aryl(hetaryl)oxy(sulfanyl)(sulfonyl)acetic acids

Abstract

Nontoxic biologically active 1 organylsilatranes are widely used in medicine and agriculture.1 The first repre sentative of ionic liquids (IL) with the silatranyl fragment [MeEt2N (CH2)3Si(OCH2CH2)3N]•I –, possessing anti microbial and tuberculostatic activity, has been synthe sized 40 years ago by the reaction of 1 (3 diethylamino propyl)silatrane with MeI.2 Later, its analog containing a Me3N + group was obtained, which inhibited invasion of the human lung carcinoma cells A549 in vitro.3 In order to obtain new potentially biologically active IL, we applied mild conditions (15 C, 10 min) to carry out a reaction of 1 (3 aminopropyl)silatrane (1) with acet ic acid (2) and biologically active aryl(hetaryl)oxy (sulfanyl)(sulfonyl)acetic acids 3—7 (Scheme 1). Earlier, we used 2 methylphenyloxy (3), 4 chloro 2 methyl phenyloxy (4), 4 chlorophenylsulfanyl (5), 4 chloro phenylsulfonyl (6), 3 indolylsulfanyl (7) acetic acids and 2 hydroxyethylamines in the development of such medic inal remedies and biological agents as "trecrezan", "chloro crezacin", "sulfacetamine", "indacetamine", etc., which had the structure of (2 hydroxyethyl)ammonium IL: [(HOCH2CH2)nN +H]•[–OOCR]. The latter, being low toxic (LD50 = 1300—6000 mg kg –1), possess antiaggrega tion, membrane stabilizing, antisclerosis, immunomodu lating, adaptogenic, antitumor activity and are protectors from ultrasonic and  irradiation.4—14 Note that acids 3—7, in particular 3, under more dras tic conditions (70—80 C, 6—12 h) cleave the silatrane framework in 1 alkylsilatranes with the formation of IL of different structure: [R(OH)Si(OCH2CH2)2N +(H) CH2CH2OH]•[ OOCCH2OC6H4Me 2]. 15 Compounds 8, 10, and 11 are dense IL, 9, 12, and 13 are low melting powders. All of them are well soluble in water, alco hols, acetone, and chloroform. Their structures were confirmed by 1H and 13C NMR and IR spectroscopy, as well as by elemen tal analysis. IR spectra were recorded on a Varian 3100FT IR75 spectrophotometer, 1H and 13C NMR spectra (in CDCl3) were recorded on a DPX 400 spectrometer (1H, 400.13 MHz; 13C, 101.62 MHz; internal standard HMDS).