Methyl 5′-Chloro-8-formyl-5-hydroxy-1′,3′,3′-trimethyl-spiro-[chromene-2,2′-indoline]-6-carboxylate

Spiropyrans modified with reactive polyfunctional substituents are of great interest as building blocks for the creation of various smart systems with controllable properties for materials science and biomedicine. In this study, a new highly modified spiropyran of the indoline series, methyl 5′-chloro-8-formyl-5-hydroxy-1′,3′,3′-trimethyl-spiro[chromene-2,2′-indoline]-6-carboxylate, was obtained via the cyclocondensation reaction from 5-chloro-1,2,3,3-tetramethyl-3H-indolium perchlorate and methyl 3,5-diformyl-2,4-dihydroxy-benzoate. The molecular structure of the target compound was confirmed by 1H, 13C NMR, and IR spectroscopy, as well as LC/MS and elemental analysis. Photochemical studies revealed photochromic activity for the obtained spiropyran at room temperature. The photoinduced merocyanine form demonstrated an enhanced lifetime and fluorescent properties in the red region of the spectrum

Novel Indoline Spiropyrans Based on Human Hormones β-Estradiol and Estrone: Synthesis, Structure, Chromogenic and Cytotoxic Properties

The introduction of a switchable function into the structure of a bioactive compound can endow it with unique capabilities for regulating biological activity under the influence of various types of external stimuli, which makes such hybrid compounds promising objects for photopharmacology, targeted drug delivery and bio-imaging. This work is devoted to the synthesis and study of new spirocyclic derivatives of important human hormones—β-estradiol and estrone—possessing a wide range of biological activities. The obtained hybrid compounds represent an indoline spiropyrans family, a widely known class of organic photochromic compounds. The structure of the compounds was confirmed by 1H and 13C NMR, IR, HRMS and single-crystal X-ray analysis. The intermolecular interactions in the crystals of spiropyran (3) were defined by Hirshfeld surfaces and 2D fingerprint plots, which were successfully acquired from CrystalExplorer (v21.5). All target hybrids demonstrated pronounced activity in the visible region of the spectrum. The mechanisms of thermal isomerization processes of spiropyrans and their protonated merocyanine forms were studied by DFT methods, which revealed the energetic advantage of the protonation process with the formation of a β-cisoid CCCH conformer at the first stage and its further isomerization to more stable β-transoid forms. The proposed mechanism of acidochromic transformation was confirmed by the additional NMR study data that allowed for the detecting of the intermediate CCCH isomer. The study of the short-term cytotoxicity of new spirocyclic derivatives of estrogens and their 2-formyl-precursors was performed on the HeLa cell model. The precursors and spiropyrans differed in toxicity, suggesting their variable applicability in novel anti-cancer technologies

Reaction of quinaldine with 4,6-di(tert-butyl)-3-nitro-1,2-benzoquinone. Dependence of the outcome on the reaction conditions and a deeper insight into the mechanism

Condensation of quinaldine with 4,6-di (tert-butyl)-3-nitro-1,2-benzoquinone results in the formation of 5,7-di (tert-butyl)-2-(quinoline-2-yl)-1,3-tropolone, 5,7-di (tert-butyl)-4-nitro-2-(quinoline-2-yl)-1,3-tropolone, 3,3-dimethyl-2-(5-hydroxy-4-nitro-3-tert-butyl-6-quinoline-2-yl-pyridine-2-yl)butanoic acid, 6-(2,2-dimethylprop-3-yl)-5-tert-butyl-4-nitro-2-(quinoline-2-yl)-pyridine-3-ol, 1,7-di (tert-butyl)-3-(quinoline-2-yl)-2-azabicyclo-[3.3.0]octa-2,7-diene-4,6-dione-N-oxide. The formation of 1,3-tropolone and pyridine-2-yl butanoic acid derivatives proceeds through a ring expansion and 2-azabicyclo [3.3.0]octa-2,7-diene-4,6-dione-N-oxide via the contraction of the o-quinone ring. The structure of the heterocyclic compounds obtained was justified by X-ray diffraction analysis, NMR spectroscopy, IR- and HRMS-spectrometry, and the proposed mechanisms of their formation include the participation of an intermediate product of the expansion reaction of the o-quinone cycle - 5,7-di (tert-butyl)-4-nitro-2-(quinoline-2-yl)-cyclohepta-1,3,5-triene-1,3-diol, which was first isolated preparatively. The DFT/B3LYP/6–311++G** methods were used to determine the thermodynamic stability of tautomeric forms of intermediate products, as well as the relative stability of NH and OH tautomers of 5,7-di (tert-butyl)-2-(quinolin-2-yl)-1,3-tropolone and 5,7-di (tert-butyl)-4-nitro-2-(quinolin-2-yl)-1,3-tropolone