A set of styrylpyridinium (SP) compounds was synthesised in order to study their spectroscopic and cell labelling properties. The compounds comprised different electron donating parts (julolidine, p-dimethylaminophenyl, p-methoxyphenyl, 3,4,5-trimethoxyphenyl), conjugated linkers (vinyl, divinyl), and an electron-withdrawing N-alkylpyridinium part. Geminal or bis-compounds incorporating two styrylpyridinium (bis-SP) moieties at the 1,3-trimethylene unit were synthesised. Compounds comprising a divinyl linker and powerful electron-donating julolidine donor parts possessed intensive fluorescence in the near-infrared region (maximum at ~760 nm). The compounds had rather high cytotoxicity towards the cancerous cell lines HT-1080 and MH-22A; at the same time, basal cytotoxicity towards the NIH3T3 fibroblast cell line ranged from toxic to harmful. SP compound 6e had IC₅₀ values of 1.0 ± 0.03 µg/mL to the cell line HT-1080 and 0.4 µg/mL to MH-22A; however, the basal toxicity LD₅₀ was 477 mg/kg (harmful). The compounds showed large Stokes’ shifts, including 195 nm for 6a,b, 240 nm for 6e, and 325 and 352 nm for 6d and 6c, respectively. The highest photoluminescence quantum yield (PLQY) values were observed for 6a,b, which were 15.1 and 12.2%, respectively. The PLQY values for the SP derivatives 6d,e (those with a julolidinyl moiety) were 0.5 and 0.7%, respectively. Cell staining with compound 6e revealed a strong fluorescent signal localised in the cell cytoplasm, whereas the cell nuclei were not stained. SP compound 6e possessed self-assembling properties and formed liposomes with an average diameter of 118 nm. The obtained novel data on near-infrared fluorescent probes could be useful for the development of biocompatible dyes for biomedical applications.

Synthesis of a double-charged cationic amphiphilic 1,4-dihydropyridine derivative with dodecyl ester groups at positions 3 and 5 of the 1,4-DHP ring was performed starting from Hantzsch type cyclization of dodecyl acetoacetate, 2-naphthaldehyde and ammonium acetate. Bromination of this compound followed by nucleophilic substitution of bromine with (E)-4-(2-(naphthalen-2-yl)vinyl)pyridine gave the desired cationic amphiphilic 1,1′-{[3,5-bis(dodecyloxycarbonyl)-4-(naphthalen-2-yl)-1,4-dihydropyridine-2,6-diyl]bis(methylene)}bis{4-[(E)-2-(naphthalen-2-yl)vinyl]pyridin-1-ium}dibromide. The obtained target compound was fully characterized by IR, UV, ¹H-NMR, ¹³C-NMR, HRMS and microanalysis. The characterization of the cationic 1,4-DHP nanoparticles in an aqueous solution was performed by DLS measurements. The obtained results showed that the compound formed nanoparticles with an average diameter of around 300 nm, a PDI value of around 490 and a zeta-potential of around 20 mV for freshly prepared samples. However, after one week of storage at room temperature, an aggregation of nanoparticles was detected.

A series of new 3,5-difluoro-2-methylene-4-aryl-2,3,4,5-tetrahydropyridines were synthesised via the reaction of 1,4-dihydropyridines (1,4-DHPs) with in situ generated N-fluoro quinine through one-step transfer-fluorination using Selectfluor®. Halogenation of these tetrahydropyridines with N-chloro-(or bromo)succinimide yielded 2-(chloromethylene)-2,3,4,5-tetrahydropyridine-3,5-dicarboxylates 7a or 2-(bromomethylene) derivatives 7b,c. Palladium-catalysed oxidative Heck reaction of 2-methylenetetrahydropyridine 2d with phenylboronic acid (11a) afforded new fluorinated phenyl-substituted alkene 13a, while pyridyl-substituted alkenes 13b,c were synthesised via Suzuki cross-coupling of brominated derivatives 7b,c with 4-pyridinylboronic acid (11c) or 4-pyridineboronic acid pinacol ester (11d). Quaternisation of the pyridine moiety of dialkyl 3,5-difluoro-6-methyl-4-phenyl-2-(pyridin-4-ylmethylene)-2,3,4,5-tetrahydropyridine-3,5-dicarboxylates 13b,c produced pyridium derivatives 14a–c, 15a–c with pyridinium moieties bearing alkyl chains of varying lengths. These quaternised pyridine derivatives demonstrated the ability to form liposomes. The resulting liposomes prepared using the injection method had average particle sizes of 61–199 nm with polydispersity index (PDI) values of 0.17–0.56 one day after preparation, 65–306 nm with PDI values of 0.16–0.54 after four days, and 62–253 nm with PDI values of 0.17–0.47 after seven days. The zeta potential (ζ-potential) of the liposomes ranged from 5.5 to 51.6 mV. Stable nanoparticles were consistently formed by compounds containing at least one dodecyl alkyl chain. This study demonstrates that quaternised pyridinium derivatives can form stable nano-liposomal carriers with tunable sizes and ζ-potentials exceeding +30 mV, ensuring colloidal stability.

One of the most important steps in the synthesis of 1,4-dihydropyridine (1,4-DHP) amphiphiles is the bromination of methyl groups in positions 2 and 6 of the entire ring. However, up to now, only N-bromosuccinimide was mainly used for bromination 1,4-DHPs. In this work, the synthesis of bis-1,4-DHP derivatives with ethyl and dodecyl ester groups attached to 1,4-DHP ring at positions 3 and 5 was performed by Hantzsch synthesis. The experimental studies were carried out to find out the best conditions and the agent for the tetra bromination of bis-1,4-DHP methyl groups at positions 2 and 6. Four different brominating agents were screened. The use of pyridinium bromide–perbromide in ethyl acetate was found to be optimal for the bromination of methyl groups. The bromination reaction was followed by the synthesis of cationic pyridine moiety containing amphiphilic bis-1,4-DHP derivatives. By nucleophilic substitution of bromine with various substituted pyridines, 12 new amphiphilic bis-1,4-DHP derivatives were obtained. Evaluation of self-assembling properties of tetracationic bis-1,4-dihydropyridine derivatives by dynamic light scattering (DLS) measurements was also performed.