Styrylpyridinium Derivatives for Fluorescent Cell Imaging

• Main Authors: Reinis Putralis (Author), Ksenija Korotkaja (Author), Martins Kaukulis (Author), Zhanna Rudevica (Author), Juris Jansons (Author), Olga Nilova (Author), Martins Rucins (Author), Laura Krasnova (Author), Ilona Domracheva (Author), Mara Plotniece (Author), Karlis Pajuste (Author), Arkadij Sobolev (Author), Felikss Rumnieks (Author), Laura Bekere (Author), Anna Zajakina (Author), Aiva Plotniece (Author), Gunars Duburs (Author)
• Format: Book
• Published: MDPI AG, 2023-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/ph16091245; 1424-8247
• Keywords: styrylpyridines; julolidine; self-assembly; near-infrared fluorescent dye; cell labelling; macrophages; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 16, Iss 9, p 1245 (2023)

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, <i>p</i>-dimethylaminophenyl, <i>p</i>-methoxyphenyl, 3,4,5-trimethoxyphenyl), conjugated linkers (vinyl, divinyl), and an electron-withdrawing <i>N</i>-alkylpyridinium part. Geminal or <i>bis</i>-compounds incorporating two styrylpyridinium (<i>bis</i>-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 <b>6e</b> 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 <b>6a</b>,<b>b</b>, 240 nm for <b>6e</b>, and 325 and 352 nm for <b>6d</b> and <b>6c</b>, respectively. The highest photoluminescence quantum yield (PLQY) values were observed for <b>6a</b>,<b>b</b>, which were 15.1 and 12.2%, respectively. The PLQY values for the SP derivatives <b>6d</b>,<b>e</b> (those with a julolidinyl moiety) were 0.5 and 0.7%, respectively. Cell staining with compound <b>6e</b> revealed a strong fluorescent signal localised in the cell cytoplasm, whereas the cell nuclei were not stained. SP compound <b>6e</b> 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.