Non-covalent interactions between thio-caffeine derivatives and water-soluble porphyrin in ethanol-water environment Agnieszka Lipke a, ⁎, Magdalena Makarska-Bialokoz a , Arleta Sierakowska b , Beata Jasiewicz b a Department of Inorganic Chemistry, Maria Curie-Sklodowska University, M. C. Sklodowska Sq. 2, 20-031 Lublin, Poland b Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61-614 Poznań, Poland abstract article info Article history: Received 29 September 2017 Received in revised form 9 November 2017 Accepted 16 November 2017 Available online xxxx To determine the binding interactions and ability to form the non-covalent systems, the association process be- tween 5,10,15,20-tetrakis[4-(trimethylammonio)phenyl]-21H,23H-porphine tetra-p-tosylate (H 2 TTMePP) and a series of five structurally diverse thio-caffeine analogues has been studied in ethanol and ethanol-water solu- tions, analyzing its absorption and steady-state fluorescence spectra. The porphyrin fluorescence lifetimes in the systems studied were established as well. During the titration with thio-caffeine compounds the slight bathochromic effect and considerable hypochromicity of the porphyrin Soret band maximum can be noted. The fluorescence quenching effect observed for interactions in H 2 TTMePP - thio-caffeine derivative systems, as well as the order of binding and fluorescence quenching constants (of 10 5 –10 3 mol -1 ) suggest the existence of the mechanism of static quenching due to the formation of non-covalent and non-fluorescent stacking com- plexes. In all the systems studied the phenomenon of the fractional accessibility of the fluorophore for the quencher was observed as well. Additionally, the specific binding interactions, due to the changes in reaction en- vironment polarity, can be observed. It was found that thio-caffeine compounds can quench the porphyrin fluo- rescence according to the structure of thio-substituent in caffeine molecule. The obtained results can be potentially useful from scientific, therapeutic or environmental points of view. © 2017 Published by Elsevier B.V. Keywords: Thio-caffeine derivatives Water-soluble porphyrin Fluorescence quenching Non-covalent interactions 1. Introduction Caffeine (1,3,7-trimethylxanthine) is a naturally occurring xanthine derivative, which presents a wide spectrum of biological and medical applications [1–8]. As it was previously demonstrated, methylxanthines show the protective abilities towards the living cells and through the process of hetero-association, resulting in formation of stacking non-co- valent systems, are able to counteract the cytotoxic and mutagenic ef- fects of many aromatic compounds dangerous for humans [1–3,6,9– 15]. Stacking systems, generated between methylxanthines and e.g. ar- omatic groups of drugs, influence the concentration of free drug mole- cules available for the cells [9], what can be applied to diminish some side effects associated with the high local concentrations of these drugs in the initial phase of their administration [16–18]. It is well-known that caffeine has significant abilities to scavenge highly reactive free radicals and excited states of oxygen and protect cru- cial biological molecules against these species. It was also found that C8- substituted caffeine derivatives are adenosine receptor antagonists [19– 21], acetylcholinesterase inhibitors [22] and monoamine oxidase inhibitors [23–25], as well as anticancer agents [26]. Within this group the 8-thio-caffeine analogues belong to a pharmacologically important subclass [27–30]. The thio-caffeine derivatives were found to possess ex- ceptionally high antioxidant and cytoprotective properties, what predes- tines this class of compounds to act as effective antioxidants for preventing oxidative stress-induced diseases or artheriosclerosis [31]. Re- cently reported 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine pre- sents exceptionally high antioxidant properties and together with 6- thiocaffeine and 2,6-dithiocaffeine protects human erythrocytes against AAPH-induced oxidative damage [31]. Whereas water-soluble cationic porphyrins, the group of fluorescent macrocyclic compounds showing the specific spectroscopic and redox properties, can play the role of sensing materials to detect different, es- pecially biologically active substances, presented in aqueous environ- ment [1,6,32–40]. There are many studies concerning the binding interactions between xanthines and biologically active aromatic agents [3–5,8,41]. However, the binding interactions of thio-caffeine analogues with water-soluble porphyrins have not been studied as yet. Spectral analysis of such interactions could be particularly useful from a thera- peutic point of view, in identification of ligands with potential antican- cer activity [34] or in designing of new porphyrin-based sensors [42]. Therefore to determine the binding interactions and ability to form the non-covalent systems, the association process between 5,10,15,20- Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 192 (2018) 304–311 ⁎ Corresponding author. E-mail addresses: agnieszka.lipke@poczta.umcs.lublin.pl (A. Lipke), makarska@hektor.umcs.lublin.pl (M. Makarska-Bialokoz). https://doi.org/10.1016/j.saa.2017.11.038 1386-1425/© 2017 Published by Elsevier B.V. Contents lists available at ScienceDirect Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy journal homepage: www.elsevier.com/locate/saa