Vol.:(0123456789) 1 3 Chemical Papers https://doi.org/10.1007/s11696-018-0581-9 SHORT COMMUNICATION Impact of ligands structure on formation of hydrophilic colloids from their Gd(III) complexes with high magnetic relaxivity Alexey Stepanov 1  · Gulnaz Gimazetdinova 2  · Sofa Kleshnina 1  · Irek Nizameev 1,2  · Rustem Amirov 3  · Svetlana Solovieva 1  · Rinas Nagimov 2  · Alexandra Voloshina 1  · Anastasiya Sapunova 1  · Asiya Mustafna 1 Received: 6 April 2018 / Accepted: 25 August 2018 © Institute of Chemistry, Slovak Academy of Sciences 2018 Abstract The present paper introduces specifc structure of thiacalix[4]arenes derivatives adopting 1,3-alternate conformation with alkyl-carboxyl substituents as ligands for conversion of their complexes with Gd(III) ions into hydrophilic colloids with longitudinal (r 1 ) and transverse relaxivities (r 2 ) higher than that of Gd(III)-based commercial contrast agents (r 1 = 20.53 and r 2 = 23.46 mM −1  s −1 at 0.47 T). pH-dependent coordination of Gd(III) ions via carboxyl substituents of the thiacalix[4]arenes is the driving force for the complex formation, while the precipitation of the complexes is the basis for the colloids formation. Tert-butyl and butyl substituents of thiacalix[4]arenes were found to be of crucial impact on the complex precipitation. The specifc inner- and outer-sphere ligand environment provided by the thiacalix[4]arene ligands was revealed as the optimal for high r 1 and r 2 values of the colloids. High relaxivities along with negligible cytotoxicity open up the possibility of their further use as positive contrast agents in magnetic resonance imaging (MRI). Keywords Carboxylated thiacalix[4]arenes · Longitudinal relaxivity · Paramagnetic colloids · Hydrophilic colloids · Gd(III) ions Introduction Gd(III) chelate complexes have attracted considerable atten- tion of researches in recent decades owing to their appli- cation as contrast agents in magnetic resonance imaging (MRI) (Carniato et al. 2010; Rohrer et al. 2005; Stepanov et al. 2017; Caille et al. 2012). At present molecular Gd(III) chelates such as Magnevist, Dotarem, Gadovist, etc., are the positive contrast agents approved by FDA for clini- cal MRI procedures, while their drawbacks are also well known (Rohrer et al. 2005). For example, they still raise toxicity issues, their blood circulation time is not high enough and they provide only moderate contrasting efect since longitudinal relaxivities of such complexes are not high (3–8 mM −1  s −1 ). The above-mentioned disadvantages of molecular MRI contrast agents have led to the develop- ment of nanoparticulate contrast agents in which Gd(III)- based water-insoluble oxides (Zhou et al. 2014; Majeed and Shivashankar 2014; Bridot et al. 2007; Park et al. 2009; Luo et al. 2013; Cho et al. 2014), salts (Na et al. 2007; Hifumi et al. 2006; Evanics et al. 2006; Rodriguez-Liviano et al. 2013) or complexes (Aime et al. 1996; Morcos 2008) sta- bilized with water-soluble biocompatible organic layers provide better positive contrast enhancement and negligible cytotoxicity. It is important to stress out that some struc- tural features necessary for high longitudinal relaxivities of Gd(III)-based nanoparticles have already been reported, namely impeded rotation of Gd(III) centres due to their aggregation into the nanoparticles. The efcient hydration of the Gd(III) centres is another necessary feature for high magnetic relaxivity, which, in turn, can be obtained for small nanoparticles (about 2–5 nm) (Stepanov et al. 2017; Reiter et al. 2006; Pereira et al. 2010; Carne-Sanchez et al. 2013). Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11696-018-0581-9) contains supplementary material, which is available to authorized users. * Alexey Stepanov aleksestepanov@yandex.ru 1 Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientifc Center of RAS, Arbuzov Str., 8, Kazan 420008, Russia 2 Kazan National Research Technological University, Kazan 420015, Russia 3 Kazan (Volga Region) Federal University, Kremlyovskaya Str., 18, Kazan 420008, Russia