Alkyl-malonate-substituted thiacalix[4]arenes as ligands for bottom-up design of paramagnetic Gd(III)-containing colloids with low cytotoxicity

• Published in: Arabian journal of chemistry 2020-01, Vol.13 (1), p.453-463
• Main Authors: Stepanov, Alexey, Nizameev, Irek, Amirov, Rustem, Kleshnina, Sofia, Khakimullina, Gulshat, Solovieva, Svetlana, Voloshina, Alexandra, Strobykina, Anastasya, Gubaidullin, Aidar, Nugmanov, Ramil, Mustafina, Asiya
• Format: Article
• Language: English
• Subjects: Cytotoxicity; Gd(III) ions; Hydrophilic colloids; Longitudinal relaxivity; Malonate thiacalixarenes; Paramagnetic colloids
• ISSN: 1878-5352; 1878-5379
• DOI: 10.1016/j.arabjc.2017.05.017

The present work introduces thiacalix[4]arene adopting 1,3-alternate conformation with alkyl-malonate terminal substituents as ligands for Gd(III) ions. pH-dependent complex formation of Gd(III) ions via alkyl-malonate substituents in aqueous DMSO solutions results in a precipitation. The precipitated complexes were converted into hydrophilic colloids of “plum-pudding” morphology, where the Gd(III) complexes form hard small (1.5–4nm) cores included into larger (about 180nm) soft PSS shells. The precipitate-to-colloid transformation is facilitated by polystyrolsulfonate (PSS) for Gd(III) complexes with thiacalix[4]arene bearing propyl-malonate groups, while the presence of PSS triggers a dissolution of the precipitated complexes for thiacalix[4]arenes with pentyl-malonate substituents. To a lesser extent the similar tendency disturbs the formation of PSS-stabilized colloids on the basis of butyl-malonate substituted thiacalix[4]arene. The PSS-stabilized colloids exhibit high longitudinal and transverse relaxivities (r1=23.8 and r2=29.4mM−1s−1 at 0.47T, respectively), while the recoating of the PSS-stabilized colloids with polyethyleneimine is accompanied by the dissolution of the hard cores. High relaxivity along with low cytotoxicity of PSS-stabilized colloids indicates their applicability as contrast agents in MRI.