Abstract
Modern synthetic inorganic and organometallic chemistry is constantly exploring uncharted chemical space to identify promising candidates for medicinal and catalytic applications. Key criteria of such candidates are easy accessibility, thermodynamic and/or physiological stability and compatibility with water for medicinal applications. [Re(n6-arene)2]+ complexes fulfill all these prerequisites. Notably, their strong electron-withdrawing effect, owing to the positively charged scaffold, forms the central theme of this thesis—a systematic exploration of the electronic impact of the [Re(h6-arene)2]+ motif on the catalytic and biological activities of corresponding functional attachments. Covalent conjugates between [Re(n6-aniline)(n6-C6H6)]+ or [Re(n6-aniline)2]+ and terpyridine (terpy) were chosen as model for such exploration due to straightforward synthesis of the individual sub-units and an established track record in catalytic and biological applications of the terpy ligand. Linking the two sub-units between the 4’-position in terpy and the aniline nitrogen atoms afforded the [Re(n6- aniline-4’-terpy)(n6-C6H6)]+ (RcTerpy) and [Re(n6-aniline-4’-terpy)2]+ (RcTerpy2) chelators Resulting [M(RcTerpy)2] (M = FeII, CoII/III and NiII) complexes are isostructural to the parent [M(Terpy)2]2/3+ complexes. Nickel and cobalt derivatives demonstrated electrocatalytic reduction of water to di-hydrogen in cyclic voltammetry analyses. In photocatalytic water reductions, [Co(RcTerpy)2]5+ showed increased turnover numbers (>4000 H2/Co) compared to analogous complexes with 4’-aniline substituents (>3400 H2/Co). Similarly, the catalytic activity in water-based hydrogen transfer reactions for the conversion of nitroarenes to the respective anilines with [Rh(RcTerpy)Cl3] complexes compared well to regular [Rh(terpy)Cl3] catalysts with similar substrate scope and reaction rates. The same chelators delivered interesting anticancer drug candidates by coordinating CuCl2 to RcTerpy and RcTerpy2. Both, the ligands and resulting complexes, were cytotoxic in vitro against cancer cell lines (HT29, A459) and exerted higher potency than the reference compound Cisplatin with IC50 values as low as 1 uM. Mitochondrial respiration suppression was identified as a possible mode of action for this class of compounds as they suppressed cellular oxygen consumption rates. Crucially, the [Re(h6- arene)2]+ scaffolds provided water solubility of the otherwise insoluble [Cu(terpy)Cl2] complexes. Furthermore, a theranostic approach may be possible with the presented system, as the 99mTc homlog of RcTerpy2 was also prepared; the technetium part acting as diagnostic tool via its radiopharmaceutical properties and the rhenium domain serving as a basis for treatment. The RcTerpy and RcTerpy2 chelators were thus proven as an attractive platform to investigate biological and catalytic activities of meridional tridentate chelated transition metal complexes. For this purpose, the otherwise strongly electron withdrawing effects of [Re(n6-arene)2]+ scaffold were largely rescinded by the amine linkers. The electronic influence of [Re(n6-arene)2]+ on (benz)imidazole-based N-hetero cyclic carbenes (NHC) attached directly via the imidazolium nitrogen, belonged next to the general topic. Absence of a linking unit between the arenes of [Re(n6-arene)2]+ and the NHCs reduced their sigma-donating abilities. As a consequence, resulting [Au(NHC)I] complexes showed tenfold slower lactonization of alkynoic acids compared to the parent catalysts without a [Re(n6-arene)2]+ motif. This behavior underlines the necessity of a rational modulation of the electronic properties of [Re(n6-arene)2]+ via attached functionalities. Further investigation of fundamental rhenium bis-arene chemistry delivered novel isoindoline bridged ansa[3]arenophanes of [M(n6-arene)2]+ (M = Re, 99mTc). They were prepared from the condensation between 1,2-dialdehydes and [M(n6-aniline)2]+. To the best of our knowledge, this is the first synthesis of a 99mTc ansa-complex. In addition to intramolecular ansa-complex formation, intermolecular reactivities formed two distinct dinuclear species of which one existed as a racemate of the axially chiral (P)- and (M)- enantiomers. A separate project constituted the synthesis, evaluation of photophysical properties and photocatalytic CO2 to CO reductions of fac-[Re(CO)3(diimine)Br] complexes with 3,3’-nitrogen bis- substituted bipyridyl chelators. The 3,3’-substitution motif directly modulated absorbance- and emission wavelengths and excited state lifetimes of their fac-{Re(CO)3}+ complexes. Bridging the 3,3’- positions with an urea or thiourea motif led to complexes with particularly long-lived phosphorescence emissions in the green part of the visible spectrum (lamdaem = 640-660 nm, pi = 75−80 ns). Consequently, we present a novel and facile synthetic methodology to tailor the photophysical properties of fac- [Re(CO)3(diimine)Br] complexes. Finally, 3,3’-diamino and diazaphenanthrene complexes were applied as photocatalysts in the reduction of CO2 to CO with turnover numbers reaching 300 CO/catalyst.
Csucker, Joshua