Prospects of Metal Complexes Peripherally Substituted with Sugars in Biomedicinal Applications

Abstract

Metal complexes possess unique tunable properties, such as radioactivity, cytotoxicity or photophysical features, enabling them to act as diagnostic tracers or therapeutic agents. In applying them in biological systems, it is often necessary to enhance their solubility and biocompatibility. To achieve such goals, like the targeting of binding domains, transport systems and enzyme activities, the attachment of carbohydrate moieties appears to be suitable. Sugar-substitution in the periphery of metal complexes has therefore become a strongly growing field of research. Outlined herein is a selection of recent examples.

Glycoconjugate Probes and Targets for Molecular Imaging Using Magnetic Resonance

“…Chemically well-defined, mono disperse and characterized multivalent agents can be assembled by an alternative molecular design: the conjugation of dendrimeric-clustered carbohydrate bifunctional reagents through spacers to an MRI reporter group. Various Gd(III) complexes of the DTPA-and DOTA-type ligands, peripherally substituted with one or more targeting group(s) consisting of a clustered carbohydrate of variable valence, with different topologies (FiguRe 3), containing an increasing number of terminal galactosyl (Gal), lactosyl (Lac) or glycosyl (Glc) groups, have been synthesized and studied [31][32][33][34][35][36]. The ligands included various DOTA monoamide derivatives (FiguRe 4), with one (DOTAGal, DOTAGlc and DOTALac; 9), two (DOTAGal 2 , DOTAGlc 2 and DOTALac 2 ;10) or four (DOTAGal 4 ; 12) terminal sugar groups, one DOTA cis-bisamide derivative with two terminal sugar groups (DO2A(cis)Gal 2 ; 11) and DTPA bisamides with two (DTPAGal 2 and DTPALac 2 ; 13) or four (DTPAGal 4 ; 14) terminal sugar groups.…”

[(2R,3S)-Butane-1,2,3,4-tetraol-κ3O1,O2,O3](ethanol-κO)tris(nitrato-κ2O,O′)samarium(III)

“…carbohydrates (sugars) and metal ions may be involved in many biochemical processes (Gottschaldt & Schubert, 2009). …”

“…For background to the coordination behaviour of sugars to metal cations, see: Gottschaldt & Schubert (2009). For the crystal structure of free erythritol, see: Bekoe & Powell (1959).…”

Carbohydrate– N -heterocyclic carbene metal complexes: Synthesis, catalysis and biological studies

“…For the purposes of discovering novel classes of metal drugs, many carbohydrate ligands have been designed, synthesized and attached to different metal centres. There are many reviews [8][9][10][11] on this topic, including a detailed book chapter covering the research up to 2013 [62]. Despite a number of studies of NHC-metal complexes and carbohydrate-metal complexes in the bio-related research fields mentioned above, the medicinal properties of metal complexes containing both NHC ligands and carbohydrates are rarely discussed.…”

“…Thus, carbohydrates have been widely studied across many fields [8][9][10][11]. Methods for the synthesis of a variety of carbohydrate-functionalised alkyl halides, amines, azides and alkynes are well established and many of these compounds are readily available.…”