Herein, we present the synthesis and structural analysis of metal complexes of enantiomerically pure 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraazidoethylacetic acid (DOTAZA). DOTAZA is a new tunable analog of DOTA, a clinically approved chelator for various pharmaceutically relevant metal ions. In this work, we investigate the complexation chemistry of DOTAZA and report the crystal structures of a number of complexes with pharmaceutically relevant metal ions such as Gd³⁺ [magnetic resonance imaging (MRI)], Eu³⁺ (luminescence spectroscopy), Y³⁺ [positron emission tomography (PET)], In³⁺ [single-photon-emission computed tomography (SPECT)], and Na⁺. These structures provide useful information for imaging applications and demonstrate the potential of DOTAZA to form stable complexes. Owing to its clickable azide functionalities, it may be used for the development of tailored imaging reagents that retain the positive complexation chemistry of the parent compound DOTA.

Lectin–carbohydrate interactions are important for many biological processes of high pharmaceutical interest. Multivalent carbohydrate conjugates (glycoclusters) have been frequently used to study and manipulate these interactions. In this report, we present the synthesis of trimeric glucose and mannose conjugates that have been assembled with an AB₃ scaffold based on adamantane. Several neoglycoconjugates bearing three carbohydrates have been synthesized with different ethylene glycol spacers between the sugar moieties and the adamantyl core. An additional orthogonal functionality at the remaining adamantane bridgehead position allows the conjugation of these trimeric cluster glycosides to other functional molecules such as fluorescent dyes or a solid support for the construction of glycoarrays. We have evaluated the binding properties of trivalent carbohydrate derivatives to ConA as a model lectin in solution by STD-NMR and on a lectin array by using fluorescent glycoconjugates.

Herein, we report the synthesis of two enantiomeric DOTAZA esters and a related DOT3AZA ester. These compounds are tunable analogues of the well-known chelator DOTA and can be easily functionalized through click chemistry of the side-chain azide groups. Like DOTA, DOTAZA forms complexes with various di- and trivalent metals, as demonstrated in the synthesis and structural analysis of CuDOTAZA and the preparation of GdDOTAZA.

Carbohydrates are involved in a wide range of biological processes of pharmaceutical relevance. The selective recognition of carbohydrates is therefore of great interest in biology and medicine. In this study we present the synthesis of fluorescent multimeric benzoboroxoles and the analysis of multivalent binding processes to immobilized carbohydrate arrays by fluorescence spectroscopy. We observed high binding affinities of trimeric benzoboroxoles by determination of K_Dsurf values for their interaction with α-Gal on glass chips. The observed K_Dsurf values were in the mid-nM range (49 and 104 nM) and are comparable to the K_Dsurf values for binding of natural lectins, such as that of ConA to immobilized α-Man (79 nM). The array technology was found to be an excellent tool for studying the binding processes of multivalent lectin mimetics with respect to profiling and quantitation.

Benzoboroxoles are known to bind 1,2-diol motifs in carbohydrates in an aqueous environment. Their binding properties have been shown to be dependent on additional recognition sites such as peptides and the number of binding epitopes. In this paper we describe the synthesis of trimeric benzoboroxoles based on a rigid adamantyl core structure. The conjugates are assembled using copper-catalyzed click reactions of azide scaffolds with alkynyl-functionalized benzoboroxoles. The design of our trimeric benzoboroxoles followed a biomimetic principle and imitates the trimeric structure of some natural carbohydrate binding proteins (lectins). With an assortment of appropriately functionalized (3 + 1) adamantane scaffolds, trimeric benzoboroxoles have been generated which were combined with additional functional molecules such as dyes and peptides. In summary, we report a highly effective synthetic approach to modular trimeric boronolectines for the assembly of carbohydrate sensors.