Synthesis of glucosamine-conjugated metal complexes for anticancer and anti-metastatic targeted therapy

Platinum and palladium complexes of the Schiff base of glucosamine and 8-hydroxy-2- quinolinecarboxaldehyde (OQN) were synthesized by the reaction of either Pt(DMSO)iCb or Na2PdCl4 in methanol with the ligand. Single crystal X-ray diffraction analysis revealed that these complexes form different dimeric structures with TI-TI stacking and metal-metal interactions in the solid states

A series of aminosugar-conjugated Schiff base complexes for anticancer therapy

Currently, platinum compounds are being used as the mainstay for many anticancer therapies despite the dose-limiting side effects, so there is a need to search for better candidate drugs having similar mechanism of action. Recently, palladium and platinum complexes 1 and 2 of a Schiff base ligand “Oqn”, composed of an aminosugar (such as glucosamine) and 8-hydroxy-2- quinolinecarboxaldehyde, were developed and show promising anticancer effectiveness, even against cisplatin-resistant cancer cell lines. Intracellular signal protein targeting by 1 and DNA strand breaks caused by 2 have been proposed as the mechanism for anticancer activity. In an effort to improve stability and to study the mechanism of action, we have also synthesized the galactosamine (3, 4) and the acetylated glucosamine analogs (5, 6, 7) of the abovementioned complexes. Interaction of the non-acetylated complexes 1, 2, 3, and 4 with bovine serum albumin were carried out by fluorescence-quenching assay and circular dichroism spectroscopy. When the glucosamine- containing Oqn complexes are dissolved in water, hydrolysis of the complex occurs rather rapidly. We have studied the rate of hydrolysis of complexes 1 and 2 in different aqueous solutions and determined the influence of pH and chloride concentration. Finally, we have synthesized possible hydrolysis products of the Pt- and Pd-Oqn (GlcN) complexes; both were characterized by X-ray crystallography and the hydrolysis product of Pd-Oqn (GlcN) was confirmed by 1 H NMR. We propose the mechanisms by which the hydrolysis occurs based on these findings

A silver(I) complex of acetylsinigrin: Structure and myrosinase-like activity

Background: In plants, glucosinolates such as sinigrin are decomposed into glucose and the aglycone by the enzyme myrosinase through cleavage of the glycosidic C-S bond. The aglycone can rearrange to the corresponding isothiocyanate which has a defensive function. The inorganic method historically used to cleave the C-S bond is through Ag(I), but the mechanism remains unknown. Methods: Acetylation of sinigrin yielded O-acetylsinigrin, which was then treated with Ag(I) triflate to yield the Ag(I) complex (Ag·SinAc) which was characterized by X-ray crystallography. The Ag(I)- induced cleavage of the glycosidic C-S bond was evaluated by 1 H NMR spectroscopy in both sinigrin and O-acetylsinigrin. Density functional theory (DFT) and natural bonding orbital (NBO) analyses were used to determine the mechanism of the C-S bond activation in putative solution-state structures. Results: The crystal structure of Ag·SinAc was successfully refined showing that the Ag(I) ion is bound to acetylsinigrin though the sulfated thiohydroximate and to its ethylene moiety by an organometallic Ag-(η2-C=C) bond. The presence of Ag(I) ions readily cleaves the C-S bond of sinigrin at room temperature. The same reaction requires heating in the case of Ag·SinAc. The Ag(I)-induced reaction is analogous to the action of myrosinase. Theoretical calculations show that the C-S bond activation is largely due to the polarizing effect of Ag(I) coordination to the S atom, and the stabilization of the leaving group. Conclusions: An unprecedented Ag(I) complex of a glucosinolate derivative has been synthesized and structurally characterized, which allowed the mechanistic elucidation of the myrosinase-like activity of the Ag(I) ion

Catalytic Enantioselective Reaction of 2<i>H</i>‑Azirines with Thiols Using Cinchona Alkaloid Sulfonamide Catalysts

The first catalytic enantioselective reaction of 2<i>H</i>-azirines with thiols has been developed. The obtained aziridines can be converted to optically active oxazolines, aziridylamides, or α-sulfonyl esters. Transformation of these optically active aziridines showed that 2<i>H</i>-azirines act as β,β-dicarbocationic amine synthons

Dinuclear Iron(0) Complexes of N‑Heterocyclic Carbenes

The synthesis, structures, and reactivity of dinuclear Fe⁰ complexes of N-heterocyclic carbenes (NHCs, denoted as L) are reported. The NHC adducts of ferric chloride (L)­FeCl₃ were prepared from the reactions of FeCl₃ with L in toluene. The reduction of (L)­FeCl₃ with KC₈ resulted in the formation of the dinuclear Fe⁰ complexes Fe₂{μ-η¹(C):η⁶(arene)-L}₂ (<b>2a</b>, L = 1,3-bis­(2,4,6-trimethylphenyl)­imidazol-2-ylidene (IMes); <b>2b</b>, L = 1,3-bis­(2,6-diisopropylphenyl)­imidazol-2-ylidene (IPr)), in which NHC ligands bridge two iron atoms using one of the arene rings as an η⁶ ligand. Their magnetic properties are different: <b>2a</b> is paramagnetic and <b>2b</b> is diamagnetic. The dinuclear complexes <b>2a</b>,<b>b</b> serve as precursors for monomeric (NHC)­Fe⁰ species, and treatment of <b>2a</b>,<b>b</b> with 1 atm of CO led to the formation of (L)­Fe­(CO)₄. Complex <b>2a</b> was found to react with 1-azidoadamantane, giving rise to the dinuclear tetrazene complex (IMes)­Fe­(μ-NAd)₂Fe­(AdNNNNAd) (<b>4</b>)

Complex formation of silver(I) ions with a glucosinolate derivative: Structural and mechanistic insights into myrosinase-mimicking C-S bond cleavage

The crystal structure of an unprecedented silver complex of O-acetylsinigrin has shown chelating bonds of the sulfated thiohydroximate and an η2-bond of the ethylene moiety with Ag(i). Mechanistic studies on the formation and decomposition of the complex by the 1H NMR measurements and theoretical calculations with the DFT method indicated relevance to the glucosinolate degradation in biological systems