Metal-dithiocarbamate complexes: chemistry and biological activity

Abstract

Dithiocarbamates are highly versatile mono-anionic chelating ligands which form stable complexes with all the transition elements and also the majority of main group, lanthanide and actinide elements. They are easily prepared from primary or secondary amines and depending upon the nature of the cation can show good solubility in water or organic solvents. They are related to the thiuram disulfides by a one-electron redox process (followed by dimerisation via sulfur-sulfur bond formation) which is easily carried out upon addition of iodide or ferric salts. Dithiocarbamates are lipophilic and generally bind to metals in a symmetrical chelate fashion but examples of other coordination modes are known, the monodentate and anisobidentate modes being most prevalent. They are planar sterically non-demanding ligands which can be electronically tuned by judicious choice of substituents. They stabilize metals in a wide range of oxidation states, this being attributed to the existence of soft dithiocarbamate and hard thioureide resonance forms, the latter formally resulting from delocalization of the nitrogen lone pair onto the sulfurs, and consequently their complexes tend to have a rich electrochemistry. Tetraethyl thiuramdisulfide (disulfiram or antabuse) has been used as a drug since the 1950s but it is only recently that dithiocarbamate complexes have been explored within the medicinal domain. Over the past two decades anti-cancer activity has been noted for gold and copper complexes, technetium and copper complexes have been used in PET-imaging, dithiocarbamates have been used to treat acute cadmium poisoning and copper complexes also have been investigated as SOD inhibitors.

In vitro antibacterial and time kill evaluation of mononuclear phosphanegold(I) dithiocarbamates

“…The increasing interest in the antiproliferative activity of auranofin® builds upon investigations of a full range of gold (I) and gold(III) compounds [26][27][28], a good number of which contain the P-Au-S chromophore with thiolates such as mercaptopurinate [29][30][31], isomeric mercaptobenzoates [32,33], thiobenzoate [34] and, pertinent to the present investigation, 1,1-dithiolates such as dithiocarbamates and xanthates [35]. In keeping in with the wide range of biological activities exhibited by metal (incorporating transition and main group elements) dithiocarbamates [36], a relatively large number of studies have been conducted on phosphanegold(I) dithiocarbamates [37][38][39][40][41], including the determination of biological targets and mechanisms of cell death. Given the emerging interest in the antimicrobial activity of gold compounds [36] and the knowledge that certain metal dithiocarbamates exhibit anti-microbial activity [21], recently a series of phosphanegold(I) dithiocarbamates, namely R3PAu[S2CN(iPr)CH2CH2OH] for R = Et, Cy and Ph, were investigated for antimicrobial activity against a panel of 25 strains of Gram-positive and Gram-negative bacteria [42].…”

“…In keeping in with the wide range of biological activities exhibited by metal (incorporating transition and main group elements) dithiocarbamates [36], a relatively large number of studies have been conducted on phosphanegold(I) dithiocarbamates [37][38][39][40][41], including the determination of biological targets and mechanisms of cell death. Given the emerging interest in the antimicrobial activity of gold compounds [36] and the knowledge that certain metal dithiocarbamates exhibit anti-microbial activity [21], recently a series of phosphanegold(I) dithiocarbamates, namely R3PAu[S2CN(iPr)CH2CH2OH] for R = Et, Cy and Ph, were investigated for antimicrobial activity against a panel of 25 strains of Gram-positive and Gram-negative bacteria [42]. While the R = Et compound had broad range activity against both Gram-positive and Gram-negative bacteria, the R = Cy and Ph compounds exhibited specific activity against Gram-positive bacteria.…”

Bis(phosphane)copper(I) and silver(I) dithiocarbamates: crystallography and anti-microbial assay

“…The utility of a full range of transition metal and main group element dithiocarbamates as potential metal-based drugs has been reviewed recently [11]. Prominent amongst these are gold dithiocarbamates, including phosphane gold(I) dithiocarbamates.…”

Exploring the crystallization landscape of cadmium bis(N-hydroxyethyl, N-isopropyldithiocarbamate), Cd[S2CN(iPr)CH2CH2OH]2

“…medicinal [1] and as single source precursors for nanoparticle generation of chalcogenides [2], complement well established uses, e.g. as lubricants, in the vulcanization of rubber, as flotation agents, etc.…”