Metals in Medicine: Therapeutic Agents

Abstract

Within the emerging field of medicinal inorganic chemistry, the realization that metal complexes can be designed as both therapeutic and diagnostic agents with novel mechanisms of action is increasing. Some recent advances are highlighted in this review, beginning with the success of platinum anticancer complexes and attempts to extend such activity to other transition metals, even to arsenic. Lithium is widely used for bipolar affective disorders, and gold is used for the treatment of rheumatoid arthritis. Metal ions also play crucial roles in contrast agents for magnetic resonance imaging and in radiopharmaceuticals used for imaging and therapy. Metal complexes offer flexible design platforms as enzyme inhibitors, and metals in enzyme active sites can be key drug targets. The antimicrobial and antiviral activities of certain metal complexes may prove useful in the fight against antibiotic resistance. Metals play key roles, too, in the control of small signaling molecules such as nitric oxide and carbon monoxide. Control of the uptake and distribution of the essential metals also presents a challenge, which is aided by modern genomic knowledge.

Modulating In Vitro Photodynamic Activities of Copper(II) Complexes

“…[1][2][3][4][5] Systemic side effects in chemotherapy due to highdose requirements and tumor nonspecificity have caused serious concerns, leading to a search for a cost-effective, more tolerable, and tumor-specific treatment modality for cancer. [1][2][3][4][5] Systemic side effects in chemotherapy due to highdose requirements and tumor nonspecificity have caused serious concerns, leading to a search for a cost-effective, more tolerable, and tumor-specific treatment modality for cancer.…”

Crystal structure of dichloro(N,N-dimethylpyridin-4-amine)- (η6-p-cymene)ruthenium(II), RuCl2(C7H10N2)(C10H14)

“…Arene ruthenium compounds as anticanceragents had first been introduced by Tocher et al in 1992 [2], who had observed acytotoxicity enhancement by coordinating the anticancer agent metronidazole (1-b-hydroxyethyl-2-methyl-5-nitroimidazole) to ab enzene ruthenium dichloro fragment, stimulating the search for organometallic anticancer drugs [3][4][5].The accelerating pace of reported applications for DMAP (N,Ndimethylpyridin-4-amine) and the availability of DMAP in commercial quantities at modest prices hasc ontinued to stimulate great interest in its useasacatalyst in the fields of organic, polymer, analytical and biochemistry [6]. It has ar elatively high toxicity andisparticularlydangerous becauseofits abilitytobe absorbedthrough theskin [7].Inorder to developnew synergistic anticancer drugs, we trytocoordinateDMAPtothe arene-ruthenium half-sandwich "piano-stool"u nitw hich is an excellent scaffold forthe coupling of organicsegments for targeted chemotherapy [8]. The title complex adopts at ypical "three-legged piano-stool" configuration with the tetrahedral arrangement of the p-cymene andthe otherthree ligands(DMAP boundvia nitrogen atom,and twochloridoligands)about them etal center ruthenium.The pcymene ring is planar with mean deviation of 0.005(4) Å, the pyridylring is also planar with mean deviation of 0.003 (4) …”

100 years of metal coordination chemistry: from Alfred Werner to anticancer metallodrugs

“…[6][7][8][9] In the following sections, we will restrict the discussion to examples of precious metal anticancer drug candidates based on Pt, Ru, Os, and Ir. …”

“…Octahedral low-spin 5d 6 Pt IV complexes are well known to be relatively inert towards ligand substitution, but can be activated chemically by reduction. [29][30][31] They are less susceptible to substitution reactions than square-planar platinum(II) complexes and so as drugs are likely to undergo fewer reactions en route to the tumour.…”

“…88,89 Interestingly, the first article written by Werner on ruthenium complexes was part of his series "Zur Theorie der Hydrolyse" published in 1907, 16 Promising also as anticancer agents are organometallic half-sandwich 'piano-stool' Ir III complexes. 97 Somewhat surprisingly, low-spin 5d 6 Ir III complexes can be quite labile and readily exchange ligands. Ir III is not readily stabilized by arenes but is stabilized by cyclopentadienyl ligands, and especially by pentamethylcyclopentadienyl.…”