Diversity in the Interaction of Amino Acid- and Peptide-Based Hydroxamic Acids with Some Platinum Group Metals in Solution

Abstract

Complexes that incorporate both ligand(s) and metal(s) exhibiting cytotoxic activity can especially be interesting to develop multifunctional drug molecules with desired activities. In this review, the limited number of solution results collected in our laboratory on the complexes of Pd(II) and two other platinum group metals—the half-sandwich type, [(η6-p-cym)Ru(H2O)3]2+, and [(η5-Cp*)Rh(H2O)3]2+—with hydroxamic acid derivatives of three amino acids, two imidazole analogues, and four small peptides are summarized and evaluated. Unlike the limited number of coordination sites of these metal ions (four and three for Pd(II) and the organometallic cations, respectively), the ligands discussed here offer a relatively high number of donor atoms as well as variation in their position within the ligands, resulting in a large versatility of the likely coordination modes. The review, besides presenting the solution equilibrium results, also discusses the main factors, such as (N,N) versus (O,O) chelate; size of chelate; amino-N versus imidazole-N; primary versus secondary hydroxamic function; differences between hydrolytic ability of the metal ions studied; and hydrolysis of the coordinated peptide hydroxamic acids in their Pd(II) complexes, which all determine the coordination modes present in the complexes formed in measurable concentrations in these systems. The options for the quantitative evaluation of metal binding effectivity and selectivity of the various ligands and the comparison with each other by using solution equilibrium data are also discussed.

Nanostructured Gelatin Aerogel for Selective Recovery of Aqueous Pd(II) Based on Coordination to the Peptide Backbone

“…The bands at 1330, 1230, and 3283 cm –1 are associated with the N–H section of the amide bonds, while the one at 1631 cm –1 is associated with the CO moiety of the amide bonds of the gelatin backbone. The dramatic loss of peak intensity in the Pd­(II) equilibrated aerogel points out the strong and direct interaction of the metal ions with the amide bonds. ,, Palladium­(II) is well-known to form stable complexes with the amide moieties of peptides, which often induces the deprotonation and the coordination of the amide nitrogen even at highly acidic pH. − The Pd­(II) complex with the ionized amide nitrogens in the XG aerogels is most probably stabilized by the additional coordination of the adjacent carbonyl oxygens of the amides, as shown in Scheme . , The FT-IR results together with the demonstrated reversibility of the Pd­(II) binding suggest that the operative sorption mechanism is surface complexation. , …”

Design, Synthesis, and Biological Evaluation of Novel Hydroxamic Acid-Based Organoselenium Hybrids

“…The minimal inhibition dose causing death to 50% of cells was also estimated and is presented in Table 1 . The corresponding therapeutic indices (TI) are described as the proportion of the WI38 cells IC 50 to the IC 50 of the cancer cell (e.g., MCF-7 and HepG2) ( Table 1 ) [ 10 , 11 , 12 , 13 ].…”

“…Thus, the chelating propriety of hydroxamic acids with metal ions gives them the ability to interact with several metal-containing enzymes, with vast arrays of biological activities. Their solid chelating ability has been employed in metalloenzyme (e.g., Figure 2 ) [ 10 ] inhibition [ 11 ] via a metal binding group with an active site (i.e., HDAC, MMP, urease, lipoxygenase, angiostatin) ( Figure 2 ) [ 12 , 13 ]. Furthermore, this chelating ability has been employed in environmental remediation treatments and organic synthesis methods [ 14 ].…”