Transition metal ions antibiotics

Many organic and inorganic compounds, fibers, and particles are capable of damaging nucleic acids by generating reactive oxygen species via the reduction of dioxygen. These stimuli include different classes of organic compounds, classic prooxidants (anticancer antibiotics, various quinones, asbestos fibers, and so on), and even antioxidants, which can be oxidized in the presence of transition metal ions. 

Transition metal ions cause a dramatic increase in the rate of hydrolysis of /Madam antibiotics [75][133][134], For example, copper(II) and zinc(II) ions increase the rate of alkaline hydrolysis ca. 108-fold and 104-fold, respectively [76], It has been suggested that the metal ion coordinates with both the carboxylate group and the /3-lactam N-atom of penicillins (A, Fig. 5.20). This complex stabilizes the tetrahedral intermediate and, thus, facilitates cleavage of the C-N bond catalyzed by the HO ion [74] [75], Such a model appears applicable also to clavulanic acid, imipenem, and monobactams, but it re-... 

Fig. 5.20. Modes of coordination of transition metal ions with /3-lactam antibiotics. Complex A In penicillins, the metal ion coordinates with the carboxylate group and the /3-lactam N-atom. This complex stabilizes the tetrahedral intermediate and facilitates the attack of HO-ions from the bulk solution. Complex B In benzylpenicillin Cu11 binds to the deprotonated N-atom of the amide side chain. The hydrolysis involves an intramolecular attack by a Cu-coordinated HO- species on the carbonyl group. Complex C In cephalosporins, coordination of the metal ion is by the carbonyl O-atom and the carboxylate group. Because the transition state is less stabilized than in A, the acceleration factor of metal ions for the hydrolysis of cephalosporins is lower than for penicillins. Complex D /3-Lactams with a basic side chain bind the metal ion to the carbonyl and the amino group in their side chain. This binding mode does not stabilize the tetrahedral transition complex and, therefore, does not affect the rate of... 

A number of antibiotics appear to require a transition metal ion as a cofactor. 

Antiarthritis drugs labelled gold compounds, 969 metal complexes, 758 Antibiotics ionophoric, 553 metal complexes selective binding, 552 transition metal ions, 728 Antibodies labelling... 

Bleomycin is a clinically useful family of glycopeptide antibiotic congeners with antitumoral activity. Cytotoxicity results from oxidative DNA damage. Bleomycin and transition metal ions form complexes that react with dioxygen and oxidize DNA. DNA damage is due to an activated form of iron bleomycin which forms from Fe -bleomycin in the presence of dioxygen and a source of electrons or from Fe -bleomycin in the presence of H2O2. 

Transition-metal ions cause an enormous increase in the rate of hydrolysis of penicillins and cephalosporins (Gensmantel et al., 1978, 1980 Cressman et al., 1969). For example, copper(ri) ions can enhance the rate of hydrolysis of benzylpenicillin 10 -fold, a change in the half-life from 11 weeks to 0.1 seconds at pH 7. In the presence of excess metal ions, the observed apparent first-order rate constants for the hydrolysis of the 3-lactam derivatives are first order in hydroxide ion but show a saturation phenomenon with respect to the concentration of metal ion which is indicative of the formation of an antibiotic/metal ion complex. A kinetic scheme is shown in (3), where M is... 

Kupka, T. 1997. P-Lactam antibiotics. Spectroscopy and molecular orbital (MO) calculations Part I IR studies of complexation in peniciUin-transition metal ion systems and semi-empirical PM3 calculations on simple model compounds. SpectrochirtL Acta. A 53 2649-2658. 

Despite these evident drawbacks, a broad variety of SOs have been used in CMPA-based enantiomer separations, including cyclodextrins, proteins, macro-cyclic antibiotics, chiral ion-pairing agents, amino acids in combination with transition metal salts, and crown ethers. Recent application for the separation of pharmaceutically relevant chiral compounds utilized P-cyclodextrins [46-48] charged cyclodextrins [49, 50], macrocyclic antibiotics [51, 52] and chiral ion-pairing agents [53, 54]. A more detailed discussion of CMPA-based enantiomer separation is beyond the scope of this chapter. The interested reader is referred to dedicated reviews [55, 56]. 

Truter, M. R. Structures of Organic Complexes with Alkali Metal Ions. Vol. 16, pp. 71-111. Umezawa, H., Takita, T The Bleomycins Antitumor Copper-Binding Antibiotics. Vol. 40, pp. 73-99. Vahrenkamp, H. Recent Results in the Chemistry of Transition Metal Ousters with Organic Ligands. Vol. 32, pp. 1-56. 

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