Antibiotics metal binding

There is concern over the toxicity of a nnmber of metals and metalloids, and their oxyanions. As for antibiotics, the genes for resistance are often plasmid-bome. There are several mechanisms that may operate—redaction, methylation, efflnx, and the synthesis of metal-binding metallothioneins. The following text illustrates aspects of these mechanisms. 

Xanthate-modified cellulose binds metal-TC tetracycline complexes and is evaluated to be an effective controlled release system for TCs complexes, owing to the metal-binding properties of these antibiotics. ... 

Related Compounds sumably some antibiotics are delicately balanced so as to be able to compete successfully with the metal-binding agents of the bacteria while not disturbing the metal processing by the host. There is evidence that at least some bacteria have developed resistance to antibiotics through the development of altered enzyme systems that can compete successfully with the antibiotic.133 The action of the antibiotic need not be a simple competitive one. The chelating properties of the antibiotic may be used in metal transport across membranes or to attach the antibiotic to a specific site from which it can interfere with the growth of bacteria. 

Cadmium(II) transport, over Hg(II) and Zn(II). 102-104 Carbon dioxide facilitated transport, 111 separated from nitrogen in ILMs, 146,150 Carbon monoxide facilitated transport, 112 reversible binding, 30-32 Carboxylate ionophore antibiotics, metal ion transport, 86 Carrier molecule effect on solute flux, 4 function in facilitated transport, 124 Carrier-facilitated transport—... 

A group of natural products, ionophores, which disrupt normal ion gradients, function as antibiotics by binding to metal ions and transporting them across cell membranes. One of... 

In a seminal paper appearing in 1969, Dietrich, Lehn, and Sauvage" described the first synthesis of a series of cryptands of the type 14. In part, it was the known alkali metal binding (and membrane transport behavior) of the natural antibiotic ionophores that provided the inspiration for the design of these then novel cage systems." ... 

The chemical production of hydroxyl radical, either by metal-mediated redox reactions or as a result of radiolysis products, can induce strand breaks in DNA. An example of a chemotherapeutic agent whose chemical production of activated oxygen is believed to be the critical step in its action is bleomycin, a naturally occurring antibiotic. The binding of metals to this and other antibiotics has been summarized in detail [1—3] and the material presented here is based on these reviews. 

Fig. 7.3. Structures of the metal binding antibiotics adriamycin (doxorubicin), R = CH3 (74), daunorubicin, R = H (74) and streptonigrin (75).

Anthraquinone, 1-hydroxy-calcium aluminum chelate compound, 1,2 metal complexes dyes, 6,86 Antiarthritis drugs labelled gold compounds, 6, 969 metal complexes, 6,758 Antibiotic M139163,2, 974 Antibiotics ionophoric, 6, 553 metal complexes selective binding, 6, 552... 

There are two general classes of naturally-occurring antibiotics which influence the transport of alkali metal cations through natural and artificial membranes. The first category contains neutral macrocyclic species which usually bind potassium selectively over sodium. The second (non-cyclic) group contains monobasic acid functions which help render the alkaline metal complexes insoluble in water but soluble in non-polar solvents (Lauger, 1972 Painter Pressman, 1982). The present discussion will be restricted to (cyclic) examples from the first class. 

The crowns as model carriers. Many studies involving crown ethers and related ligands have been performed which mimic the ion-transport behaviour of the natural antibiotic carriers (Lamb, Izatt Christensen, 1981). This is not surprising, since clearly the alkali metal chemistry of the cyclic antibiotic molecules parallels in many respects that of the crown ethers towards these metals. As discussed in Chapter 4, complexation of an ion such as sodium or potassium with a crown polyether results in an increase in its lipophilicity (and a concomitant increase in its solubility in non-polar organic solvents). However, even though a ring such as 18-crown-6 binds potassium selectively, this crown is expected to be a less effective ionophore for potassium than the natural systems since the two sides of the crown complex are not as well-protected from the hydro-phobic environment existing in the membrane. 

All of these methods fail to show the presence of the epimeric form of the tetracyclines and in most instances streaking of the spots is a problem. A basic improvement in the paper chromatography of these antibiotics was achieved by Selzer and Wright (47) and Kelly and Bryske (48) when they reported methods for the pretreatment of the paper with com-plexing agents to bind the metallic ions which may be present. 

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