Chemistry Reference
In-Depth Information
and at the opposite surface, the process is reversed to leave the metal cation
and the anionic ionophore on the other side of the membrane. The ionophore
must bind another cation (usually a proton) to return to its original starting
point.
The anionic ionophores are highly selective for particular metal cations, and
both kinetic and thermodynamic terms determine which cation is selected. Note
that the thermodynamic stability of the metal-ionophore complex does not
always determine the transport rate. For example, nigericin forms a much more
stable complex with potassium but transports sodium much more quickly. In
the presence of both sodium and potassium, however, the extra stability of the
nigericin-potassium complex results in the preferential transport of potassium
over sodium (4).
Selectivities of ionophores are shown in Table 8.1 (5, 6). The carboxyl group
may (e.g., nigericin) or may not (e.g., monensin
2
) be involved in cation liganding
via an ionic bond. Monensin has six liganding oxygen atoms but none for ionic
bonds, and it is a weaker complexing agent than is nigericin. Lasalocid
4
can
form a singly charged complex with doubly charged cations such as Ca
2
+
.The
broad specificity of lasalocid results from the metals sitting on top rather than
within the oxygen system of the ionophore. For nonactin
5
, the ester carbonyl
oxygen atoms and the ether oxygen atoms are all liganding and form the apices
of a cube. Nonactin adopts a conformation resembling the seam of a tennis
ball (5).
Commercial interest in the polyketide polyethers stems from their antibiotic
activity. Many polyethers of the class are potent coccidiostats and can control
coccidial infections in poultry when added at approximately 100 ppm to the feed
(7). Cocciodosis is caused from an infection in the digestive tract by parasitic
protozoa, most commonly in poultry from the genus
Eimeria
. Monensin was
the first polyether antibiotic to be patented and was released onto the market
in 1971. It is still widely used today and is marketed under the tradename of
Coban
®
(Elanco, Toronto, Ontario, Canada). After monensin treatment, coccidia
have been observed to literally explode at one stage in their lifecycle because
of the increase in osmotic pressure generated from the exchange of sodium out-
side the organism for protons inside (4). Lasalocid was launched in 1976 under
the tradename Avatec
®
(Alpharma, Inc., Bridgewater, NJ) (7), and unlike mon-
ensin, it cannot be used for laying hens and must be withheld from poultry for
TABLE 8.1
Ionophore selectivities (5, 6)
Ionophore
MW
Selectivity sequence
Nigericin (
1
)
724
K
>
Rb
>
Na
>
Cs
>>
Li
Na
K
>
Rb
>
Li
>
Cs
Monensin A (
2
)
670
Cs
>
Rb
≈
K
>
Na
>
Li; Ba
>
Sr
>
Ca
>
Mg
Lasalocid (
4
)
590
Nonactin (
5
)
736
NH
4
>
K
≈
Rb
>
Cs
>
Na
Tetronasin (
10
)
602
Ca
>
Mg
>
Na
