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Pilani Campus

CHEM F343: Inorganic Chemistry III

Lecture-3
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Inorganic Elements in Biological
Systems: revision

• 30 essential elements
• 6 bulk or structural elements
• 5 macromineral elements
• 19 trace elements.
J. Chem. Edu., 1985, 62, 917-923
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Inorganic elements in biological
system: revision
• The elements are essential for life but excess results in toxic side effects
• Large concentration of any metal ions may compete for other
coordination sites that normally bind a different metal ion and activity of
that site may get lost.
• Hence, balance distribution of elements is required for the health of
living cells.

Effect

Conc
Lack of element Deficiency Optimal supply Excess Toxic dose
(Death) (Disease) (Disease) (Death)

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Metal ion uptake
Metal Ion Uptake : Transmembrane Ion Transport
(three species in the membrane)

Three types of molecular species present in the

membrane to effect ion transport

1. Low/high MW carrier ligands (ionophores) that ferry the ion

across the membrane
2. Membrane-spanning peptides or proteins that define a
hydrophilic channel so that the ion can flow
3. Membrane-bound enzymes that use the energy derived
from ATP hydrolysis to pump ions across the membrane

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Transport molecules
• Cells have evolved the means to transport molecules,
macromolecules and even larger particles across their plasma
membrane.
• It is now known that specific transporting membrane proteins
called transport molecules.
• Transmembrane proteins are either one protein molecule or a
part of the larger protein structures that run across the bilayer

Different modes of action of transport molecules

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Transport molecules: another way

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Transport molecules: another way

Schematic diagram of transport molecules functioning as uniport, symport and

antiport systems. Symport and antiport systems are called co-transport systems.
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Transport molecules: another way

• Carrier transport protein which

undergoes conformational changes
while transporting a solute across the
membrane.
• The solute binds at the active site of
the carrier protein and is transported
by facilitated diffusion along the
concentration gradient.
• After the molecule is transported the
carrier protein resumes its original
shape.
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Transport molecules: another way

Lipid
bilayer

When an anion binds at the outer face, the conformation of the protein changes and
the channel opens for the anion to move across and anion binding site (1-3).
This causes another anion to bind on this site leading to the formation of original
conformation which is the passage of second anion in the opposite direction.
It recreates the binding site on the outer surface (4-6).
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Ionophores: idea

✓ Ionophores are non protein carrier ligands that

possess polar functional groups to lend H2O
solubility to the metal-free complex
✓ After binding a Mn+, these functional groups fold
inward, leaving a hydrophobic surface: solubility in
the lipid membrane
✓ Ionophores bind cations and even anions (currently
known) with a high degree of selectivity.
✓ Many are macrocycles that contain oxygen ligands
in the form of C=O and/or ether functionality

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Ionophores: structure

(A) Macrocyclic ethers, (B) Peptides, and (C) Carboxylate ionophores

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Ionophores: specificity vs.
selectivity
• Ionophores tend not to show specificity (the ability to
bind one particular metal ion) but do possess a high
degree of selectivity (although they can bind to several
metal ions, such ligands exhibit a strong preference for
one particular ion)
• Ionophores bind metals predominantly through oxygen
ligands, and so selectivity is based primarily on
considerations of ion charge and size
• The “best-fit” criterion becomes important as the
ligands bind metal ions optimally when the ionic radii
best match the hole size in the macrocycle.

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Ionophores: specificity vs.
selectivity (Valinomycin)
• The antibiotic valinomycin shows high selectivity for K+
transport.
• However, this selectivity is not entirely based on “best-
fit” criteria, since K+ and Na+ can both be accommodated
in the central core
• Valinomycin also distinguishes these ions on the basis of
hydration energies
• The (q2/r) ratio is higher in Na+. So the difference in
solvation energy strongly favors the binding of K+
• The energetics of solvent removal is an important aspect
of ion-selectivity.
• The ligand atoms must be able to coordinate to the metal
center to make up for the loss of hydration energy, and
so there is a trade-off between solvent loss and ligand
binding
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Ionophores
• Ionophore don’t have metal ion specificity but posses high
degree of selectivity.
• Binds with O atom, so selectivity depends on ionic charge
and size
• Example:
Valinomycin

H3C CH3
CH O O O CH3 O
H H
N CH C O C C N C C O CH C

H CH H CH
H3C CH3 H3C CH3 3
L-valine D-hydroxy- D-valine L-lactic
isovaleric acid acid

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Valinomycin-potassium complex

H D-Val
• Selective for K+
L-Val
L
• Selectivity criteria is not only
O best fit but also hydration
L
O
O
L-Val
energy
K+
O • Ehyd of Na+ = -71.9 kCalmol-1
H

• Ehyd of K+ = -55 kCalmol-1

D-Val O
O

D-Val
H
L-Val L

• Energetics of solvent removal is an important aspect of

ion selective uptake.
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Ionophores
• Ionophores typically bind alkali and alkaline earth metal
ions
• The intracellular and extracellular concentration of these
ions are very different, and the maintenance of
transmembrane concentration gradients by active
transport processes is vital to normal cell metabolism.
• Ionophores relax the concentration gradient and hence
acts as active antibiotics.

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Ionophores: metal selectivity

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Ionophores: metal selectivity

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Siderophores

Low/high MW Fe(III) Chelators, produced under low Fe

conditions

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Siderophores:

• Functions of Siderophores: must solubilize the iron

(solubility product of Fe(OH)3 is 10-39).
• must assist the transport of highly charged ions
across a hydrophobic membrane
• To effect the solubilization
• Siderophore binds iron tightly
• Binding constant ~1030 for tris-hydroxamate type
• Binding constant ~1045-52 for catechol type

• Large value of latter might be attributed to increase in –ve

charge
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Siderophores

• Release of iron from Siderophores

• Old thoughts: Esterase hydrolyses the Siderophore
backbone, destructing it and releasing iron
• But structure analogue lacking these ester bonds are
reported for iron uptake
• Current evidence: Release mechanism follows the reduction
of iron to Fe(II), which binds weakly K ~ 108 M-1 and
displaced from siderophores by protonation
• Iron bearing siderophore complexes exhibits higher
hydrophilic character then ionophores and hence requires
the assistance of membrane protein for translocation.

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