Ion-Selective Electrodes With Ionophore-Doped Sensing Membranes

2560 Supramolecular devices
H 3 C
C 7 H 15
N
O
O
H 3 C
N
C 7 H 15
O
O
O
O
H 3 C
N
C 7 H 15
O
O
H 3 C
O
O
O
O
C 12 H 25
O
O
O
O
O
O
Na + -I
Na + -II
O
O
CH 2 CH 2
O OC 2 H 5
O OC 2 H 5
O O
CH 2
CH 2
O
O
O
Na + -III
Na + -IV
antibiotics were soon followed by more selective synthetic
ionophores binding Na + with multiple carbonyl groups. A
particular successful ionophore of that generation is Na + -I
(10 2.3 -fold selectivity over K + ), which has been used
successfully for intracellular measurements despite the high
K + concentrations in this environment. 31 Many ionophores
introduced subsequently were macrocyclic crown ethers
with oxygens as the recognition sites, as in the case of
the K + ionophores too. With its smaller size, Na + fits well
into 15-crown-5. Not surprisingly, the most successful biscrown
ether ionophores have two 12-crown-4 macrocyclic
rings, between which the Na + is bound with eight ion–ether
interactions (e.g., the commercially successful Na + -II with
a10 2.1 -fold selectivity over K + ). 95 As in the case of K +
selective bis-crown ethers too, the conformational freedom
of the bis-12-crown-4 ethers is large, which limits the
achievable selectivity, and as in the case of K + ISEs
too, extremely successful bridged calix[4]arenes have been
proposed. Na + -III with a 10 5.3 -fold selectivity over K + is
an outstanding example. 96 An alternative approach relying
largely on steric repulsion to exclude larger ions and prevent
the formation of complexes between one ion and two
ionophores is exemplified by Na + -IV (10 3.0 -fold selectivity
over K + ). 97
Interest in the analysis of Li + , the smallest alkali metal
ion, using ISEs stems predominantly from its use as a
mood-stabilizing drug. 4, 98 The most important interferent
in clinical measurements is Na + , which occurs in blood in
a concentration of approximately 140 mM. Early work with
diamide ionophores 4 such as Li + -I, which forms 1 : 2 complexes
with Li + , found selectivities (10 2.3 -fold selectivity
over Na + ) barely permitting the first successful measurements
in blood. 99, 100 In 1987, the first commercial clinical
analyzer measuring Li + with ISEs became available. 101
While various approaches were taken to improve the selectivity
over Na + , the most successful one is arguably the
one in which 1,4,8,11-tetraoxacycolotetradecane was decorated
with bulky substituents hindering the formation
N
N
O
O
O
O
O
O
O
CH 2 CH(CH 3 ) 2
N CH2 CH(CH 3 ) 2
O
CH 2 CH(CH 3 ) 2
N
CH 2 CH(CH 3 ) 2
O
O
O
O
Li + -I
Li + -II
Li + -III