the resulting ternary complex. The stronger interaction between
analyte and receptor improves the limit of detection (LOD) of the
analyte and permits use of the sensor over a much wider pH and
concentration range, making the detection technique more sensi-
tive and robust.
In terms of pH, an example of enhancement due to helper ligands
can be seen in our initial work on detection of catecholamines (CAs).
These“fight-or-flight”hormones, which are part of the sympathetic
nervous system, are released by the adrenal glands in response to
stress( 111 ). CAs produced from the amino acids phenylalanine
andtyrosinecontainthe1,2-dihydroxybenzene(catechol,Cat)group
and either a primary or secondary amine group. CAs are water
soluble and circulate in the bloodstream with a half-life of approxi-
mately 3 min ( 112 ). Overstimulation and/or damage of brainstem
nuclei can lead to CA toxicity. CA toxicity can also be caused by
pheochromocytoma,neuroendocrinetumorsintheadrenalmedulla,
and carcinoid syndrome (carcinoid tumors in the gastrointestinal
tract and/or lungs), as well as by a deficiency in monoamine oxidase
A, which is normally responsible for the degradation of CAs. High
levels of CAs have been associated with various functional
and degenerative cardiovascular disorders, such as angina pectoris,
arterial hypertension, and atherogenesis ( 113 ). Decreased dopa-
mine (DA) levels have been linked to Parkinson's disease and atten-
tiondeficithyperactivitydisorder(ADHD),whileelevatedlevelscan
cause mood swings, psychosis, and other neurotic disorders
( 114 – 116 ). Increased levels of epinephrine (Epi) (when properly
administered) can help the body reduce negative allergenic
responses and regenerate lost liver cell functions (117,118). For all
these reasons, rapid detection of CAs in blood and urine can provide
vital information that might aid in more efficient diagnosis as well
as more effective treatment of various disease states.
Current methods of detection for CAs in biological fluids
(urine, plasma, and serum) involve chromatographic separation
coupled to either electrochemical(119,120) or optical ( 121 ) tec-
hniques. However, most optical methods rely purely on the native
fluorescence of CAs (lex280 nm,lem310 nm) ( 122 ), which have
small Stokes shifts and suffer from signal losses due to reabsorp-
tion; others involve pre- or postcolumn derivatization with various
fluorophores, such as naphthalene-2,3-dicarboxaldehyde ( 123 ),
1,2-diphenylethylenediamine (124,125), or fluorescamine ( 126 ).
These methods all require significant time for separation using
expensive instrumentation and thus are not feasible for rapid
CA detection.
We have investigated the potential of lanthanide complexes for
the detection of CAs, specifically DA, Epi, and norepinephrine
22 MORGAN L. CABLEet al.