Summary of recent advances Fluorescent dyes based on small organic molecules that function in the near infra red (NIR) region are of great current interest in chemical biology. They allow for imaging with minimal autofluorescence from biological samples, reduced light scattering and high tissue penetration. Herein, examples of ongoing NIR fluorophore design strategies as well as their properties and anticipated applications relevant to the bioimaging are presented.

At elevated levels, homocysteine (Hcy, 1) is a risk factor for cardiovascular diseases, Alzheimer's disease, neural tube defects, and osteoporosis. Both 1 and cysteine (Cys, 3) are linked to neurotoxicity. The biochemical mechanisms by which 1 and 3 are involved in disease states are relatively unclear. Herein, we describe simple methods for detecting either Hcy or Cys in the visible spectral region with the highest selectivity reported to date without using biochemical techniques or preparative separations. Simple methods and readily available reagents allow for the detection of Cys and Hcy in the range of their physiologically relevant levels. New HPLC postcolumn detection methods for biological thiols are reported. The potential biomedical relevance of the chemical mechanisms involved in the detection of 1 is described.

The determination of cysteine and homocysteine levels is of great current interest for the monitoring of desease states. A new colorimetric method for the simultaneous detection of l-cysteine and l-homocysteine has been developed. A fluorescein derivative reacts with the above amino acids, producing their respective thiazolidines resulting in color changes. Interference from other amino acids and proteins is minimal.

Simple water-soluble lanthanum and europium complexes are effective at detecting neutral sugars as well as glycolipids and phospholipids. In solutions at physiologically relevant pH the fluorescent lanthanum complex binds neutral sugars with apparent binding constants comparable to those of arylboronic acids. Interference from commonly occurring anions is minimal. The europium complex detects sialic acid-containing gangliosides at pH 7.0 over an asialoganglioside. This selectivity is attributed, in large part, to the cooperative complexation of the oligosaccharide and sialic acid residues to the metal center, based on analogous prior studies. In MeOH, lysophosphatidic acid (LPA), a biomarker for several pathological conditions including ovarian cancer, is selectively detected by the europium complex. LPA is also detected via a fluorescence increase in human plasma samples. The 2-sn-OH moiety of LPA plays a key role in promoting binding to the metal center. Other molecules found in common brain ganglioside and phospholipid extracts do not interfere in the ganglioside or LPA fluorescence assays.gangliosides ͉ lysophosphatidic acid ͉ salophenes ͉ saccharides N ature uses tools such as lectins for the molecular recognition of saccharides. An important mode of lectin binding involves the coordination of a carbohydrate ligand to a metal center. C-type lectins recognize saccharides in a calciumdependent manner (1). The similar properties of lanthanides and calcium render trivalent lanthanide ions useful substitutes for Ca 2ϩ in studying proteins (2). Herein we describe the utility of water-soluble salophene (3)-lanthanide complexes toward addressing three current challenges: (i) the detection of neutral carbohydrates at physiologically relevant pH, (ii) the selective detection of gangliosides, and (iii) the selective detection of lysophosphatidic acid (LPA). Results and DiscussionDetection of Neutral Sugars at Physiological pH. A main problem in the detection of neutral sugars with artificial receptors is competitive binding by bulk water. Elevated solution pH is therefore typically required to attain a useful degree of coordination and signal transduction in the most innovative new metal-based detection methods (4, 5). There is an unmet demand for biomimetic sugar-sensing agents that function in neutral buffer solution (4, 5). Because La 3ϩ and Ca 2ϩ exhibit relatively strong affinity for saccharides as compared with most other metal ions (6, 7), we hypothesize that 1 (Fig. 1) may be useful for detecting sugars in neutral aqueous media. Interestingly, lanthanides can extend their ligand coordination number by the addition of either neutral or charged ligands through ligand-sphere extension, leading to highly coordinated complexes (8).Addition of saccharides (1.1 ϫ 10 Ϫ3 M) to a solution of 1 (5.53 ϫ 10 Ϫ6 M, 0.1 M Hepes buffer, pH 7.0) promotes readily monitored increases in emission (Figs. 1 and 2) (ref. 9 and references therein). Lanthanide coordination to salens whereby the ligand conformation is brought into a mor...

Several discreet sugar-boronate complexes exist in solution. This is due to the complex equilibria between isomeric species of even the simplest monosaccharides. In the current investigation, we determine the regio- and stereochemical features of the various equilibrating sugar isomers that induce signal transduction in boronic acid chemosensors such as 1 as well as 2 and 3. We present a unique example of a chemosensor (1) that is selective for ribose, adenosine, nucleotides, nucleosides, and congeners. As a result of this study, we are able to predict and achieve selective fluorescence and colorimetric responses to specific disaccharides as a consequence of their terminal sugar residue linkage patterns and configurations. We also find that the combined use of chemosensors exhibiting complementary reactivities may be used cooperatively to obtain enhanced selectivity for ribose and rare saccharides.

This review covers the approximately two-year period since our last review (A1), roughly from January 2004 through December 2005. A computer search of Chemical Abstracts provided most of the references for this review. Other citations were found through individual searches by the various authors who wrote a particular section of this review. In an effort to more effectively accomplish this goal, we have included authors who are experts in the various subtopics of this review. Coverage is limited to articles that describe new developments in the theory and practice of molecular luminescence for chemical analysis in the ultraviolet, visible, and near-infrared region.Citations may be duplicated between sections due to articles with contents that span several topics. However, in an effort to reduce the length of this review, we have attempted to limit this kind of duplication. In general, citations are limited to journal articles and usually do not include patents, proceedings, reports, and dissertations.We have tried to focus on important advances of general interest and relevance to the field of analytical chemistry, rather than extensions of previous advances. This was done in an effort to continue our recent attempts to significantly reduce the length of this biennial review. In addition, we have also expanded our description of individual citations for better clarification of content where necessary.Although we are not able to provide extensive coverage of developments of relevance to broad areas such as chromatography and biological sciences, we have tried to include major review articles and chapters relevant to these topics. If you feel that we omitted an important article published during the above referenced time period, please forward the reference to one of us and we will be certain to consider it for the next review.

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