Anthony W. Czarnik

Chemosensors of Ion and Molecule Recognition

Preface. Modification of Cyclodextrins to Control their Guest-Host Chemistry and Their Application as Chemosensors J.H.T. Luong. New Fluorescent Readouts for Protein Interactions, Gene Expression, and Membrane Potential R.Y. Tsien. Chemical Sensors Based on Field Effect Transistors Selective Recognition of Cations and Anions M.M.G. Antonisse, et al. Aqueous Sugar Sensing by Boronic-Acid-Based Artificial Receptors S. Shinkai. Solid State Supramolecular Optical Sensors O.S. Wolfbeis, et al. Fluorescent Chemosensors Which Take Profit from the Metal-Ligand Interaction L. Fabbrizzi, et al. Recognition, Transduction and Immobilisation: A Holistic Approach to Sensor Development D. Diamond, et al. Signal Transduction in Chemosensors of Modified Cyclodextrins A. Ueno, et al. Hydrogen Bonding Chemosensors for Metabolites and Nucleotides T.W. Bell, Z. Hou. New Approaches to Sensory Materials: Molecular Recognition in Conjugated Polymers. New Transduction Methodology T.M. Swager. Higher Generation Luminescent PET (Photoinduced Electron Transfer) Sensors A.P. De Silva, et al. Chemosensing of Monocyclic and Bicyclic Aromatic Hydrocarbons by Supramolecular Active Sites W.K. Hartmann, et al. Squaraine-Based Long Wavelength Fluorescent Chemosensors for Ions E.U. Akkaya. A Fluorescent Chemosensor with Selectivity for Hg(II). Chelatoselectivity Via Ligand Immobilization J. Yoon, et al. Cation-Responsive Fluorescent Sensors B. Valeur, et al. Fluorescent, Siderophore-Based Hydroxamate Chelators for the Detection of Transition-Metal Ions F. Fages. Author Index. Subject Index.

Desperately seeking sensors

The list of biologically active small molecules for which fluorescent sensors would be desirable is enormous. The list of sensors actually available is surprisingly small. The reason derives in part from a lack of communication between chemistry inventors and biology end-users. A new World Wide Web board has been created to address this need.

A FLUORESCENT CHEMOSENSOR SIGNALLING ONLY HG(II) AND CU(II) IN WATER

Geometric immobilization of polyamine ligands is expected to change their binding properties toward practical ion discrimination. Chemosensor 5 senses only two transition metal ions in water- Hg(II) (Kd≤1 μM) and Cu(II) (Kd 56 μM)- which can be compared with bindings of a non-immobilized reference compound (9-(trpnmethyl)-anthracene; 3) with Hg(II) (Kd 14 μM) and Cu(II) (Kd 39 μM). A related bridged cyclen derivative (7) showed no effect on fluorescence by any metal ion examined.

Inhibition of an HIV-1 Tat-derived peptide binding to TAR RNA by aminoglycoside antibiotics

Abstract Aminoglycoside antibiotics were found for the first time to inhibit an HIV-1 Tat-derived peptide binding to TAR RNA. The IC 50 values of neomycin, streptomycin, and gentamicin were determined as 0.92 μM, 9.5 μM, and 45 μM, respectively. In the absence of Tat peptide these antibiotics were found to cause mobility shifts of the TAR RNA on non-denaturing polyacrylamide gels. This is the first example, to our knowledge, of non-peptide or non-nucleotide like small molecules that bind to and induce a mobility shift of TAR RNA. It was further found that the antibiotics which demonstrate higher affinity for TAR are better inhibitors of the Tat/TAR interaction. Mutational and competition studies indicate that neomycin binds to the duplex domain of TAR RNA.

A sense for landmines

A heightened sense of smell, achieved by proxy through chemistry, offers solutions to problems where biologically based sensors are inappropriate. Detection of the TNT in landmines using fluorescent chemosensors is one example.

Discovery of selective, small-molecule inhibitors of RNA complexes—1. The tat protein/TAR RNA complexes required for HIV-1 transcription

We have developed a therapeutic program focusing on the inhibition of a human immunodeficiency virus-1 specific protein-RNA interaction. This program begins with a search for small organic molecules that would interfere with the binding of Tat protein to TAR RNA. The methodologies chosen to study the HIV-1 Tat-TAR interaction and inhibition include gel mobility shift assays, scintillation proximity assays, filtration assays, and mass spectrometry. These methods helped establish in vitro high-throughput screening assays which rapidly identified Tat-TAR inhibitors from our corporate compound library. Tat-activated reporter gene assays were then used to investigate the cellular activities of the Tat-TAR inhibitors. The cellular activity, selectivity, and toxicity data for select Tat-TAR inhibitors were determined. Evaluation of both the cellular data and the Tat-TAR inhibition results led to further testing in anti-HIV-1 infection assays.

Synthesis and characterization of a reactive binuclear co(III) complex. Cooperative promotion of phosphodiester hydrolysis

Abstract A binuclear Co(III) complex has been prepared that shows greater reactivity towards bis(p-nitrophenyl)phosphate than two equivalents of the parent mononuclear Co(III) complex.

Fluorescent chemosensing of catechol and catecholamines in water

It has been known for almost 35 years that catechol complexes reversibly to boronic acids. We observe that 2-anthrylboronic acid complexes catechol in water with Kd 330 microM and concomitant 20-fold reduction in fluorescence intensity. L-DOPA and dopamine behave similarly, suggesting a mechanism for the development of real-time sensing schemes.

Chelation‐enhanced fluorescence chemosensing of Pb(II), an inherently quenching metal ion

Pb(II) ion serves as a quencher of anthracene fluorescence both intermolecularly and in intracomplex systems reported to date. The advantages of intensimetric analyses showing increasing signal require the design of mechanistically novel fluorescent chemosensors capable of yielding enhanced fluorescence upon chelation of inherently quenching metals. We synthesized both 2‐ and 9‐derivatives of anthracene bearing the N‐methylthiohydroxamate ligand, which is capable of quenching fluorescence in the uncomplexed form and which shows some selectivity for Pb(II). Complexation of the 2‐derivative to Pb(II) results in rapid metal ion‐catalyzed hydrolysis, rendering this compound useless as a sensor with real‐time response. However, complexation of the 9‐derivative with Pb(II) results in a 13‐fold fluorescence increase, reversible upon dissociation of the metal ion. While blood lead analysis is a major potential application for fluorescent chemosensors, the present compound is insufficiently selective for this use.

Selective transport of ribonucleosides through a liquid membrane

Abstract Lipophilic salts of phenylboronic acid facilitate the transport of ribonucleosides across a ClCH 2 CH 2 Cl liquid membrane; deoxynucleosides, in general, are not transported in this system.