We are developing novel chemosensors based on the principles of hydrogen bonding, host preorganization and host-guest complementarity. Our artificial receptors generally consist of heterocyclic and carbocyclic rings fused together to form a molecular cleft lined with hydrogen-bonding sites. A guest analyte binds to this cleft by means of complementary hydrogen-bond donor and acceptor groups. The binding event is signaled by a chromophore or fluorophore that is intrinsic to the receptor structure. We have used this approach to make artificial receptors for creatinine, urea, amino acids, and bicarbonate. For example, a hexagonal lattice receptor was reported previously to bind urea with a modest bathochromic shift of the longest wavelength absorption band. Urea binding, either in homogeneous solution or by extraction from water into an organic solvent, produces 50-96% quenching of the fluorescence emission at 414 nm. Quenching effects for urea binding by some newer, structurally related receptors are also reported. A novel approach to fluorescence detection of nerve toxins by means of fused-ring heterocycles is also presented. In this case, the heterocyclic fluorophore does not recognize the analyte by reversible complexation via hydrogen bonds. Instead, the heterocycle is designed to take advantage of the reactivity of halogenated organophosphates or phosphonates, forming a fluorescent adduct. Design of several substituted isoquinolines and their optical response to nerve toxin surrogates are described.