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Bifunctional linker-scaffolds (compounds 1-3) were designed to meet several criteria for solid-phase syntheses of bivalent ligands. They have two amine-functionalized arms that can be differentially protected. Elaboration of these arms could give ligand-pharmacophore dimers wherein the two active components are held reasonably rigidly at around 10 A separation. Their bifunctional design also enables reactions of libraries with libraries to amplify diversity in a truly combinatorial fashion. Molecules 1-3 are also designed so that cleavage of the linker liberates the scaffold entity into solution under conditions that create only byproducts that should not interfere with biological assays. Thus they contain 2-nitrobenzene sulfonamide components that cleave in the presence of good nucleophiles. In the event, the linker-scaffolds 1-3 were prepared (Schemes 1 and 2). The N-benzyl system 2 was shown to have good stability to the types of conditions that might be used to functionalize the scaffold arms and to be sufficiently labile to the cleavage nucleophile (vide infra). The nucleophiles generally used to cleave nitrobenzene sulfonamides either generate undesirable byproducts (thiophenol or alkane thiols) or proved to be insufficiently reactive for the required solid-phase transformations (n-propylamine). However, sodium sulfide was investigated as a new alternative and shown to be a highly reactive cleavage agent that gives only volatile byproducts and sodium hydroxide. It is suggested that sodium sulfide is a highly desirable nucleophile for cleavage of 2-nitrobenzene sulfonamides, in general. The linker-scaffolds 1-3 were used to prepare a small library of bivalent ligands targeted to a protein receptor having charged cavities separated by approximately 10 A. These systems were made from guanidine, pyridinium, carboxylic acid, and sulfonic acid constituents (Tables 1 and 2).