Compositions and systems are provided for the high efficiency quenching small water-soluble oligomers, or oligofluors, of from about 1-10 kd in size, where the oligofluors comprise multiple excimeric or exciplex forming fluorophores arranged on a scaffold, which are efficiently quenched by a quencher entity linked to the oligomer through a cleavable moiety. Fluorophores of interest include, without limitation, aromatic fluorophores such as pyrenes, e.g. benzopyrene, perylene, pyrene, etc. In some embodiments the oligofluor/quencher combination provides for a Stern-Vollmer constant (KSV) of greater than about 106 M−1, and may be greater than about 107 M−1, greater than about 108 M−1, or more. In some embodiments of the invention, the scaffold is a phosphodiester/glycoside backbone, e.g. an analog of a polynucleotide. The system of oligofluors and quenchers can be used in qualitative and quantitative screening and detection methods to detect any enzymatic, chemical or catalytic activity that can cleave the moiety between the quencher and scaffold.