Designing reactivity-based responsive lanthanide probes for multicolor detection in biological systems

•Survey of luminescent lanthanide probes operating via a reactivity-based analyte sensing mechanism is presented.•Synthetic approaches to prepare cyclen derivatives to complex lanthanides are described with emphasis on substitution patterns especially useful for probe design.•Red-absorbing near infrared-emitting lanthanide complexes incorporating hydroporphyrin antennae are described. Synthetic approaches to hydroporphyrins are surveyed.•Tactics for the late-stage diversification of advanced lanthanide complexes are reviewed with an emphasis on Cu-catalyzed azide-alkyne cycloadditions. Strategies for the design and synthesis of responsive luminescent probes based on lanthanide complexes are surveyed. The sensitive detection of analytes ranging from ions to small molecules to large biomolecules such as enzymes in complex biological milieu drives the quest for even more selective probes with improved photophysical properties and broad availability for non-specialists. Here, reactivity-based probes, i.e. those in which the sensing event is accompanied by the breaking of a covalent bond are reviewed, with an emphasis on the strategies that could be generalized to the detection of additional analytes. Syntheses providing advanced cyclen-based ligands with minimum effort, as well as those that enable post-complexation modification of lanthanide-bound structures are presented.