Farhangi, ShivaDuhamel, Jean2017-09-252017-09-252016-09-13http://dx.doi.org/10.1021/acs.macromol.6b01295http://hdl.handle.net/10012/12444This document is the Accepted Manuscript version of a Published Work that appeared in final form in Macromolecules, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.macromol.6b01295Over the years, fluorescence quenching experiments have provided a robust analytical means to retrieve information about the internal dynamics of macromolecules in general and the long range polymer chain dynamics (LRPCD) of linear chains in particular. This report reviews the results obtained to. date with the two main fluorescence experiments based on collisional quenching that have been used over the years to describe LRPCD. These experiments involve the labeling of a chain with dyes and quenchers either at the ends of a monodisperse chain for fluorescence quenching end-to-end cyclization (fqEEC) experiments or randomly along a polydisperse chain for fluorescence decay analysis with the fluorescence blob model (FBM). The advantages and disadvantages of these two types Of experiments are discussed as well as their range of applications and applicability to the field of protein folding. In particular, this Perspective illustrates how fqEEc experiments are being applied to probe loop formation in polypeptides and how FBM analysis of randomly labeled polypeptides could help determine the size of foldons which are expected to solve Levinthal's long-standing paradox.enEnd-To-EndUnfolded Polypeptide-ChainsIntramolecular Contact FormationSingle-Molecule FretIntrinsically Disordered ProteinsPyrene Excimer FluorescenceTriplet Energy-TransferCyclization DynamicsSpectroscopic RulerBlob ModelArticle