Synthesis and Self‐Assembly of Bay‐Substituted Perylene Diimide Gemini‐Type Surfactants as Off‐On Fluorescent Probes for Lipid Bilayers

Abstract

Interest in bay‐substituted perylene‐3,4:9,10‐tetracarboxylic diimides (PDIs) for solution‐based applications is growing due to their improved solubility and altered optical and electronic properties compared to unsubstituted PDIs. Synthetic routes to 1,12‐bay‐substituted PDIs have been very demanding due to issues with steric hindrance and poor regioselectivity. Here we report a simple one‐step regioselective and high yielding synthesis of a 1,12‐dihydroxylated PDI derivative that can subsequently be alkylated in a straightforward fashion to produce nonplanar 1,12‐dialkoxy PDIs. These PDIs show a large Stokes shift, which is specifically useful for bioimaging applications. A particular cationic PDI gemini‐type surfactant has been developed that forms nonfluorescent self‐assembled particles in water (“off state”), which exerts a high fluorescence upon incorporation into lipophilic bilayers (“on state”). Therefore, this probe is appealing as a highly sensitive fluorescent labelling marker with a low background signal for imaging artificial and cellular membranes.

Mutually Exclusive Cellular Uptake of Combinatorial Supramolecular Copolymers

“…Therefore, both the amine‐ and the guanidine‐functionalized discs require a charge density of only three cationic groups per monomer for uptake of their corresponding supramolecular polymers. The high density of positive charges present in the supramolecular polymers evidently favors cellular uptake but conveniently avoids the need for seven to eight positive charges, typical in covalent systems, and is in line with observations on self‐assembling vesicles . The uptake of both these supramolecular polymers was shown to be rather fast as both cationic discs co‐localized with the cellular membrane within minutes and internalized after 30 minutes (Figure S7, S8).…”

“…uptake but conveniently avoids the need for seven to eight positive charges, typical in covalent systems, and is in line with observations on self-assembling vesicles. [32,33] The uptake of both these supramolecular polymers was shown to be rather fast as both cationic discs co-localized with the cellular membrane within minutes and internalized after 30 minutes (Figure S7, S8). Incubation of al arge cohort of Hela cells for 16 h, resultedi namore efficient uptake for the 3G-disc compared to 3NH2-disc ( Figure S9).…”

Progress in the synthesis of perylene bisimide dyes

“…It is only recently that Schenning and Brunsveld published a one-pot high-yielding procedure for the preparation of a monobay dihydroxylated PBI directly from a core-unsubstituted precursor (see the section "Direct hydroxylation reactions", Scheme 56). 118 Matile applied another approach to bayhydroxylated PBIs. Initially, 1,7-dibromo PBI 4a was reacted with allyl alcohol in the presence of NaH to give 89 in 55% yield.…”

“…The reaction of 1,7-4d with n-octylbromide in the presence of K 2 CO 3 in DMF furnished 93 in only 28% yield (Scheme 24). 118 Fernández-Lázaro and co-workers proposed another way to access alkoxylated PBIs. 120 The method based on the fluorideassisted reaction of halogenated PBIs with S or O reagents was an extension of their studies of fluoride-mediated functionalization of core-unsusbtituted PBIs (vide infra).…”

“…178a-c, in low to moderate yields (Scheme 56). 118 The literature survey may create some confusion, as it was reported that similar conditions led to 1,7-dihydroxy-PBI. 52 However, in the latter case the assignment was based exclusively on the 1 H NMR spectrum.…”