Synthesis of 1,8-naphthalimide-based probes with fluorescent switch triggered by flufenamic acid

Abstract

In this work, we report the synthesis of novel fluorescent molecules, based on 1,8-naphthalimide thio- and amino-derivatives, designed to display an OFF-ON and ON-OFF photoelectron transfer fluorescence switch upon interaction with a proton-donor drug. We have functionalized the new probes to allow easy formation of a covalent link to polymer matrices, for future applications as drug delivery sensors. We have investigated the fluorescent switch of the new probes using flufenamic acid (FA, pKa 3.65), a water insoluble, non-steroidal anti-inflammatory drug, as a model drug and proton source. The rapid interaction of the new probes with FA resulted in fluorescence enhancement or decrease and a large Stokes shift, all of which allowed the detection of the drug in the nanomolar range. The new 1,8-naphthalimide fluorescent dyes reported in this work are interesting tools for the detection and quantification of acidic drugs and biomolecules.

Naphthalimide-based optical turn-on sensor for monosaccharide recognition using boronic acid receptor

“…4 Over the past few decades, uorescence organic molecules have been used for selective recognition of a wide range of analytes. [5][6][7] Development of small molecules which are able to interact with carbohydrates requires special recognition moieties capable of strong binding under physiological conditions. Among various materials for saccharide detection, use of boronic acid and its derivatives has attracted a great deal of attention because of their strong interactions with sugars.…”

Fluorescent Imprinted Nanoparticles for the Effective Monitoring of Irinotecan in Human Plasma

“…Such derivatives have been already employed as fluorescent MIP monomers [ 26 , 27 , 28 ]; for example, monomer 5 was employed by Rouhani et al to develop a MIP sensor for caffeine, which showed a quenching of its fluorescence upon binding to the template with a limit of detection of 6.3 μM [ 29 ]. These very fluorescent molecules have been also used as probes for the detection of acidic drugs, biomolecules [ 30 ], and anions [ 31 ]. We have identified a small set of naphtalimide monomers ( 2 – 6 ) and synthesised them by literature methods [ 32 , 33 , 34 , 35 ].…”

Induction of Mycobacterium Tuberculosis Lipid-Specific T Cell Responses by Pulmonary Delivery of Mycolic Acid-Loaded Polymeric Micellar Nanocarriers

“…To overcome this challenge and increase the effective dose of MA, we encapsulated MA into a micellar nanocarrier (MA-Mc) using the controlled self-assembly of PEG-PPS, which can form diverse nanocarrier morphologies to efficiently deliver hydrophobic and hydrophilic moieties to APCs ( 21 ). To track the intracellular release of MA from micelles following uptake by cells, we modified the PEG-PPS copolymer by attaching an acid sensitive fluorophore (ASF, λ ex = 395 nm, λ em = 505 nm) ( 29 ) to the terminal end of the PPS block (PEG-PPS-ASF; Figures S1 , S2A ). The ASF contains an aminoquinoline ring, and the protonation of the tertiary amine within the ring leads to 98% quenching of fluorescence (Figure S1 ) ( 30 ).…”

“…An acid-sensitive fluorophore (ASF, λ ex = 395 nm, λ em = 505 nm) derived from a 1,8-naphthalamide was synthesized as previously described ( 29 , 30 ). The fluorophore was then modified to introduce a -SH containing linker on the naphthalimide ring for conjugation to PEG-PPS ( 31 ) (Figure S1 ).…”

“…We synthesized two separate PEG-PPS fluorescent conjugates, each possessing the same copolymer but with distinct fluorophores to characterize MA delivery to and presentation by DCs both in vitro and in vivo . MA-loaded acid-sensitive fluorophore-conjugated micelles (MA-ASMc) ( 29 ) were employed to verify lysosomal delivery within bone marrow derived DCs (BMDCs) in vitro by confocal microscopy. Following intranasal administration, MA-ASMc additionally supported flow cytometric analysis of cellular biodistributions while MA-loaded micelles conjugated to a near-infrared fluorescence (NIRF) sensitive fluorophore (MA-NIMc) allowed assessment of the organ level biodistributions.…”