Parallel Synthesis and Screening of Supramolecular Chemosensors that Achieve Fluorescent Turn-On Detection of Drugs in Saliva

Abstract

<div><div><div><p>We report here a parallel synthesis-driven approach to create a family of self-assembling dimeric sensors that we call DimerDyes, and its use for the rapid identification of salt-tolerant sensors for illicit drugs. We developed an efficient method that involves parallel synthesis and screening in crude form without the need to purify each potential sensor. Structurally diverse “hit” DimerDyes were re-synthesized, purified and were each shown to assemble into homodimers in water in the programmed way. DimerDyes provided a “turn-on” fluorescence detection of multiple illicit drugs at low micromolar concentrations in water and in saliva. The combination of multiple agents into a sensor array was successfully able to detect and discriminate between closely related drugs and metabolites in multiple important drug families. This report includes extensive NMR data on synthetic characterization, and on binding and assembly processes. It also includes UV-Vis and fluorescence spectroscopy data, and their use for quantitation and identification of drug-related analytes using multivariate statistical analysis. </p></div></div></div>

Mechanism of a Disassembly-Driven Sensing System Studied by Stopped-Flow Kinetics

“…The association and dissociation processes cannot be determined separately, and the fastest unimolecular reaction determines the time scale for the kinetic measurements. 36 The broadening observed in the 1 H NMR spectra for DimerDye− guest systems, 26,27 including the current system (Figure S3), suggests that the dynamics for these systems occur on the millisecond time-scale, making stopped-flow the suitable technique for real-time kinetic measurements. 36 The kinetics for DD1 2 disassembly upon dilution was measured by the appearance of fluorescence from monomeric DD1 (Figure 2b).…”

“…25 Analogues that include an integrated fluorescent component are called DimerDyes. 26,27 The selfassembly of DimerDyes stacks two dye copies in an antiparallel, quenching arrangement. The addition of a good guest out-competes homodimerization to form a host−guest complex, resulting in a turn-on fluorescence response (Scheme 1).…”

“…The current study focuses on the competing binding equilibria for the complexes of DimerDye1 (DD1) with the guest nicotine. Nicotine is a biologically relevant model analyte 27,29 that has multiple ionizable groups (pK a = 3.1 (pyridine) and 8.0 (pyrrolidine)), 30 allowing us to probe the effect of charge on multiple binding equilibria. We first characterize the general assembly and photophysical properties of the system using absorbance and steady-state fluorescence.…”

Synthesis of red fluorescent dye with acid gas sensitive optical properties and fabrication of a washable and wearable textile sensor

“…Such sensors will be referred to as chemosensors. [6][7][8][9][10] The most popular chemosensors can detect specific chemicals only in the liquid or solution phase, hence it will be useful for practical reasons to extend the application of chemosensors to the detection of the vapor phase of harmful or dangerous chemicals, such as volatile organic compounds or corrosive acids and bases. For example, it will be convenient and safe if workers can detect the gaseous phase of toxic chemicals and be alerted with only work clothes or technical textiles without electronic equipment.…”

Synthesis of novel coumarin-based acid vapochromic fluorescence dye showing change of both color and fluorescence emission spectrum for application to sensitive, reusable, and washable textile sensors

“…In particular, there are chemosensing dyes, which can detect specific dangerous or toxic chemical materials. [1][2][3][4][5][6][7] Most chemosensing dyes can sense the chemicals only in the solution phase. In the vapor phase, the sensing function would be very weak or even nonexistent.…”