Preparation of a conjugation-ready thiol responsive molecular switch

Abstract

In this work we synthesize molecular switches that are responsive to cysteine, homocysteine, and glutathione; three redox systems that make up the majority of the body’s antioxidant defenses. Synthesized spiropyran isomers with conjugation-ready linkages showed good selectivity of response to these major antioxidant thiols over nucleophilic amino acids; however the position of the linking group can affect selectivity and reversibility of the switching response. An isomer with selectivity for cysteine against GSH and Hcy was identified.

Negatively photochromic organic compounds: Exploring the dark side

“…The spiropyran 4 and the 4′-and 6′-hydroxymethyl analogues 23 and 24 have been used as sensors for thiol-containing amino acids 97,98 and the N-alkylthio derivative 25, when bound to a gold surface, has been employed as a reusable sensor for antibodies ( Figure 9). 99 In the presence of serum albumins the thermal ring opening of the 6,8-dinitrospirobenzopyran 4 to the zwitterion 5A was accelerated.…”

Redox Paradox: A Novel Approach to Therapeutics-Resistant Cancer

“…In contrast to the intracellular redox state, Cys/CySS is dominantly expressed in plasma. Blood and extracellular fluid possess major thiol-dependent redox nodes involving Cys and CySS, which have been associated with receptors and extracellular proteins, including matrix metalloproteinases (MMPs) (286,327). The Cys/CySS couple may function as an oxidant-reductant in redox switching, thus providing a means to oxidize-reduce proteins without the direct involvement of more potent oxidants-reductants.…”

Highly Sensitive and Selective Spiropyran-Based Sensor for Copper(II) Quantification

“…Given the aforementioned significance of copper in biological (aqueous) and industrial (organics) settings, there is keen interest in methods to measure the copper content. Current methods for copper quantification include inductively coupled plasma mass spectrometry (ICP-MS), 23 − 25 atomic absorption spectroscopy (AAS), 26 , 27 organic colorimetric sensors, 28 − 30 and fluorescent sensors. 31 , 32 Analytical methods such as ICP-MS and AAS offer parts per billion sensitivity, but these methods often require protracted sample extraction, preparation, and the use of sophisticated instruments, precluding use for rapid or in-the-field analysis.…”

“… 23 − 27 Fluorescent sensors can provide detection of copper ions without protracted sample preparations but still require advanced instrumentation to analyze the changes in fluorescence. 31 , 32 Optical, colorimetric sensors for copper offer the potential for naked-eye detection of copper ions without extensive sample manipulation or the use of large instrumentation 28 − 30 and represent a low-cost, rapid alternative to laboratory testing methods. Furthermore, the development of inexpensive portable UV–vis spectrometry instruments means that highly quantitative sub-micromolar readings could one day be taken directly in the field.…”