Differential Tuning of the Electron Transfer Parameters in 1,3,5-Triarylpyrazolines: A Rational Design Approach for Optimizing the Contrast Ratio of Fluorescent Probes

Abstract

A large class of cation-responsive fluorescent sensors utilizes a donor-spacer-acceptor (D-A) molecular framework that can modulate the fluorescence emission intensity through a fast photoinduced intramolecular electron transfer (PET) process. The emission enhancement upon binding of the analyte defines the contrast ratio of the probe, a key property that is particularly relevant in fluorescence microscopy imaging applications. Due to their unusual electronic structure, 1,3,5-triaryl-pyrazoline fluorophores allow for the differential tuning of the excited state energy ΔE00 and the fluorophore acceptor potential E(A/A−), both of which are critical parameters that define the ET thermodynamics and thus the contrast ratio. By systematically varying the number and attachment positions of fluoro-substituents on the fluorophore π-system, ΔE00 can be adjusted over a broad range (0.4 eV) without significantly altering the acceptor potential E(A/A−). Experimentally measured D-A coupling and reorganization energies were used to draw a potential map for identifying the optimal ET driving force that is expected to give a maximum fluorescence enhancement for a given change in donor potential upon binding of the analyte. The rational design strategy was tested by optimizing the fluorescence response of a pH sensitive probe, thus yielding a maximum emission enhancement factor of 400 upon acidification. Furthermore, quantum chemical calculations were used to reproduce the experimental trends of reduction potentials, excited state energies, and ET driving forces within the framework of linear free energy relationships (LFER). Such LFERs should be suitable to semi-empirically predict ET driving forces with an average unsigned error of 0.03 eV, consequently allowing for the computational prescreening of substituent combinations to best match the donor potential of a given cation receptor. Within the scaffold of the triarylpyrazoline platform, the outlined differential tuning of the electron transfer parameters should be applicable to a broad range of cation receptors for designing PET sensors with maximized contrast ratios.

Selective fluorescent probes for live-cell monitoring of sulphide

“…We selected 1,3,5-triaryl-2-pyrazoline as the first fluorophore template because its fluorescence is sensitive to the electronic changes of the substituted aromatic groups 16 . During synthesis of the probe, we inadvertently obtained 1,3,5-triaryl-pyrazole because of a required oxidation step (Fig.…”

“…The development of innovative fluorescent imaging probes has revolutionized cell biology, allowing localization and dynamic monitoring of cellular metabolite and inorganic ion pools 15,16,[24][25][26][27][28][29] . A significant bottleneck in the emerging field of H 2 S/aqueous sulphide signalling is the absence of technology for effective in vivo detection and imaging, a problem that is exacerbated by the high intracellular thiol concentration.…”

Molecular Logic Gates and Luminescent Sensors Based on Photoinduced Electron Transfer

“…A newer example bearing a similar bisimide structure is 2 [27]. Fahrni's compound 3 [28,29] switches "on" its emission when the aniline unit picks up H þ . The structure and function of 3 has precedents [30,31] which were designed to respond to Na þ and Ca 2þ , but were tested for their response to H þ as well.…”

Thiophene‐Inserted Aryl–Dicyanovinyl Compounds: The Second Generation of Fluorescent Molecular Rotors with Significantly Redshifted Emission and Large Stokes Shift

“…[1] Well-known molecular rotors are 1-(dicyanovinyl)-4-(dimethylamino)benzene (1) and 9-(dicyanovinyl)julolidine (2, DCVJ; Scheme 1). [1] DCVJ and a few other rotors, based on different mechanisms, [12][13][14] have been used to measure the viscosity or shear stress of a microenvironment, [1] reaction medium, [15] or intracellular plasma. [16,17] However, the conventional aryl-dicyanovinyl molecular rotors for viscosity sensing [for example, DCVJ (2)] suffer from fundamental photophysical drawbacks, such as short absorption/emission wavelengths (465/503 nm, respectively) [ and a small Stokes shift (38 nm).…”

“…[14] Porphyrin-based rotors have been reported, but the rotors are synthetically demanding. [12,16] Therefore, simple rotors with redshifted excitation/emission and a large Stokes shift are highly desired as alternatives to DCVJ for molecular viscosity sensing.…”