Highly Fluorescent Flavins: Rational Molecular Design for Quenching Protection Based on Repulsive and Attractive Control of Molecular Alignment

Abstract

Unprecedented intense fluorescent emission was observed for a variety of flavin compounds bearing a perpendicular cyclic imide moiety at the C7 position of an isoalloxazine platform. A series of alloxan-substituted flavins was prepared selectively by reduction of the corresponding N-aryl-2-nitro-5-alkoxyanilines with zinc dust and subsequent reaction with alloxan monohydrate in the presence of boric acid. Analogues bearing oxazolidine-2,4-dione functionality were obtained on methylation of the alloxan-substituted flavins with methyl iodide and subsequent rearrangement in the presence of an inorganic base. The flavin compounds exhibit intense white-green fluorescent emission in the solution state under UV excitation at 298 K, with emission efficiencies Φ298 K greater than 0.55 in CH3 CN, which are higher than the values for all reported flavin compounds under similar conditions. The highest Φ298 K value of 0.70 was obtained in CH3 CN for isoalloxazine bearing C7-alloxan and N10-2,6-diisopropylphenyl groups. The temperature dependence of the emission intensities indicates that the pronounced emission properties at 298 K are attributable to the highly heat resistant properties towards emission decay with increasing temperature. Mechanistic studies, including X-ray diffraction analysis, revealed that the good emission properties and high heat resistance of the alloxan-substituted flavins are due to a synergetic effect of the associative nature of the C7-alloxan unit and the repulsive nature of the perpendicular bulky substituents at the C7 and N10 positions.

Fluorescent Crystals of Zwitterionic Imidazolium Pyridinolates: A Rational Design for Solid‐State Emission Based on the Twisting Control of Proemissive N‐Aryl Imidazolium Platforms

“…Mechanistic investigations revealed that the present intense solid‐state emission arises from a structure‐specific preference for the planar conformation and multiplicity in hydrogen bonding fixation of the molecular unit to achieve enhanced energy transition probability and heat‐resistance properties in the crystalline state. This work clearly demonstrates the importance of repulsive and attractive control for restriction of molecular rotation to achieve intense solid‐state emission. Research is currently underway to apply this principle to the development of new light‐emitting functional materials.…”

“…As part of a program to create highly fluorescent and phosphorescent materials based on the three‐dimensional synthetic alteration of less‐ or proemissive platforms, we investigated the emission properties of a series of zwitterionic imidazolium N ‐arenolates (Scheme ),, and found that 2‐pyridin‐3‐olate isomer 1 exhibits intense solid‐state fluorescence exclusively in the crystalline state at ambient temperature. All the other zwitterionic analogues with various functionalities are non‐ or less emissive under similar conditions.…”

Lightening flavin by amination for fluorescent sensing

“…Apart from those specially designed FL-based fluorescent sensors, 35–39 substitution on the benzene ring was shown to efficiently modulate the photophysical properties and many artificial FLs, 41 including isopropyl-, 42 bromo-, 27,31,43 iodo-, 19 trifluoromethyl-, 43 amino-, 41,44–48 fluoro- 40,49,50 and methyl-modified 51,52 FLs were designed as fluorescent sensors or photosensitizers. 18–53 AmFLs are an important group within the large family of FLs and a number of AmFLs, such as roseoflavin, etc. , exist in organisms and possess antibacterial, anticancer and antiviral activities.…”

Tuning the Photophysical Properties of Flavins by Attaching an Aryl Moiety via Direct C–C Bond Coupling

“…A detailed review of the literature indicated that this oversight is due to a lack of a general procedure for installing an aryl group in the benzene ring of flavins. With one nongeneral exception, the synthesis of C7- and C8-arylated flavins has been accomplished by means of the sequential cyclization of aniline derivatives (Scheme a) . It should be noted that the step-by-step construction of a flavin moiety is not effective because it requires a specific approach for each derivative and is characterized by a limited scope.…”