Photocontrol of GTPase Cycle and Multimerization of the Small G-Protein H-Ras using Photochromic Azobenzene Derivatives

Ras is a small G protein known as a central regulator of cellular signal transduction that induces processes, such as cell division, transcription. The hypervariable region (HVR) is one of the functional parts of this G protein, which induces multimerization and interaction between Ras and the plasma membrane. We introduced two highly different in polarity photochromic SH group-reactive azobenzene derivatives, N-4-phenyl-azophenyl maleimide (PAM) and 4-chloroacetoamido-4-sulfo-azobenzene (CASAB), into three cysteine residues in HVR to control Ras GTPase using light. PAM stoichiometrically reacted with the SH group of cysteine residues and induced multimerization. The mutants modified with PAM exhibited reversible changes in GTPase activity accelerated by the guanine nucleotide exchange factor and GTPase activating protein and multimerization accompanied by cis- and trans-photoisomerization upon ultraviolet and visible light irradiation. CASAB was incorporated into two of the three cysteine residues in HVR but did not induce multimerization. The H-Ras GTPase modified with CASAB was photo controlled more effectively than PAM-H-Ras. In this study, we revealed that the incorporation of azobenzene derivatives into the functional site of HVR enables photo reversible control of Ras function. Our findings may contribute to the development of a method to control functional biomolecules with physiologically important roles.

Sulfur and azobenzenes, a profitable liaison: straightforward synthesis of photoswitchable thioglycosides with tunable properties

Azobenzene photoswitches are valuable tools for controlling properties of molecular systems with light. In particular, we have been investigating azobenzene glycoconjugates to probe carbohydrate-protein interactions and also to design photoresponsive glycomacrocycles with modulable chiroptical and physicochemical properties. To date, direct conjugation of glycosides to azobenzenes was performed by reactions providing target compounds in limited yields. We therefore sought for a more effective and reliable coupling method. In this paper, we report on a straightforward thioarylation of azobenzene derivatives with glycosyl thiols as well as other thiol substrates, increasing the scope of azobenzene conjugation. Importantly, red-shifted azoswitches that can be addressed with visible light were easily functionalized and challenging unsymmetrical conjugates were prepared in good yields via sequential or one pot procedures. In addition, we took advantage of the presence of the sulfide bridge to tune both photochromic and thermal relaxation properties of the core azobenzene via sulfur oxidation. Based on our photochemical investigations, we finally demonstrated orthogonal three-state photoswitching in mixtures containing two distinct azobenzene thioglycosides.

Sulfur and azobenzenes, a profitable liaison: straightforward synthesis of photoswitchable thioglycosides with tunable properties

Azobenzene photoswitches are valuable tools for controlling properties of molecular systems with light. In particular, we have been investigating azobenzene glycoconjugates to probe carbohydrate-protein interactions and also to design photoresponsive glycomacrocycles with modulable chiroptical and physicochemical properties. To date, direct conjugation of glycosides to azobenzenes was performed by reactions providing target compounds in limited yields. We therefore sought for a more effective and reliable coupling method. In this paper, we report on a straightforward thioarylation of azobenzene derivatives with glycosyl thiols as well as other thiol substrates, increasing the scope of azobenzene conjugation. Importantly, red-shifted azoswitches that can be addressed with visible light were easily functionalized and challenging unsymmetrical conjugates were prepared in good yields via sequential or one pot procedures. In addition, we took advantage of the presence of the sulfide bridge to tune both photochromic and thermal relaxation properties of the core azobenzene via sulfur oxidation. Based on our photochemical investigations, we finally demonstrated orthogonal three-state photoswitching in mixtures containing two distinct azobenzene thioglycosides.

Photocontrolled Azo-Containing Adhesives

The photoisomerization of azobenzene (Azo) in system can induce changes of adhesion. Using this feature, some significant breakthroughs have been achieved in distinct adhesive systems from small molecular to polymer to supramolecular. Although the mechanisms vary from different situations, photoisomerization and photothermal effect of azobenzene under different irradiation always play significant role in the switch of the adhesion strength. By utilizing these features, some adhesive systems have illustrated promising and competitive performance. This review will concentrate on these achievements and advantages of photocontrolled adhesives based on azobenzene derivatives which are classified by photocontrolled mechanism. Furthermore, we also give some consideration to the future development of photocontrolled adhesives.

Supramolecular Gels Based on Azobenzene Derivatives

In the past years, azobenzene, as a common photoreactive group, has been widely used in intelligent photocontrolled supramolecular gels. In the field of biomedicine, a few supramolecular hydrogels based on azobenzene are regarded as carriers with low damage and high control in vivo due to their advantages in light response. In the environmental field, some hydrogels can also adsorb pollutants under the control of light through the interaction between host and guest. At the same time, supramolecular hydrogels based on azobenzene with multiple stimulus responses have been studied. It is difficult for most supramolecular organogels to have multiple stimulus responses simultaneously and the preparation conditions are also more complex. In this paper, I have summarized the latest research results of supramolecular hydrogels and organogels based on azobenzene in recent years so that researchers can have a deeper understanding of the preparation methods, properties and application of the supramolecular gels containing azobenzene.

Impact of Van der Waals interactions on structural and nonlinear optical properties of azobenzene switches

<div> <div> <div> <p>The geometrical structures, relative Z-E energies, and second-order nonlinear responses of a collection of azobenzene molecules symmetrically substituted in meta- position with functional groups of different bulkiness are investigated using various ab initio and DFT levels of approximation. We show that RI-MP2 and RI-CC2 approximations provide very similar geometries and relative energies and evidence that London dispersion interactions existing between bulky meta-substituents stabilize the Z con- former. The !B97-X-D exchange-correlation functional provides an accurate description of these effects and gives a good account of the nonlinear optical response of the molecules. We show that density functional approximations should include no less than 50% of Hartree-Fock exchange to provide accurate hyperpolarizabilities. A property-structure analysis of the azobenzene derivatives reveals that the main contribution to the first hyperpolarizability comes from the azo bond, but phenyl meso-substituents can enhance it.</p> </div> </div> </div>

Impact of Van der Waals interactions on structural and nonlinear optical properties of azobenzene switches

<div> <div> <div> <p>The geometrical structures, relative Z-E energies, and second-order nonlinear responses of a collection of azobenzene molecules symmetrically substituted in meta- position with functional groups of different bulkiness are investigated using various ab initio and DFT levels of approximation. We show that RI-MP2 and RI-CC2 approximations provide very similar geometries and relative energies and evidence that London dispersion interactions existing between bulky meta-substituents stabilize the Z con- former. The !B97-X-D exchange-correlation functional provides an accurate description of these effects and gives a good account of the nonlinear optical response of the molecules. We show that density functional approximations should include no less than 50% of Hartree-Fock exchange to provide accurate hyperpolarizabilities. A property-structure analysis of the azobenzene derivatives reveals that the main contribution to the first hyperpolarizability comes from the azo bond, but phenyl meso-substituents can enhance it.</p> </div> </div> </div>

Study of Aggregation Behavior of Predesigned Azobenzene-Cholesteryl Derivatives in Deep Eutectic Solvents

Structurally isomeric cholesteryl-appended azobenzene derivatives (azo-1 to azo-5) with various substituents, such as H/unsubstituted, ether, ester, and nitro at the terminal position of azobenzene units were designed, and synthesized. The gelation ability and aggregation behavior of the above synthesized azobenzene-cholesteryl derivatives in deep eutectic solvents (DES) such as Zinc Chloride: Ethylene Glycol (Zn:EG), Choline Chloride: EG (Ch:EG), Choline Chloride: Urea (Ch: Urea), and Choline Chloride: Glycine (Ch: Gly) were studied. The results revealed that all the azo derivatives formed semi-transparent and strong/hard eutectic gels in at least one DES except azo-4 which formed gel in two DES. The morphological analyses by scanning electron microscopy (SEM) exhibited entangled dense fibrous, flowers, and sheet-like textures, depending on the nature of DES as well as azo derivatives. Like all azobenzene-based organo-gelators, UV-triggered gel-to-sol transition was expected for these eutectic gels. However, these eutectic gels did not undergo the gel-to-sol transition under UV irradiation. This could be due to the hardness of the gel, which arrests the structural transformation from trans-to-cis during photolysis. It was further confirmed by absorption profiles of before and after irradiation of eutectic gels. Regarding application, an attempt has been made to use eutectic gels as a template for the synthesis of nanomaterials and the results revealed that the azo-4 gel can be used to prepare aggregated highly dense nanorods of copper chloride.