A family of easily accessible light-activated hydrazone switches has been developed having thermal half-lives of up to 2700 years! Structure–property analysis shows that replacing the rotor pyridyl group of our typical hydrazone switch with a phenyl one leads to the long-lived negative photochromic compounds. The switching properties of the hydrazones in both toluene and DMSO were assessed offering insights into the kinetics and thermodynamics of the switching process.

A novel visible-light activated azo-BF2 switch possessing a phenanthridinyl π-system has been synthesized, and its switching properties have been characterized as a function of concentration. The switch self-aggregates through π–π interactions, and the degree of aggregation modulates the Z → E thermal isomerization rate. This property allows for the active tuning of the thermal relaxation half-life of the same switch from seconds to days.

Azo-BF2 switches 1 and 2 with their extended phenanthridinyl π-system exhibit red-light fluorescence whose intensity can be photomodulated using visible-light. The para-methoxy group in 2 leads to a bathochromic shift in the emission band, pushing its tail further to the near infrared region. This group also changes the isomerization properties in 2, as it does not display the concentration-dependent isomerization rate change observed in 1, most likely because of a change in mechanism from rotation to inversion, and weaker π−π interaction in the system.Download high-res image (171KB)Download full-size image

A negative feedback loop that relies on the coordination-coupled deprotonation (CCD) of a hydrazone switch has been developed. Above a particular threshold of zinc(II), CCD releases enough protons to the environment to trigger a cascade of reactions that yield an imine. This imine sequesters the excess of zinc(II) from the hydrazone switch, hence lowering the effective amount of protons, and switching the cascade reactions “OFF”, thus establishing the negative feedback loop.

Proton relay plays an important role in many biocatalytic pathways. In order to mimic such processes in the context of molecular switches, we developed coordination-coupled deprotonation (CCD) driven signaling and signal enhancement sequences. This was accomplished by using the zinc(II)-initiated CCD of a hydrazone switch to instigate an acid catalyzed imine bond hydrolysis that separates a quencher from a fluorophore thus leading to emission amplification. Because CCD is a reversible process, we were able to show that the catalysis can be regulated and turned “on” and “off” using a metalation/demetalation cycle.

A serendipitous discovery has led to a new hydrazone-based low molecular weight fluorescent super-hydrogelator. The gelation and emission properties can be switched “ON” and “OFF” using pH, enabling the sensing of biogenic amines emanating from spoiled cod.

The hydrazone functional group has been extensively studied and used in the context of supramolecular chemistry. Its pervasiveness and versatility can be attributed to its ease of synthesis, modularity, and most importantly unique structural properties, which enable its integration in different applications. This review provides an overview of the utilization of hydrazones in three supramolecular chemistry related areas: molecular switches, metallo-assemblies and sensors. These topics were chosen because they highlight the diversity of hydrazones, and emphasize their uniqueness vis-à-vis the imine functional group. Discussion entails (i) chemical and light activated switching of hydrazones, and how this can be used in controlling the properties of self-assembled systems, (ii) the use of hydrazones in the formation of dynamic and stimuli responsive metallogrids, and (iii) the use of hydrazones in detecting metal cations (Zn2+, Cu2+, Hg2+, etc.), anions (F−, CN−, P2O74−, etc.) and neutral molecules (amines, water, Cys, etc.).

It should be noted though that designing structurally simple switches cannot be an end goal by itself! Therefore, we showed that our molecules can be used in applications that are beyond a simple molecular switching event (i.e., the control of the photophysical properties of liquid crystals and multistep switching cascades). While focusing on these switches, we discovered that the hydrazones can be easily transformed, using straightforward one-step reactions, into visible light activated azo switches, and two different families of fluorophores that can be used in sensing applications. These findings demonstrate that our approach of developing simple systems for sophisticated functions is not limited to the field of molecular switches and machines but can also encompass other adaptive materials.

Molecular switches and machines that are powered by acid–base reactions are susceptible to low switching cycles because of the concomitant formation of waste products during their operation. Here, we demonstrate the fast, efficient, and reversible modulation of a hydrazone switch in methanol using a visible-light activated photoacid, with no generation of side products, high conversion rates (>95%), and no loss of activity over 100 cycles. TEG functionalization of the hydrazone switch allows for the process to be carried with high conversion (>90%) in water as well.

A triazolopyridinium salt chemodosimeter has been developed that displays a 60-fold enhancement in fluorescence upon reaction with cyanide. The novel, fast, selective and sensitive reaction-based indicator relies on the pseudopericyclic ring opening of the bridgehead nitrogen-containing detector.

The extra H-bond in a bipyridyl-functionalized hydrazone rotary switch slows down its Z→E isomerization rate by 2 orders of magnitude (k = (3.5 ± 0.2) × 10–6 s–1). The coordination of Zn2+ with the bipyridyl subgroup simultaneously ‘unlocks’ this H-bond and accelerates the isomerization rate by at least 6 orders of magnitude (k > 6.9 s–1). This coordination-regulated kinetic control could open the way to molecular timers that can be used in guiding temporal events.

Two [1,2,3]triazolo[1,5-a]pyridinium salts have been prepared via a novel Cu(II)-mediated oxidative cyclization reaction. Both water soluble compounds exhibit broad-range fluorescence emission with huge Stokes shifts as well as color tunability.

Here we report the synthesis and characterization of a BF2–azo complex that can be induced to isomerize without the need of deleterious UV light. The complexation of the azo group with BF2, coupled with the extended conjugation of the N═N π-electrons, increases the energy of the n−π* transitions and introduces new π-nonbonding (πnb) to π* transitions that dominate the visible region. The well separated πnb–π* transitions of the trans and cis isomers enable the efficient switching of the system by using only visible light. The complexation also leads to a slow cis → trans thermal relaxation rate (t1/2 = 12.5 h). Theoretical calculations indicate that the absorption bands in the visible range can be tuned using different Lewis acids, opening the way to a conceptually new strategy for the manipulation of azo compounds using only visible light.

A new family of BF2–hydrazone complexes was developed that exhibit enhanced emission in the solid-state. The modularity of the systems enabled their structure–property analysis, which showed that the solid-state fluorescence quantum yield is dependent on the molecule's planarity, dipole moment and number of π–π interactions it forms. One of the BF2–hydrazone complexes was easily transformed into a solid-state acid/base sensor.

A “V”-shaped Hammett plot shows that resonance-assisted hydrogen bonding does not dictate the strength of the intramolecular hydrogen bond in the E isomers of hydrazone-based switches because it involves an aromatic pyridyl ring.

Crystal structures of η5-coordinated polymers of cyclopentadienyl lithium (CpLi) derivatives are rare. Herein we describe the solid-state characterization of the base-free supersandwich of benzyl cyclopentadienyl lithium ([BnCp–Li]∞). The self-assembled polymer has the shortest mean Li–Cp (2.286 Å) and Li–Cpcentroid (1.948 Å) bond distances of known mono-substituted CpLi compounds.

Two intramolecularly hydrogen-bonded arylhydrazone (aryl = phenyl or naphthyl) molecular switches have been synthesized, and their full and reversible switching between the E and Z configurations have been demonstrated. These chemically controlled configurational rotary switches exist primarily as the E isomer at equilibrium and can be switched to the protonated Z configuration (Z-H+) by the addition of trifluoroacetic acid. The protonation of the pyridine moiety in the switch induces a rotation around the hydrazone C═N double bond, leading to isomerization. Treating Z-H+ with base (K2CO3) yields a mixture of E and “metastable” Z isomers. The latter thermally equilibrates to reinstate the initial isomer ratio. The rate of the Z → E isomerization process showed small changes as a function of solvent polarity, indicating that the isomerization might be going through the inversion mechanism (nonpolar transition state). However, the plot of the logarithm of the rate constant k vs the Dimroth parameter (ET) gave a linear fit, demonstrating the involvement of a polar transition state (rotation mechanism). These two seemingly contradicting kinetic data were not enough to determine whether the isomerization mechanism goes through the rotation or inversion pathways. The highly negative entropy values obtained for both the forward (E → Z-H+) and backward (Z → E) processes strongly suggest that the isomerization involves a polarized transition state that is highly organized (possibly involving a high degree of solvent organization), and hence it proceeds via a rotation mechanism as opposed to inversion. Computations of the Z ↔ E isomerization using density functional theory (DFT) at the M06/cc-pVTZ level and natural bond orbital (NBO) wave function analyses have shown that the favorable isomerization mechanism in these hydrogen-bonded systems is hydrazone–azo tautomerization followed by rotation around a C–N single bond, as opposed to the more common rotation mechanism around the C═N double bond.

A hydrazone-based rotary switch, having a quinolinyl stator and a pyridine ring as part of the rotor, can be induced using pH to undergo a four-step switching sequence. This process yields three stable isomers and a fourth “metastable” one that can all be addressed separately based on the sequence of acid and base added. The switching process proceeds via conformational and/or configurational changes, allowing the molecule to rotate around two different axles.

The replacement of one of the carbonyl groups in a 1,2,3-triketone-2-naphthylhydrazone with a pyridine ring yields an original molecular switch that can be switched fully, effectively, and reversibly between the E and Z configurations. This hydrazone-based, pH-controlled, molecular switch is the first example of a chemically controlled configurational rotary switch. The bistable switch exists primarily (97%) as the E configuration in solution and can be converted quantitatively to the Z-H+ configuration upon treatment with trifluoroacetic acid. When Z-H+ is passed over a plug of K2CO3, the “metastable” Z configuration is observed using 1H NMR spectroscopy, which thermally equilibrates to give back the E configuration. The rate of this process is dependent on the polarity of the solvent, indicating that the E/Z isomerization takes place via a rotation around the hydrazone C═N bond.

Increasing the electron density in BF2-coodinated azo compounds through para-substitution leads to a bathochromic shift in their activation wavelength. When the substituent is dimethyl amine, or the like, the trans/cis isomerization process can be efficiently modulated using near infrared light. The electron donating capability of the substituent also controls the hydrolysis half-life of the switch in aqueous solution, which is drastically longer for the cis isomer, while the BF2-coodination prevents reduction by glutathione.

The hydrazone functional group has been extensively studied and used in the context of supramolecular chemistry. Its pervasiveness and versatility can be attributed to its ease of synthesis, modularity, and most importantly unique structural properties, which enable its integration in different applications. This review provides an overview of the utilization of hydrazones in three supramolecular chemistry related areas: molecular switches, metallo-assemblies and sensors. These topics were chosen because they highlight the diversity of hydrazones, and emphasize their uniqueness vis-à-vis the imine functional group. Discussion entails (i) chemical and light activated switching of hydrazones, and how this can be used in controlling the properties of self-assembled systems, (ii) the use of hydrazones in the formation of dynamic and stimuli responsive metallogrids, and (iii) the use of hydrazones in detecting metal cations (Zn2+, Cu2+, Hg2+, etc.), anions (F−, CN−, P2O74−, etc.) and neutral molecules (amines, water, Cys, etc.).

A new family of BF2–hydrazone complexes was developed that exhibit enhanced emission in the solid-state. The modularity of the systems enabled their structure–property analysis, which showed that the solid-state fluorescence quantum yield is dependent on the molecule's planarity, dipole moment and number of π–π interactions it forms. One of the BF2–hydrazone complexes was easily transformed into a solid-state acid/base sensor.

A serendipitous discovery has led to a new hydrazone-based low molecular weight fluorescent super-hydrogelator. The gelation and emission properties can be switched “ON” and “OFF” using pH, enabling the sensing of biogenic amines emanating from spoiled cod.

Two [1,2,3]triazolo[1,5-a]pyridinium salts have been prepared via a novel Cu(II)-mediated oxidative cyclization reaction. Both water soluble compounds exhibit broad-range fluorescence emission with huge Stokes shifts as well as color tunability.

Proton relay plays an important role in many biocatalytic pathways. In order to mimic such processes in the context of molecular switches, we developed coordination-coupled deprotonation (CCD) driven signaling and signal enhancement sequences. This was accomplished by using the zinc(II)-initiated CCD of a hydrazone switch to instigate an acid catalyzed imine bond hydrolysis that separates a quencher from a fluorophore thus leading to emission amplification. Because CCD is a reversible process, we were able to show that the catalysis can be regulated and turned “on” and “off” using a metalation/demetalation cycle.

A “V”-shaped Hammett plot shows that resonance-assisted hydrogen bonding does not dictate the strength of the intramolecular hydrogen bond in the E isomers of hydrazone-based switches because it involves an aromatic pyridyl ring.