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The application of merocyanine photoacids has been previously largely limited to neutral and acidic pH values. Here we introduce a new merocyanine photoacid with superior pH switching qualities. By increasing the pKa in the dark (pKadark) and the solubility we increased the reversible visible light induced pH jump to 3.5 units. Moreover, it is the first demonstration of a merocyanine photoacid able to generate a significant pH drop from a basic (pH 8.3) to an acidic (pH 5.2) environment.

Molecular photoswitches capable of generating precise pH changes will allow pH-dependent processes to be controlled remotely and noninvasively with light. We introduce a series of new merocyanine photoswitches, which deliver reversible bulk pH changes up to 3.2 pH units (pH 6.5 to pH 3.3) upon irradiation with 450 nm light, displaying tunable and predictable timescales for thermal recovery. We present models to show that the key parameters for optimizing the bulk pH changes are measurable: the solubility of the photoswitch, the acidity of the merocyanine form, the thermal equilibrium position between the spiropyran and the merocyanine isomers, and the increased acidity under visible light irradiation. Using ultrafast transient absorption spectroscopy, we determined the quantum yields for the ring-closing reaction and found that the lifetimes of the transient cis-merocyanine isomers ranged from 30 to 550 ns. Quantum yields did not appear to be a limitation for bulk pH switching. The models we present use experimentally determined parameters and are, in principle, able to predict the change in pH obtained for any related merocyanine photoacid.

Green-to-blue triplet-triplet annihilation photon upconversion using the well-studied upconversion pair 9,10-diphenylanthracene (DPA)/platinum octaethylporphyrin (PtOEP) is used to reversibly drive the photoisomerization of diarylethene (DAE) photoswitches using visible light. By carefully selecting the kinetic and spectral properties of the molecular system as well as the experimental geometry, a single green light source can be used to selectively trigger both the ring-opening and the ring-closing reactions, whilst also inducing fluorescence from the closed colored isomer that can be used as a readout to monitor the isomerization process in situ. The upconversion solution and the DAE solution are kept physically separated, allowing to characterize them both concomitantly and individually without further separation processes. The ring-closing reaction using upconverted photons is quantified and compared to the efficiency of direct isomerization using ultraviolet light.

Self-assembled peptide nanostructures with stimuli-responsive features are promising as functional materials. Despite extensive research efforts, water-soluble supramolecular constructs that can interact with lipid membranes in a controllable way are still challenging to achieve. Here, we have employed a short membrane anchor protein motif (

Precisely modulated photoluminescence (PL) with external control is highly demanded in material and biological sciences. However, it is challenging to switch the PL

A water soluble diarylethene (DAE) derivative that displays exceptionally intense fluorescence from the colorless open form has been synthesized and characterized using UV/vis spectroscopy and fluorescence microscopy. We show that the bright emission from the open form can be rapidly switched using amplitude modulated red light, that is, by light at wavelengths longer than those absorbed by the fluorescent species. This is highly appealing in any context where undesired background fluorescence disturbs the measurement, e.g., the autofluorescence commonly observed in fluorescence microscopy. We show that this scheme is conveniently applicable using lock-in detection, and that robust amplitude modulation of the probe fluorescence is indeed possible also in cell studies using fluorescence microscopy., A water soluble diarylethene derivative displaying exceptionally bright fluorescence in the open isomeric form has been used for emission amplitude-modulation. We apply this scheme in fluorescence microscopy, aiming to suppress undesired background.

Journal of materials chemistry / C 10(42), 15833-15842 (2022). doi:10.1039/D2TC03582K, Published by Royal Society Chemistry, London [u.a.]

A photoswitchable DFG-out kinase inhibitor has been developed. The activity of the inhibitor can efficiently be regulated by light in both enzymatic and living cell assays.

Molecular photoswitches capable of generating pH changes with precision will allow pH-dependent processes to be controlled remotely and non-invasively with light. We introduce a series of new spiropyran photoswitches, delivering reversible bulk pH changes up to 3.2 pH units (pH 6.5 to pH 3.3) upon irradiation with 450 nm light, displaying tunable and predictable timescales for thermal recovery. We present models to show that the key parameters for optimizing the bulk pH changes are measurable: the solubility of the photoswitch, the acidity of the merocyanine form influenced by the thermal equilibrium position between the spiropyran and the merocyanine isomers, and the increased acidity under visible light irradiation. Using ultrafast transient absorption spectroscopy, we determine quantum yields for the ring closing reaction and observe the lifetime of the transient cis-merocyanine isomer ranging from 30 to 550 ns. Quantum yields did not appear to be a limitation of bulk pH switching. The models we present use experimentally determined parameters and are, in principle, able to predict the change in pH obtained for any related spiropyran photoacid.

Molecular photoswitches capable of generating pH changes with precision will allow pH-dependent processes to be controlled remotely and non-invasively with light. We introduce a series of new spiropyran photoswitches, delivering reversible bulk pH changes up to 3.2 pH units (pH 6.5 to pH 3.3) upon irradiation with 450 nm light, displaying tunable and predictable timescales for thermal recovery. We present models to show that the key parameters for optimizing the bulk pH changes are measurable: the solubility of the photoswitch, the acidity of the merocyanine form influenced by the thermal equilibrium position between the spiropyran and the merocyanine isomers, and the increased acidity under visible light irradiation. Using ultrafast transient absorption spectroscopy, we determine quantum yields for the ring closing reaction and observe the lifetime of the transient cis-merocyanine isomer ranging from 30 to 550 ns. Quantum yields did not appear to be a limitation of bulk pH switching. The models we present use experimentally determined parameters and are, in principle, able to predict the change in pH obtained for any related spiropyran photoacid.

The reaction of 4,4′,4′′,4′′′-(ethene-1,1,2,2-tetrayl)tetraaniline with 2-pyridinecarboxaldehyde and iron(II) chloride resulted, after aqueous workup, in the diastereoselective formation of an [Fe 2 L 3 ] 4+ triple-stranded helicate structure, irrespective of the stoichiometry employed. The helicate structure was characterized in solution by multinuclear NMR spectroscopy, and in the solid state by single-crystal X-ray crystallography. The reaction of iron(II) tetrafluoroborate or iron(II) bistriflimide with the tetraaniline and 2-pyridinecarboxaldehyde allowed the formation of an [Fe 8 L 6 ] 16+ cube when the appropriate stoichiometry was used, but these structures were unstable with respect to hydrolysis. The pendant amine groups on the helicate can be functionalized by reaction with acid chlorides or anhydrides, and the resulting functionalized tetraphenylethene (TPE) units were isolated by the reaction of the helicate with tris(2-aminoethyl)amine. The emission properties of the TPE units were studied in THF/water mixtures, and they were found by dynamic light scattering to self-assemble into large (av. diameter 250 nm) structures.

The underlying role that many kinases play in complex cellular pathways as well as disease remains unclear. To better understand the role that kinases play in both health and disease states, the use of light as an external stimulus to modulate kinase activity with high spatiotemporal resolution has gained increasing interest over the years. Herein we highlight the progress made towards the development of light-responsive kinase enzymes and small molecule inhibitors. In these examples, photolabile caging groups and photoswitchable entities have been utilised to modulate either kinase activation or inhibition in a light-controlled manner.

On-command changes in the emission color of functional materials is a sought-after property in many contexts. Of particular interest are systems using light as the external trigger to induce the color changes. Here we report on a tri-component cocktail consisting of a fluorescent donor molecule and two photochromic acceptor molecules encapsulated in polymer micelles and we show that the color of the emitted fluorescence can be continuously changed from blue-to-green and from blue-to-red upon selective light-induced isomerization of the photochromic acceptors to the fluorescent forms. Interestingly, isomerization of both acceptors to different degrees allows for the generation of all emission colors within the red-green-blue (RGB) color system. The function relies on orthogonally controlled FRET reactions between the blue emitting donor and the green and red emitting acceptors, respectively., Stimuli-responsive multicolor luminescent materials typically react on external triggers of physical nature, but photonically controlled systems which allow for remote operation were not realized. Here the authors use light as the stimulus of a responsive luminescent material which eliminates the need for physical access.

The combination of two two-photon-induced processes in a Förster resonance energy transfer (FRET)-operated photochromic fluorene-dithienylethene dyad lays the foundation for the observation of a quartic dependence of the fluorescence signal on the excitation light intensity. While this photophysical behavior is predicted for a four-photon absorbing dye, the herein proposed approach opens the way to use two-photon absorbing dyes, reaching the same performance. Hence, the spatial resolution limit, being a critical parameter for applications in fluorescence imaging or data storage with common two-photon absorbing dyes, is dramatically improved.

International audience; The binding of donor-acceptor Stenhouse adducts (DASAs) bearing hydrogenbond recognition groups by Hamilton-type receptors significantly influenced their photoswitching properties by altering thermal barriers to isomerization. The thermal barrier between the most stable linear isomer and the photo-generated isomer is lowered on binding to a receptor, and this barrier is crucial for switching properties. The thermal isomerization was shown to proceed via a stepwise linear-enol-keto mechanism in DMSO where the barrier to tautomerisation is within 2 kJ•mol-1 of that of the rate-determining step, which may be important for analyzing switching properties.

A molecular cocktail containing two photochromic diarylethene derivatives that displays multicolor emission spanning blue-green to orange in a color-correlated fashion has been devised. The function does not rely on excited state communication such as energy transfer reactions, which is the typical case for similar systems. Instead, harnessing the intrinsic fluorescent and photochromic properties of the two individual diarylethene derivatives run in parallel is enough to realize the color changes. This offers an extremely flexible situation as for the choice of the fluorophores and their respective concentrations. The function is conveniently demonstrated in bulk solution at μM concentrations, where a single light source serves as the color changing stimulus.

REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase that is required for development of multiple human tissues, but which is also an important contributor to human cancers. RET activation through rearrangement or point mutations occurs in thyroid and lung cancers. Furthermore, activation of wild type RET is an increasingly recognized mechanism promoting tumor growth and dissemination of a much broader group of cancers. RET is therefore an attractive therapeutic target for small-molecule kinase inhibitors. Non-invasive control of RET signaling with light offers the promise of unveiling its complex spatiotemporal dynamics in vivo. In this work, photoswitchable DFG-out RET kinase inhibitors based on heterocycle-derived azobenzenes were developed, enabling photonic control of RET activity. Based on the binding mode of DFG-out kinase inhibitors and using RET kinase as the test model, we developed a photoswitchable inhibitor with a quinoline "head" constituting the azoheteroarene. This azo compound was further modified by three different strategies to increase the difference in biological activity between the E-isomer and the light enriched Z-isomer. Stilbene-based derivatives were used as model compounds to guide in the selection of substituents that could eventually be introduced to the corresponding azo compounds. The most promising quinoline-based compound showed more than a 15-fold difference in bioactivity between the two isomers in a biochemical assay. However, the same compound showed a decreased Z/E (IC

The photo- and acidochromic properties of a new generation norbornadiene derivative have been harnessed for the realization of a three-input keypad lock, where a specific sequence of inputs induces a unique output. Reversible quadricyclane/norbornadiene photoisomerization is reported, and this rare feature allows the first example of a norbornadiene-based molecular logic system. The function of this system is clearly rationalized in terms of the interconversion scheme and the absorption spectra of the involved species.

The idea of using molecules in the context of information security has sparked the interest of researchers from many scientific disciplines. This is clearly manifested in the diversity of the molecular platforms and the analytical techniques used for this purpose, some of which we highlight in this Tutorial Review. Moreover, those molecular systems can be used to emulate a broad spectrum of security measures. For a long time, molecular keypad locks enjoyed a clear preference and the review starts off with a description of how these devices developed. In the last few years, however, the field has evolved into something larger. Examples include more complex authentication protocols (multi-factor authentication and one-time passwords), the recognition of erroneous procedures in data transmission (parity devices), as well as steganographic and cryptographic protection.

Photochromic molecules undergo reversible isomerization upon irradiation with light at different wavelengths, a process that can alter their physical and chemical properties. For instance, dihydropyrene (DHP) is a deep-colored compound that isomerizes to light-brown cyclophanediene (CPD) upon irradiation with visible light. CPD can then isomerize back to DHP upon irradiation with UV light or thermally in the dark. Conversion between DHP and CPD is thought to proceed via a biradical intermediate; bimolecular events involving this unstable intermediate thus result in rapid decomposition and poor cycling performance. Here, we show that the reversible isomerization of DHP can be stabilized upon confinement within a (PdIIL4)-L-6 coordination cage. By protecting this reactive intermediate using the cage, each isomerization reaction proceeds to higher yield, which significantly decreases the fatigue experienced by the system upon repeated photocycling. Although molecular confinement is known to help stabilize reactive species, this effect is not typically employed to protect reactive intermediates and thus improve reaction yields. We envisage that performing reactions under confinement will not only improve the cyclic performance of photochromic molecules, but may also increase the amount of product obtainable from traditionally low-yielding organic reactions.

Controlling spectral and physicochemical properties with external stimuli is vital for the development of smart materials. Here we demonstrate a supramolecular gelator based on a fluorescent oxotriphenylhexanoate (OTHO) that can switch emission profiles between the solution and gel phase. Furthermore, a cocktail of the gelator and a photochromic diarylethene derivative enables four distinct emissive states to be obtained, which are modulated with light and heat as orthogonal input triggers.

Three visible-light responsive photoswitches are reported, azobis(1-methyl-benzimidazole) (1), azobis(benzoxazole) (2) and azobis(benzothiazole) (3). Photostationary distributions are obtained upon irradiation with visible light comprising approximately 80 % of the thermally unstable isomer, with thermal half-lives up to 8 min and are mostly invariant to solvent. On protonation, compound 1H+ has absorption extending beyond 600 nm, allowing switching with yellow light, and a thermal half-life just under 5 minutes. The two isomers have significantly different pKa values, offering potential as a pH switch. The absorption spectra of 2 and 3 are insensitive to acid, although changes in the thermal half-life of 3 indicate more basic intermediates that significantly influence the thermal barrier to isomerization. These findings are supported by high-level ab initio calculations, which validate that protonation occurs on the ring nitrogen and that the Z isomer is more basic in all cases.

The responses of DNA origami conformation to UV radiation of different wavelengths and doses are investigated. Short- and medium-wavelength UV light can cause photo-lesions in DNA origami. At moderate doses, the lesions do not cause any visible defects in the origami, nor do they significantly affect the hybridization capability. Instead, they help relieve the internal stress in the origami structure and restore it to the designed conformation. At high doses, staple dissociation increases which causes structural disintegration. Long-wavelength UV does not show any effect on origami conformation by itself. We show that this UV range can be used in conjunction with photoactive molecules for photo-reconfiguration, while avoiding any damage to the DNA structures.

Photochromic [Pd2L4] coordination cages based on dithienylethene (DTE) ligands L allow triggering guest uptake and release by irradiation with light of different wavelengths. The process involves four consecutive electrocyclic reactions to convert all chromophores between their open and closed photoisomeric forms. So far, guest affinity of the fully switched species was elucidated, but mechanistic details concerning the intermediate steps remained elusive. Now, a new member of the DTE cage family allows unprecedented insight into the interplay between photoisomerization steps and guest location inside/outside the cavity. Therefore, the intrinsic chirality of the DTE backbones was used as reporter for monitoring the fate of a chiral guest. In its "open" photoisomeric form ( o-L, [Pd2( o-L)4] = o-C), the C2-symmetric DTE chromophore quickly converts between energetically degenerate P and M helical conformations. After binding homochiral 1 R-( -) or 1 S-( +) camphor sulfonate ( R-CSA or S-CSA), guest-to-host chirality transfer was observed via a circular dichroism (CD) signal for the cage-centered absorption. Irradiating the R/S-CSA@ o-C host-guest complexes at 313 nm produced configurationally stable "closed" photoisomers, thus locking the induced chirality with an enantiomeric excess close to 25%. This value (corresponding to chiral induction for one out of four ligands), together with DOSY NMR, ion mobility mass spectrometry, and X-ray structure results, shows that closure of the first photoswitch is sufficient to expel the guest from the cavity.

DNA binding modes of the stereoisomeric rotamers of two dithenylethene derivatives (DTE1 and DTE2) representing candidate molecular photoswitches of great promise for photopharmacology and nanotechnology have been identified and characterized in terms of their binding energies and electronic circular dichroism (CD) responses. In the open form, two binding modes are identified namely minor-groove binding of the lowest-energy conformer with an anti-parallel arrangement of methyl groups and major-groove double-intercalation of the P-enantiomers of an intermediate-state rotamer. Only the latter binding mode is found to be enantiomerically selective and expected to have an overall negative linear dichroism (LD) as observed in the experiment for DTE1 (Angew. Chem., Int. Ed., 2013, 52, 4393). In the closed form, the most favorable binding mode is found to be minor groove binding. Also this binding mode is found to be enantiomerically selective and for DTE1, it is the M-enantiomer that binds the strongest, showing a positive theoretical signature CD band in the long wavelength region with origin in pyridinium ligands. The theoretical CD spectrum is found to be in good agreement with the experimental one, which provides an indirect evidence for a correct identification of the binding mode in the closed form.

Photochromic molecules from the spiropyran family are known to undergo light-induced interconversion between the colorless spiro- and the colored merocyanine forms. Here, we show for the first time that small structural modifications open up for an additional photoisomerization mode: reversiblecis–transisomerization of the merocyanine. Moreover, the introduction of a photocage allows for light-activated switching between the two modes.

A set of azoheteroarenes have been synthesized with Buchwald-Hartwig coupling and microwave-assisted O2 oxidation as the key steps. Several compounds exhibit good to excellent photoswitching properties (high switching efficiency, good fatigue resistance, and thermal stability of Z-isomer) relevant for photocontrolled applications, which pave the way for use in photopharmacology.

The photo-controlled shift of pH titration curves, describing the acidochromic behaviour of a spiropyran switch network, was harnessed for the realisation of a molecular triode. The intricate network can be correctly interpreted with respect to the pH dependence of the main involved species.

Two amidine-substituted spiropyran derivatives have been characterized with respect to the DNA-binding properties over a broad pH interval. The two derivatives differ in the number of positive charges. By varying the pH, the protonation state of the derivatives is also changed, allowing for additional variations in the charge distribution. We show that the closed spiro isomer does not bind for either of the two derivatives, whereas the open merocyanine forms bind both in the protonated and in the nonprotonated state, but with dramatically different binding constants. Flow-oriented linear dichroism (LD) measurements also show that there are differences in the binding modes between the various forms. We rationalize these differences in terms of structure and charge distribution.

Six water-soluble spiropyran derivatives have been characterized with respect to the thermal and photoinduced reactions over a broad pH-interval. A comprehensive kinetic model was formulated including the spiro- and the merocyanine isomers, the respective protonated forms, and the hydrolysis products. The experimental studies on the hydrolysis reaction mechanism were supplemented by calculations using quantum mechanical (QM) models employing density functional theory. The results show that (1) the substitution pattern dramatically influences the pKa-values of the protonated forms as well as the rates of the thermal isomerization reactions, (2) water is the nucleophile in the hydrolysis reaction around neutral pH, (3) the phenolate oxygen of the merocyanine form plays a key role in the hydrolysis reaction. Hence, the nonprotonated merocyanine isomer is susceptible to hydrolysis, whereas the corresponding protonated form is stable toward hydrolytic degradation.

Herein, we report the first example of one-time password (OTP) generation and two-factor authentication (2FA) using a molecular approach. OTPs are passwords that are valid for one entry only. For the next login session, a new, different password is generated. This brings the advantage that any undesired recording of a password will not risk the security of the authentication process. Our molecular realization of the OTP generator is based on a photochromic molecular triad where the optical input required to set the triad to the fluorescent form differs depending on the initial isomeric state.

A self-assembled supramolecular platform has been designed for reversibly controlling the concentration of a compound in solution, via a photochemical reaction. The system utilizes metal-ligand interactions between a Zn-porphyrin dimer and a pyridine-appended dithienylethene (DTE) photoswitch. In addition to reversible compound release, the spectral properties of the release scaffold provide a fluorescence-based reporting function. This journal is

DNA origami has received enormous attention for its ability to program complex nanostructures with a few nanometer precision. Dynamic origami structures that change conformation in response to environmental cues or external signals hold great promises in sensing and actuation at the nanoscale. The reconfiguration mechanism of existing dynamic origami structures is mostly limited to single-stranded hinges and relies almost exclusively on DNA hybridization or strand displacement. Here, we show an alternative approach by demonstrating on-demand conformation changes with DNA-binding molecules, which intercalate between base pairs and unwind DNA double helices. The unwinding effect modulates the helicity mismatch in DNA origami, which significantly influences the internal stress and the global conformation of the origami structure. We demonstrate the switching of a polymerized origami nanoribbon between different twisting states and a well-constrained torsional deformation in a monomeric origami shaft. The structural transformation is shown to be reversible, and binding isotherms confirm the reconfiguration mechanism. This approach provides a rapid and reversible means to change DNA origami conformation, which can be used for dynamic and progressive control at the nanoscale.

Information processing at the molecular level is coming of age. Since the first molecular AND gate was proposed about 20 years ago, the molecular interpretation of binary logic has become vastly more sophisticated and complex. However, the field is also at a crossroads. While cleverly designed molecular building blocks are abundant, difficult questions remain. How can molecular components be flexibly assembled into larger circuits, and how can these components communicate with one another. The concept of all-photonic switching with photochromic supermolecules has shown some interesting potential and is discussed in this review. Although the field of molecular logic was originally discussed mainly in terms of a technology that might compete with solid-state computers, potential applications have expanded to include clever molecular systems and materials for drug delivery, sensing, probing, encoding, and diagnostics. These upcoming trends, which are herein illustrated by selected examples, deserve general attention.

Photochromes are chromophores that are reversibly isomerized between two metastable forms using light, or light and heat. When photochromes are covalently linked to other chromophores, they can act as molecular photonic analogues of electronic transistors. As bistable switches, they can be incorporated into the design of molecules capable of binary arithmetic and both combinatorial and sequential digital logic operations. Small ensembles of such molecules can perform analogue signal modulation similar to that carried out by transistor amplifiers. Examples of molecules that perform multiple logic functions, act as control elements for fluorescent reporters, and mimic natural photoregulatory functions are presented.

The photochromic fluorescence switching of a fulgimide derivative was used to implement the first molecule-based D (delay) flip-flop device, which works based on the principles of sequential logic. The device operates exclusively with photonic signals and can be conveniently switched in repeated cycles. © 2011 American Chemical Society.

A molecular dyad consisting of a photochromic dihydroindolizine unit covalently linked to a porphyrin performs, when illuminated through a third-harmonic-generating crystal, the functions of both an AND and a NAND Boolean logic gate with shared all-optical inputs. The NAND gate is of particular interest as it is a so-called universal gate, and hence all other digital systems can be implemented by combinations of NAND gates. The functions of the AND and the NAND gates rely on changes in absorption and emission of the dyad in the visible spectral region upon isomerization of the photochromic unit. The change in absorption which forms the basis for the AND gate function is ascribed to the colorization/decolorization of the photochrome itself in response to the optical inputs. The variation in emission intensity which constitutes the NAND gate function is a result of the changes in redox properties of the photochrome that follow upon isomerization, such that only one of the two isomers is competent to quench the porphyrin emission by electron transfer.

A trichromophoric molecule consisting of a porphyrin linked to both a dihydropyrene and a dihydroindolizine-type photochrome, in combination with a third harmonic generating crystal, functions as a 1:2 digital demultiplexer with photonic inputs and outputs. Each of the two photochromes may be cycled independently between two metastable forms, leading to four photoisomers, three of which are used in the demultiplexer. These isomers interact photochemically with the porphyrin in order to yield the demultiplexer function. With the address input (1064-nm light) turned off, one output of the device (porphyrin fluorescence) tracks the state of the data input (532-nm light). When the address input is turned on, the second output (absorbance at 572 nm) tracks the state of the data input, while the first output remains off. The demultiplexer does not require chemical or electrical inputs, and can cycle through its operational sequences multiple times.

Proto-oncogene tyrosine-protein kinase receptor RET is implicated in the development and maintenance of neurons of the central and peripheral nervous systems. Attaching activity-compromising photocleavable groups (caging) to inhibitors could allow for external spatiotemporally controlled inhibition using light, potentially providing novel information on how these kinase receptors are involved in cellular processes. Here, caged RET inhibitors were obtained from 3-substituted pyrazolopyrimidine-based compounds by attaching photolabile groups to the exocyclic amino function. The most promising compound displayed excellent inhibitory effect in cell-free, as well as live-cell assays upon decaging. Furthermore, inhibition could be efficiently activated with light in vivo in zebrafish embryos and was shown to effect motoneuron development.

REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase required for normal development and maintenance of neurons of the central and peripheral nervous systems. Deregulation of RET and hyperactivity of the RET kinase is intimately connected to several types of human cancers, most notably thyroid cancers, making it an attractive therapeutic target for small-molecule kinase inhibitors. Novel approaches, allowing external control of the activity of RET, would be key additions to the signal transduction toolbox. In this work, photoswitchable RET kinase inhibitors based on azo-functionalized pyrazolopyrimidines were developed, enabling photonic control of RET activity. The most promising compound displays excellent switching properties and stability with good inhibitory effect towards RET in cell-free as well as live-cell assays and a significant difference in inhibitory activity between its two photoisomeric forms. As the first reported photoswitchable small-molecule kinase inhibitor, we consider the herein presented effector to be a significant step forward in the development of tools for kinase signal transduction studies with spatiotemporal control over inhibitor concentration in situ.

Small molecule nonpeptidic mimics of α-helices are widely recognised as protein-protein interaction (PPIs) inhibitors. Protein-protein interactions mediate virtually all important regulatory pathways in a cell, and the ability to control and modulate PPIs is therefore of great significance to basic biology, where controlled disruption of protein networks is key to understanding network connectivity and function. We have designed and synthesised two series of 2,6,9-substituted 8-triazolylpurines as α-helix mimetics. The first series was designed based on low energy conformations but did not display any biological activity in a biochemical fluorescence polarisation assay targeting MDM2/p53. Although solution NMR conformation studies demonstrated that such molecules could mimic the topography of an α-helix, docking studies indicated that the same compounds were not optimal as inhibitors for the MDM2/p53 interaction. A new series of 8-triazolylpurines was designed based on a combination of docking studies and analysis of recently published inhibitors. The best compound displayed low micromolar inhibitory activity towards MDM2/p53 in a biochemical fluorescence polarisation assay. In order to evaluate the applicability of these compounds as biologically active and intrinsically fluorescent probes, their absorption/emission properties were measured. The compounds display fluorescent properties with quantum yields up to 50%.

A molecular triad consisting of a porphyrin (P) covalently linked to two photochromes-one from the dihydroindolizine family (DHI) and one from the dihydropyrene family (DHP)-has been synthesized and found to act as either a molecular AND logic gate or an INHIBIT gate, depending on the inputs and initial state of the photochromes. The basis of these functions is quenching of porphyrin fluorescence (output of the gates) by the photochromes. The spiro form of DHI does not quench porphyrin fluorescence, whereas its betaine isomer strongly quenches by photoinduced electron transfer. DHP also quenches porphyrin fluorescence, but its cyclophanediene isomer does not. The triad has been designed using suitable energetics and electronic interactions, so that although these quenching phenomena may be observed, independent isomerization of the attached photochromes still occurs. This makes it possible to switch porphyrin fluorescence on or off by isomerization of the photochromes using various combinations of inputs such as UV light, red light, and heat.

We have studied the electronic changes caused by light-induced isomerization of a photochromic molecule between an open state (that absorbs in the UV to become closed) and a closed state (that absorbs in the visible to become open). Data obtained using a newly developed repetitive break junction method are interpreted in terms of single-molecule resistances of 526 +/- 90 M Omega in the open form and 4 +/- 1 M Omega in the closed form when the molecule is bound between two gold contacts via dithiol linkages. The corresponding ratio of open to closed resistance is in close agreement with the results of ab initio calculations, though the measured resistances are about half of the calculated values. Optical spectroscopy indicates that the photoisomerization occurs in both directions on small gold particles, evaporated thin gold films, and in the break junction experiments.

Gold porphyrins are often used as electron-accepting chromophores in donor-acceptor complexes for the study of photoinduced electron transfer, and they can also be involved in triplet-triplet energy-transfer interactions with other chromophores. Since the lowest excited singlet state is very short-lived (240 fs), the triplet state is usually the starting point for the transfer reactions, and it is therefore crucial to understand its photophysics. The triplet state of various gold porphyrins has been reported to have a lifetime of around 1.5 ns at room temperature and to have a biexponential decay both in emission and in transient absorption with decay times of around 10 and 100 micros at 80 K. In this paper, the triplet photophysics of two gold porphyrins (Au(III) 5,15-bis(3,5-di-tert-butylphenyl)-2,8,12,18-tetraethyl-3,7,13,17-tetramethylporphyrin and Au(III) 5,10,15,20-tetra(3,5-di-tert-butylphenyl)porphyrin) are studied by steady-state and time-resolved absorption and emission spectroscopy over a wide temperature range (4-300 K). The study reveals the existence of a dark state with an approximate lifetime of 50 ns, which was not previously observed. This state acts as an intermediate between the short-lived singlet and the triplet state manifold. In addition, we present DFT calculations, in which the core electrons of the central metal were replaced by a pseudopotential to account for the relativistic effects, which suggest that the lowest excited singlet state is an optically forbidden ligand-to-metal charge-transfer (LMCT) state. This LMCT state is an obvious candidate for the experimentally observed dark state, and it is shown to dictate the photophysical properties of gold porphyrins by acting as a gate for triplet state formation versus direct return to the ground state.

The triplet excited-state deactivation of a gold porphyrin (AuP) in porphyrin-based donor−bridge−acceptor (D−B−A) systems has been studied. The results from room temperature and 80 K measurements are presented. The primary objectives have been to investigate whether electrons/electron holes or excitation energy could be transferred from 3AuP to the appended zinc porphyrin (ZnP) in the dimers. As the bridging chromophores in our D−B−A systems separate the ZnP and AuP moieties by 19 A edge-to-edge, we do not expect a significant contribution to either electron or energy transfer from a direct (through space) exchange mechanism. This gives us the opportunity to scrutinize how the bridging chromophores influence the transfer reactions. The results show that quenching of 3AuP occurs with high efficiency in the dimers that are connected by fully conjugated bridging chromophores, whereas no quenching is observed when the conjugation of the bridge is broken. We also observed that the decay of 3AuP is complex at t...