Photoregulation of α‐Chymotrypsin Activity by Spiropyran‐Based Inhibitors in Solution and Attached to an Optical Fiber

Here the synthesis and characterization of a new class of spiropyran‐based protease inhibitor is reported that can be reversibly photoswitched between an active spiropyran (SP) isomer and a less active merocyanine (MC) isomer upon irradiation with UV and visible light, respectively, both in solution and on a surface of a microstructured optical fiber (MOF). The most potent inhibitor in the series ( SP ‐ 3 b ) has a C‐terminal phenylalanyl‐based α‐ketoester group and inhibits α‐chymotrypsin with a K_i of 115 nM . An analogue containing a C‐terminal Weinreb amide ( SP‐2 d ) demonstrated excellent stability and photoswitching in solution and was attached to the surface of a MOF. The SP isomer of Weinreb amide 2 d is a competitive reversible inhibitor in solution and also on fiber, while the corresponding MC isomer was significantly less active in both media. The ability of this new class of spiropyran‐based protease inhibitor to modulate enzyme activity on a MOF paves the way for sensing applications.     

Spiropyran Main‐Chain Conjugated Polymers

The first main‐chain conjugated copolymers based on alternating spiropyran (SP) and 9,9‐dioctylfluorene (F8) units synthesized via Suzuki polycondensation (SPC) are presented. The reaction conditions of SPC are optimized to obtain materials of type P(para‐SP‐F8) with appreciably high molecular weights up to M _w ≈ 100 kg mol⁻¹. ¹³C NMR is used to identify the random orientation of the non‐symmetric SP unit in P(p‐SP‐F8). Ultrasound‐induced isomerization of P(p‐SP‐F8) to the corresponding merocyanine form P(p‐MC‐F8) yields a deep‐red solution. This isomerization reaction is followed by ¹H NMR in solution using sonication, whereby the color increasingly changes to deep red. The possibility to incorporate multiple SP units into main‐chain polymers significantly broadens existing SP‐based polymeric architectures.     

Sensitivity and Resolution Development of Spiropyran‐based Molecular Photoswitches

The phenylazo moiety and its donor‐ and acceptor‐substituted derivatives are studied as effective auxochromes to improve their sensitivity and resolution for distinguishing between the spiro (SP; OFF) and mero (ON) forms in molecular photoswitching applications. Thus, 13 azospiropyran derivatives were synthesized and their spectroscopic and photokinetic behaviors were studied. The quality of photochromic reactions of the synthesized photochromic compounds were compared using a dose–response model. Interestingly, by replacing the nitro group in 6‐nitrospiropyran (ε = 0.42 × 10⁴ M^?1 cm^?1) with a simple phenylazo moiety, the SP form is still colorless and the color intensity of the merocyanine (MC) form is improved desirably by extending the conjugation length ( 1a , ε = 1.35 × 10⁴ M^?1 cm^?1). The presence of a hydrophilic OH group or a CH₃ group at the para position of phenylazo moiety revealed more or less the same photochromic properties as 1a . The OCH₃ group substituted at position 6 of the phenylazo moiety at the para position of the azobenzene moiety effectively increased the photochromic properties with the maximum k‐value for SP to MC switching. Meanwhile, Cl, Br, COOH, and NO₂ groups at the para position of the azobenzene moiety revealed the reduction in photochromic properties compared to 1a .     

Reversibly light‐responsive biodegradable poly(carbonate) micelles constructed via CuAAC reaction

Light‐responsive poly(carbonate)s PEG₁₁₃‐b‐PMPC_n‐SP were synthesized via copper catalyzed azide‐alkyne cycloaddition reaction between azide‐modified spiropyran (SP‐N₃) and amphiphilic copolymer PEG₁₁₃‐b‐PMPC_n. PEG₁₁₃‐b‐PMPC₂₅‐SP can self‐assemble to biocompatible micelles with an average diameter of ～96 nm and a critical aggregation concentration of 0.0148 mg mL^?1. Under 365 nm UV light irradiation, the characteristic absorption intensity of merocyanine (MC) progressively increased and most of the micellar aggregations were disrupted within 10 min, suggesting the completion of the transformation of hydrophobic SP to hydrophilic MC. Subsequent exposuring the micelles to 620 nm visible light, spherical micelles aggregated again. The light‐controlled release and re‐encapsulation behaviors of coumarin 102‐loaded micelles were further investigated by fluorescence spectroscopy. This study provides a convenient way to construct smart poly(carbonate)s nanocarriers for controlled release and re‐encapsulation of hydrophobic drugs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 750–760     

A High Contrast Tri‐state Fluorescent Switch: Properties and Applications

A high contrast tri‐state fluorescent switch (FSPTPE) with both emission color change and on/off switching is achieved in a single molecular system by fusing the aggregation‐induced emissive tetraphenylethene (TPE) with a molecular switch of spiropyran (SP). In contrast to most of the reported solid‐state fluorescent switches, FSPTPE only exists in the amorphous phase in the ring‐closed form owing to its highly asymmetric molecular geometry and weak intermolecular interactions, which leads to its grinding‐inert stable cyan emission in the solid state. Such an amorphous phase facilitates the fast response of FSPTPE to acidic gases and induces the structural transition from the ring‐closed form to ring‐open form, accompanied with the “Off” state of the fluorescence. The structural transition leads to a planar molecular conformation and high dipole moment, which further results in strong intermolecular interactions and good crystallinity, so when the acid is added together with a solvent, both the ring‐opening reaction and re‐crystallization can be triggered to result in an orange emissive state. The reversible control between any two of the three states (cyan/orange/dark) can be achieved with acid/base or mechanical force/solvent treatment. Because of the stable initial state and high color contrast (Δλ=120 nm for cyan/orange switch, dark state Φ_F<0.01 %), the fluorescent switch is very promising for applications such as displays, chemical or mechanical sensing, and anti‐counterfeiting.     

Diarylethene Self‐Assembled Monolayers: Cocrystallization and Mixing‐Induced Cooperativity Highlighted by Scanning Tunneling Microscopy at the Liquid/Solid Interface

Stimulus control over 2D multicomponent molecular ordering on surfaces is a key technique for realizing advanced materials with stimuli‐responsive surface properties. The formation of 2D molecular ordering along with photoisomerization was monitored by scanning tunneling microscopy at the octanoic acid/highly oriented pyrolytic graphite interface for a synthesized amide‐containing diarylethene, which underwent photoisomerization between the open‐ and closed‐ring isomers and also a side‐reaction to give the annulated isomer. The nucleation (K_n) and elongation (K_e) equilibrium constants were determined by analysis of the concentration dependence of the surface coverage by using a cooperative model at the liquid/solid interface. It was found that the annulated isomer has a very large equilibrium constant, which explains the predominantly observed ordering of the annulated isomer. It was also found that the presence of the closed‐ring isomer induces cooperativity into the formation of molecular ordering composed of the open‐ring isomer. A quantitative analysis of the formation of ordering by using the cooperative model has provided a new view of the formation of 2D multicomponent molecular ordering.     

Ring opening of pyridines: the pseudo‐cis and pseudo‐trans isomers of tetra‐n‐butylammonium 4‐nitro‐5‐oxo‐2‐pentenenitrilate

The reaction of 2‐chloro‐5‐nitropyridine with two equivalents of base produces the title carbanion as an intermediate in a ring‐opening/ring‐closing reaction. The crystal structures of the tetra‐n‐butylammonium salts of the intermediates, C₁₆H₃₆N⁺·C₅H₃N₂O₃⁻, revealed that pseudo‐cis and pseudo‐trans isomers are possible. One crystal structure displayed a mixture of the two isomers with approximately 90% pseudo‐cis geometry and confirms the structure predicted by the S_N(ANRORC) mechanism. The pseudo‐cis intermediate undergoes a slow isomerization over a period of months to the pseudo‐trans isomer, which does not have the appropriate geometry for the subsequent ring‐closing reaction. The structure of the pure pseudo‐trans isomer is also reported. In both isomers, the negative charge is highly delocalized, but relatively small differences in C—C bond distances indicate a system of conjugated double bonds with the nitro group bearing the negative charge. The packing of the two unit cells is very similar and largely determined by the interactions between the planar carbanion and the bulky tetrahedral cation.     

Cis‐ and trans‐bis(2‐cyano­ethyl­sulfan­yl)(decane‐1,10‐diyldithio)tetra­thia­fulvalene

The isomeric title compounds, 2,7‐bis(2‐cyanoethylsulfanyl)‐3,6‐(decane‐1,10‐diyldithio)tetrathiafulvalene and 2,6‐bis­(2‐cyanoethylsulfanyl)‐3,7‐(decane‐1,10‐diyldithio)­tetra­thiafulvalene, both C₂₂H₂₈N₂S₈, comprise bis­(2‐cyano­ethyl­sulfan­yl)tetra­thia­fulvalene units tethered by a saturated deca­methyl­enedithio linker attached in either a cis or a trans manner. The tetra­thia­fulvalene (TTF) group is planar in the cis isomer, but distorted significantly from planarity and twisted about its long axis in the trans isomer. In both structures, inter­molecular inter­actions are segregated into regions in which TTF units are brought into close contact and regions where the polymethyl­ene chains are brought into close contact. In the cis isomer, TTF units exhibit π–π stacking inter­actions, while in the trans isomer they do not.     

Stabilization of merocyanine by protonation, charge, and external electric fields and effects on the isomerization of spiropyran: a computational study

Protonation, charging, and field effects on the thermal isomerization of a nitrospiropyran (SP) modified by a thiolated etheroxide chain into merocyanine (MC) are computationally studied at the DFT level. The ring opening leads to cis-MC conformers that then isomerize to the more stable trans forms. While the closed neutral spiropyran is more stable than the conjugated open forms, the merocyanine conformers are significantly stabilized by protonation, electron attachment, and ionization. For protonation on the pyran oxygen atom and electron attachment, the MC conformers are more stable than SP, and unlike for the neutral species, the ring opening is spontaneous at room temperature. Moreover, for the pyran oxygen-protonated form, the ring opening to the cis-merocyanine becomes barrierless. On the other hand, barriers comparable to the neutral remain along the thermal pathway to the cis-merocyanine conformer for ionization or electron attachment, and the barrier for isomerization is significantly higher for the N-protonated SP form. External field effects on the neutral reaction path show that ring opening to the cis-merocyanine is favored when the field reduces the electron density on the pyran part, as also induced by the local field due to O protonation.     

(M)‐ and (P)‐8‐[(1S,2R)‐2‐hydroxy‐1‐methyl‐2‐phenylethyl]‐8‐methyl‐8,9‐dihydro‐7H‐dinaphth[2,1‐c:1′,2′‐e]azepinium bromide solvates

The title compounds are diastereoisomers with antipodean axial chirality. The M isomer crystallizes as a (1/3) acetone solvate, C₃₂H₃₀NO⁺·Br^?·3C₃H₆O, while the P isomer crystallizes as a (1/1) di­chloro­methane solvate, C₃₂H₃₀NO⁺·Br^?·CH₂Cl₂. In each structure, O—H?Br hydrogen bonds link the cations and anions to give ion pairs. The seven‐membered azepinium ring adopts the usual twisted‐boat conformation and its ring strain causes a slight curvature of the plane of each naphthyl ring.     

The keto→enol photoisomerization of N‐salicilydenemethylfurylamine: Nonadiabatic ab initio dynamics simulation

The photoinduced isomerization of cis‐keto and trans‐keto isomers in N‐salicilydenemethylfurylamine has been studied using the surface‐hopping approach at the CASSCF level of theory. After the cis‐keto or trans‐keto isomer is excited to S₁ state, the molecule initially moves to a excited‐state local minimum. The torsional motion around relative bonds in the chain drives the molecule to approach a keto‐form conical intersection and then nonadiabatic transition occurs. According to our full‐dimensional dynamics simulations, the trans‐keto and enol photoproducts are responsible for the photochromic effect of cis‐keto isomer excited to S₁ state, while no enol isomer was obtained in the photoisomerization of trans keto on excitation. The cis keto to enol and cis keto to trans keto isomerizations are reversible photochemical reactions. It is confirmed that this aromatic Schiff base is a potential molecular switch. Furthermore, the torsion of C N bond occurs in the radiationless decay of trans‐keto isomer, while it is completely suppressed by an intramolecular hydrogen bonding interaction in the dynamics of cis‐keto form. Moreover, the excited‐state lifetime of cis keto is longer than that of trans‐keto form due to the O···H N hydrogen bond.     

3‐Acetoxy­cyclo­hex‐4‐ene‐1,2‐di­carboxyl­ic anhydride

The title compound, C₁₀H₁₀O₅, was found to exist as the endo–cis isomer with a pair of enantiomers in the asymmetric unit. The cyclo­hexene ring is folded about the methyl­ene‐to‐CH(acetoxy) vector to give a boat conformation.     

Theoretical investigation on the spectroscopic properties of furylfulgide with different substituents and design of novel bis‐furylfulgimide photochromes

Density functional theory and time‐dependent density functional theory were employed to theoretically analyze the effect of different substituents on the spectroscopic properties of furylfulgide. The result shows that the absorption spectra of ring‐closed isomer which substituted by an electron‐donating group (NH₂) at the R₃‐position of furylfulgide has an evident bathochromic shift compared with the others. Due to the steric hindrance effect, the difference of absorption wavelength was evidently enlarged by introducing several representative electron‐withdrawing groups at the R₆‐position of furylfulgide. In addition, we also designed a series of novel dimers which combined two furylfulgimide monomers into one new molecule. The relevant frontier molecular orbitals, energy levels and absorption properties were analyzed in detail by the calculation of low‐lying excited states. Finally, taking BFF‐6 (bis‐furylfulgimide) for an example, we discussed the transformation mechanism of four stable isomers in the toluene solution. Our conclusions manifest that the asymmetrical BFF‐6 can act as a potential multifunctional molecular switch in consideration of its distinguishable absorption bands and reversible conversion process. We hope that this research will be beneficial to design more practical and efficient molecular switch for further applications.     

An unusual acid: (±)‐3‐benzoyl‐1,2‐dimethyl‐8a‐phenyl‐2‐benzo­thieno­[2,3‐b]pyrrole‐1,2‐dicarboxylic anhydride

The title compound, C₂₇H₂₁NO₄S, is a 2‐benzothieno[2,3‐b]pyrrole derivative with several substituents, present in the crystal as a racemate. The tetra­cyclic fused‐ring system shows a `U‐shaped' mol­ecular architecture, since the two rings flanking the central pyrrolidine ring both point in the same direction.     

rac‐9‐Ethyl‐12a‐hydroxytetradecahydrotriphenylene‐1,5(2H,4bH)‐dione: stabilization of a new isomer of a functionalized perhydrotriphenylene through a tandem Michael addition–aldol reaction

The title compound, C₂₀H₃₀O₃, is a new functionalized perhydrotriphenylene derivative formed via a tandem Michael addition–aldol reaction. The structural study reveals that the system of fused rings approximates a C₂ point symmetry, with trans–cis–cis ring junctions, while highly symmetric all‐trans perhydrotriphenylene, previously characterized, approximates a D₃ symmetry. The perhydrotriphenylene nucleus of the title compound corresponds to the third stable stereoisomer isolated for this polycyclic system. Considering that the C_s isomer was obtained recently through a similar tandem reaction, a general strategy is proposed which may help to obtain other stable stereoisomers of perhydrotriphenylene.     

tert‐Butyl (6S)‐4‐hydroxy‐6‐isobutyl‐2‐oxo‐1,2,5,6‐tetra­hydropyridine‐1‐carboxyl­ate and tert‐butyl (4R,6S)‐4‐hydroxy‐6‐iso­butyl‐2‐oxopiperidine‐1‐carboxyl­ate

X‐ray studies reveal that tert‐butyl (6S)‐6‐iso­butyl‐2,4‐dioxo­piperidine‐1‐carboxyl­ate occurs in the 4‐enol form, viz. tert‐butyl (6S)‐4‐hydroxy‐6‐iso­butyl‐2‐oxo‐1,2,5,6‐tetra­hydropyri­dine‐1‐carboxyl­ate, C₁₄H₂₃NO₄, when crystals are grown from a mixture of di­chloro­methane and pentane, and has an axial orientation of the iso­butyl side chain at the 6‐position of the piperidine ring. Reduction of the keto functionality leads predominantly to the corresponding β‐hydroxy­lated δ‐lactam, tert‐butyl (4R,6S)‐4‐hydroxy‐6‐iso­butyl‐2‐oxo­piperidine‐1‐car­boxyl­ate, C₁₄H₂₅NO₄, with a cis configuration of the 4‐hydroxy and 6‐iso­butyl groups. The two compounds show similar molecular packing driven by strong O—H⋯O=C hydrogen bonds, leading to infinite chains in the crystal structure.     

1,2‐Dithienyldicyanoethene‐Based,Visible‐Light‐Driven,Chiral Fluorescent Molecular Switch: Rewritable Multimodal Photonic Devices

Reported here is the first example of a 1,2‐dithienyldicyanoethene‐based visible‐light‐driven chiral fluorescent molecular switch that exhibits reversible trans to cis photoisomerization. The trans form in solution almost completely transforms into the cis form, accompanied by a 10‐fold decrease in its fluorescence intensity within 60 seconds when exposed to green light (520 nm). The reverse isomerization proceeds upon irradiation with blue light (405 nm). When doped into commercially available achiral liquid crystal hosts, this molecular switch efficiently induces luminescent helical superstructures, that is, a cholesteric phase. The intensity of the circularly polarized fluorescence as well as the selective reflection wavelength of the induced cholesteric phases can be reversibly tuned using visible light of two different wavelengths. Optically rewritable photonic devices using cholesteric films containing this molecular switch are described.     

A Conformational Study of Cyclohexane‐1,3,5‐tricarbonitrile Derivatives

Cyclohexane‐1,3,5‐tricarbonitrile reached equilibrium having 1,3‐cis‐1,5‐cis and 1,3‐cis‐1,5‐trans isomers in a ratio of 3:7. The cis, cis‐isomer preferred the conformation with three equatorial cyano groups, where as the cis, trans‐isomer displayed two cyano groups on equatorial positions and another cyano group on axial position. Condensation of cis, cis‐cyclohexane‐1,3,5‐tricarbonitrile with L‐(S)‐valinol by the catalysis of ZnCl₂ in refluxing 1,2‐dichlorobenzene afforded two isomeric cyclohexane‐1,3,5‐trioxazolines in favor of the 1,3‐cis‐1,5‐trans isomer. Metalation of cis, cis‐cyclohexane‐1,3,5‐tricarbonitrile, followed by alkylations with dimethyl sulfate, benzyl bromide or allyl bromide, gave the cor responding trialkylation products with predominance of 1,3‐cis‐1,5‐trans isomers. The cis, trans‐isomer showed two cyano groups on axial positions and another cyano group on equatorial position, where as the cis, cis‐isomer exhibited three axial cyano groups. Treatment of trimethyl cis, cis‐cyclohexane‐1,3,5‐tricarboxylate with lithium diisopropylamide and dimethyl sulfate afforded mainly the trimethyl ester of Kemp's triacid, which showed three axial carboxylate groups. Two competitive factors, i.e. the steric effect of in coming electrophiles and the dipole‐dipole inter actions of the cyano or carboxylate groups, might inter play to give different stereoselectivities in these reaction systems.     

1,2‐Dithienyldicyanoethene‐Based,Visible‐Light‐Driven,Chiral Fluorescent Molecular Switch: Rewritable Multimodal Photonic Devices

Reported here is the first example of a 1,2‐dithienyldicyanoethene‐based visible‐light‐driven chiral fluorescent molecular switch that exhibits reversible trans to cis photoisomerization. The trans form in solution almost completely transforms into the cis form, accompanied by a 10‐fold decrease in its fluorescence intensity within 60 seconds when exposed to green light (520 nm). The reverse isomerization proceeds upon irradiation with blue light (405 nm). When doped into commercially available achiral liquid crystal hosts, this molecular switch efficiently induces luminescent helical superstructures, that is, a cholesteric phase. The intensity of the circularly polarized fluorescence as well as the selective reflection wavelength of the induced cholesteric phases can be reversibly tuned using visible light of two different wavelengths. Optically rewritable photonic devices using cholesteric films containing this molecular switch are described.     

Fused‐ring nitrogen and sulfur heterocycles by a tandem SN2‐michael addition reaction

A tandem S_N2‐Michael addition reaction has been developed for the synthesis of cis‐ and trans‐fused nitrogen and sulfur heterocycles from the cis and trans isomers of ethyl (±)‐(2E)‐3‐[2‐(iodomethyl)cyclo‐hexyl]‐2‐propenoate. Octahydro‐1H‐isoindole‐1‐acetic acid and octahydrobenzo[c]thiophene‐1‐acetic acid derivatives have been prepared and their stereochemistries elucidated using NMR and X‐ray crystallo‐graphic methods. Cyclization substrates for both the cis‐ and the trans‐fused rings are readily available in four steps from known compounds. Yields for the cyclization range from 80‐85% and stereochemical selec‐tivities with respect to the side chain vary from 12.5‐16:1 for the cis‐fused structures to 6‐7.5:1 for the trans‐fused structures. Steric interactions in the transition states for ring closure are proposed to rationalize the observed preferences.