Ring-opened Form Research Articles

THEORETICAL INVESTIGATION ON PHOTOISOMERIZATION SWITCHABLE SECOND-ORDER NONLINEAR OPTICAL PROPERTIES OF Λ-SHAPED DIARYLETHENE DERIVATIVES

The nonlinear optical (NLO) properties of Λ-shaped diarylethene (DAE) derivatives 1a(b)–4a(b) and their NLO switching effects were studied by using the density functional theory (DFT) methods. The results demonstrate that all of the open-ring molecules and their own closed-ring forms meet the model of NLO switching tuned by photoisomerization. The βtot values of 1b–3b are 16 times as small as that of their open-ring forms, and βtot value of 4b is 4 times as large as that of 4a. The spin interactions of open-shell closed-ring molecules are larger than that of their open-ring forms, and it could increase the NLO responses to some degree. Nature bond orbital (NBO) calculations indicate that large charge differences between electron-deficient and electron-rich centers are beneficial to charge transfer (CT), and the overlap between frontier molecular orbital (FMO) is also advantageous to the CT and NLO responses. Time-dependent density functional theory (TD-DFT) calculations show βtot values of all molecules meet the two-level model very well, and the smaller the ΔE ge , the larger the βtot value.

Photo-induced reversible proton dissociation of spirobenzopyran in aqueous systems

We report detailed behavior of the spirobenzopyran covalently attached to poly(N,N-dimethylacrylamide), which exhibits reversible and drastic proton dissociation in response to blue light in aqueous system. The molar absorption coefficient spectra of the chromophores in open-/closed-ring forms and their protonated forms were isolated respectively from the data obtained in the various conditions of proton concentration and light irradiation. From the systematic analysis using these spectra, the content ratios of the four forms of the chromophores were estimated for the conditions in the dark and under irradiation at various proton concentrations, revealing the quantitative aspect of drastic proton dissociation in response to the light irradiation. The pKa values of the protonated chromophores in the open-ring form, which is dominant in the dark, and closed-ring form, which is dominant under irradiation, were estimated to be 6.8 and 2.6, respectively. Further, drastic photo-induced proton dissociation and the recovery in the dark were repeated more than 10 times without resulting critical degradation. As a direct evidence of the drastic photo-induced proton dissociation from the chromophores, significant pH drop from over 6 to below 4 was observed for the aqueous polymer solution in rapid response to light irradiation.

The molecular design, synthesis and photochromic properties of spirooxazines containing a permanent azo (hydrazone) chromophore

Abstract A range of molecular modelling techniques has been applied to predict optimized geometrical conformations and energies of the ring-closed oxazine form and ring-opened merocyanine forms of three azospirooxazines. A comparison of the relative stabilities of the possible isomers of the merocyanines was carried out by applying molecular mechanics (augmented MM2), while the prediction of the potential for photochromic behaviour was made by comparison of the heats of formation calculated by AM1. Synthetic routes were explored and as a result two azospirooxazines were isolated, one of which showed interesting and unusual photochromic behaviour. The instability of this compound towards purification by chromatography was investigated. The decomposition product was isolated and characterized with the aid of single crystal x-ray crystallography. The correlation between predicted and observed photochromic behaviour is discussed.

Synthesis and biological evaluation of novel aliphatic amido-quaternary ammonium salts for anticancer chemotherapy: Part II

A series of novel aliphatic amido-quaternary ammonium salts were synthesized and evaluated for their anticancer effects involving induction of RhoB. Most of these compounds, featuring open-ring forms of aliphatic amido-quaternary ammonium salts, exhibited potent anti-proliferative activities in human cancer cell lines, including PC-3, NUGC-3, MDA-MB-231, ACHN, HCT-15, and NCI-H23. In further evaluation, the representative compound N,N-diethyl-N-(2-(N-methyltetradecanamido)ethyl)prop-2-en-1-aminium bromide (3b) exhibited potent pro-apoptotic activity, through RhoB activation, in HeLa cells.

Theoretical studies on the photoisomerization-switchable second-order nonlinear optical responses of DTE-linked polyoxometalate derivatives

The switchable second-order nonlinear optical (NLO) responses of the photoisomerized chromophore dithienylperfluorocyclopentene (DTE) derivatives, organic–inorganic systems of Lindqvist-type [Mo6O19]2−, have been investigated by tuning open-ring and the closed-ring form. In the present paper, we performed density functional theory (DFT) combined with finite field (FF) methods to calculate the second-order NLO coefficients for these organic-inorganic compounds. The calculations with three functionals (B3LYP/CAM-B3LYP/LC-BLYP) confirm the switching behavior on NLO properties by the photoisomerization reaction. The βtot value of system 2c (closed-ring form) is 10 times larger than that of its open-ring form (system 2o). And the other two pairs of systems also show good tuning properties. The ampliative ratio on second-order NLO coefficients between systems 2o and 2c (β2c/β2o) is 13 times as large as that of DTE (βDTEc/βDTEo). It suggests that introduction of [Mo6O19]2− and organic groups to the DTE monomer effectively improve the conversion ratio of second-order NLO coefficients between the open-ring and closed-ring forms.

Construction of NIR and ratiometric fluorescent probe for Hg2+ based on a rhodamine-inspired dye platform

A rhodamine-inspired fluorescence dye (2) bearing 7-diethylaminocoumarin fluorophore was designed as a platform for the construction of an NIR and ratiometric fluorescent probe. The ring-open form of 2 shows NIR absorption and emission; however, its ring-closed form displays the visible absorption and emission because an intact 7-diethylaminocoumarin fluorophore was involved in the structure, providing the basis for an NIR and ratiometric fluorescent platform based on the spirocyclization-induced fluorescence switching mechanism. With the platform, we developed a novel NIR and ratiometric fluorescent probe R1, a thiolactone of 2, for sensing Hg2+, an environmentally and biologically concerned species. R1 displays an emission peak with the maximum at 480 nm, which is the typical emission of 7-diethylaminocoumarin moiety; however, upon addition of Hg2+ ions, the emission intensity at 480 nm gradually decreased with the simultaneous appearance of a new NIR emission band centred at 695 nm. Thus, the Hg2+-promoted ratiometric fluorescence response can be realized. The high selectivity towards Hg2+ over various cations and the high stability in a wide pH range of 1–12 indicate its potential for applications in biological systems. The subsequent cell imaging experiment revealed that R1 is cell permeable, and could be employed for ratiometric fluorescence imaging of Hg2+ in living cells.

An acid catalyzed reversible ring-opening/ring-closure reaction involving a cyano-rhodamine spirolactam

Cyanamide was introduced into the rhodamine spirolactam framework to produce a colorless and non-fluorescent compound RBCN. It shows a reversible ring-opening/ring-closure process in response to the solution pH, which exhibits an "ON/OFF" switching in its fluorescence. Different from other rhodamine-type dyes, the ring-open form of RBCN is stable in protic solvents under neutral, near neutral and basic conditions, showing a pink color and very strong fluorescence. We also demonstrated the potential of RBCN in live cell imaging.

Drifted catalytic properties of β-lactamases due to unconstrained use of antibiotics

Context: Antibiotic resistance is an old problem with new face as the rate of infections due to multidrug resistant bacteria is increasing everyday and the number of new antibiotics to overwhelm the problem is becoming smaller. Major mechanism beneath this growing resistance is concomitant with the changes in ?-lactamases catalytic activity and its functional enhancement. Objectives: In ?-lactamases secreting clinical isolates at least 10% are extended-spectrum ?-lactamases (ESBL) that are not even treatable with ?-lactamases inhibitor like clavulanic acids. This implies that the catalytic domains of ?-lactamases have been mutated towards higher pathogenicity. The aim of the present study is to define the changes in ?-lactamases catalytic efficiency against ?-lactam antibiotics and its inhibitors. Materials and Methods: In this research work we have used multiple drug resistant (MDR) strains from surgical site of infections. A rapid method was used for specific detection of bacterial ?-lactamases that uses ?-lactam antibiotics as substrates. In this, the end products (open beta-lactam ring forms) generated after separately incubating substrates with ?-lactamases producing strains. Those end products of antibiotics were highly fluorescent after specific treatment and could be analyzed visually under long-wave UV lamp for efficiency. Results: ?-lactamases secreting strains are variably capable of defending ?-lactam antibiotics. Interestingly, one of the E. coli strain secretes ESBL, this means that the strain is resistant against clavulanic acid. However, the most fascinating fact of the finding is that ideally the ?-lactamases supposed to hydrolyze Penicillin by default but in our isolates, ?-lactamases are not able to hydrolyze penicillin instead they hydrolyze amoxicillin, a derivative which replaced clinical use of penicillin. In addition to that we have identified the presence of New Delhi Metalo- beta- lactamase in one of the clinical isolates. Conclusion: Rate of evolution in microbes is very high. Thus we presume that some of the amino acids in the functional domain of ?-lactamases have been changed respective to extinct use of penicillin whereas it is effective against clinically used other beta lactam antibiotics. DOI: http://dx.doi.org/10.3329/jbs.v19i0.12999 J. bio-sci. 19 37-42, 2011

Effects of electrode orientation on the transport properties of pyridine-terminated dithienylethene light molecule switch under bias

Prior to this work, the effects of the electrode orientation and the bias voltage on the pyridine-terminated dithienylethene molecules have not been investigated, although the switching effect of the molecules have been reported experimentally. Using the first-principles density-functional theory and nonequilibrium green’s function formalism, the present study examined the switching behaviors of open-ring and closed-ring forms of pyridine-terminated dithienylethene molecules between different crystallographic orientations of electrodes and under different bias voltages. The characteristics of I–V curves are investigated, and the negative differential resistance behavior is observed for the open-ring forms with different electrodes.

A Comprehensive Strategy to Discover Inhibitors of the Translesion Synthesis DNA Polymerase κ

Human DNA polymerase kappa (pol κ) is a translesion synthesis (TLS) polymerase that catalyzes TLS past various minor groove lesions including N 2-dG linked acrolein- and polycyclic aromatic hydrocarbon-derived adducts, as well as N 2-dG DNA–DNA interstrand cross-links introduced by the chemotherapeutic agent mitomycin C. It also processes ultraviolet light-induced DNA lesions. Since pol κ TLS activity can reduce the cellular toxicity of chemotherapeutic agents and since gliomas overexpress pol κ, small molecule library screens targeting pol κ were conducted to initiate the first step in the development of new adjunct cancer therapeutics. A high-throughput, fluorescence-based DNA strand displacement assay was utilized to screen ∼16,000 bioactive compounds, and the 60 top hits were validated by primer extension assays using non-damaged DNAs. Candesartan cilexetil, manoalide, and MK-886 were selected as proof-of-principle compounds and further characterized for their specificity toward pol κ by primer extension assays using DNAs containing a site-specific acrolein-derived, ring-opened reduced form of γ-HOPdG. Furthermore, candesartan cilexetil could enhance ultraviolet light-induced cytotoxicity in xeroderma pigmentosum variant cells, suggesting its inhibitory effect against intracellular pol κ. In summary, this investigation represents the first high-throughput screening designed to identify inhibitors of pol κ, with the characterization of biochemical and biologically relevant endpoints as a consequence of pol κ inhibition. These approaches lay the foundation for the future discovery of compounds that can be applied to combination chemotherapy.

Sterically Crowding the Bridge of Dithienylcyclopentenes for Enhanced Photoswitching Performance

Better switching: The introduction of bulky substituents into the bridge moiety of dithienylethenes led to derivatives exhibiting high photocyclization quantum yields. This novel and versatile form of substitution facilitated tuning of the switching performance without compromising on the optical and redox properties of the ring-open and ring-closed forms (see scheme).

Nondestructive Photoluminescence Read‐Out by Intramolecular Electron Transfer in a Perylene Bisimide‐Diarylethene Dyad

A novel, highly stable photochromic dyad 3 based on a perylene bisimide (PBI) fluorophore and a diarylethene (DAE) photochrome was synthesized and the optical and photophysical properties of this dyad were studied in detail by steady-state and time-resolved ultrafast spectroscopy. This photochromic dyad can be switched reversibly by UV-light irradiation of its ring-open form 3 o leading to the ring-closed form 3 c, and back reaction of 3 c to 3 o by irradiation with visible light. Solvent-dependent fluorescence studies revealed that the emission of ring-closed form 3 c is drastically quenched in solvents of medium (e.g., chloroform) to high (e.g., acetone) polarities, while the emission of the ring-open form 3 o is appreciably quenched only in highly polar solvents like DMF. The strong fluorescence quenching of 3 c is attributed to a photoinduced electron-transfer (PET) process from the excited PBI unit to ring-closed DAE moiety, as this process is thermodynamically highly favorable with a Gibbs free energy value of -0.34 eV in dichloromethane. The electron-transfer mechanism for the fluorescence quenching of ring-closed 3 c is substantiated by ultrafast transient measurements in dichloromethane and acetone, revealing stabilization of charge-separated states of 3 c in these solvents. Our results reported here show that the new photochromic dyad 3 has potential for nondestructive read-out in write/read/erase fluorescent memory systems.

Transport properties of graphene functionalized with molecular switches

We provide a theory of the electronic transport properties of a graphene layer functionalized with molecular switches. Our considerations are motivated by the spiropyran–merocyanine system which is non-polar in its ring-closed spiropyran form and zwitterionic in its ring-open merocyanine form. The reversible switching between these two isomers affects the carriers in graphene through the associated change in the molecular dipole moment, turning the graphene layer into a sensor of the molecular switching state. We present results for both the quasiclassical (Boltzmann) and the quantum coherent regimes of transport. Quite generally, we find a linear sensitivity of the conductance on the molecular dipole moment whenever quantum interference effects play an essential role which contrasts with a quadratic (and typically weaker) dependence when quantum interference is absent.

3-(1-Cyclohexylpyrrolidin-2-ylidene)-3H-indole and 4-(cyclohexylamino)-1-(1H-indol-3-yl)butan-1-one – the balance between enaminimine and ring-opened forms

Reaction of indole with the combination 1-cyclohexyl-2-pyrrolidinone and phosphoric trichloride gives the hydrochloride of 3-(1-cyclohexylpyrrolidin-2-ylidene)-3H-indole. Treatment of this with base at room temperature causes hydrolytic ring opening producing 4(cyclohexylamino)-1-(1 H-indol-3-yl)butan-1-one but careful low-temperature basification allows the isolation of 3-(1-cyclohexylpyrrolidin-2-ylidene)-3H-indole itself. The crystal structure of the hydrochloride, as a dihydrate, was determined.

Anidulafungin—challenges in development and validation of an LC-MS/MS bioanalytical method validated for regulated clinical studies

Anidulafungin is a semi-synthetic echinocandin with antifungal activity, usually administered as an intravenous infusion. In order to determine the pharmacokinetics (PK) of anidulafungin in pediatric patients, a sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) bioanalytical method (M1) was developed and validated for quantification of anidulafungin in plasma. During analysis of incurred samples (samples collected from patients enrolled in a clinical study) an isobaric chromatographic interference was observed. The source of interference was identified as an anidulafungin open-ring form (D1) and its impact on the quantification of anidulafungin was investigated. It was found that accurately quantifying anidulafungin in incurred samples required chromatographic separation of the open-ring form from anidulafungin. The method was redeveloped to achieve the appropriate baseline separation and to avoid experimental conditions that favored opening the anidulafungin ring. The extraction of anidulafungin from plasma by protein precipitation remained unchanged, but the changes in chromatography warranted validation of a new method, M2, 2 years after M1 was validated. Incurred samples from three studies that were previously analyzed by M1 and were within confirmed long-term frozen stability were then reanalyzed by M2. Although the incurred sample reproducibility tests on those samples passed for each of the two methods, comparison of concentrations from the same samples obtained by M1 and M2 revealed that an overestimation of anidulafungin following the M1 method exceeded acceptance criteria. The new HPLC-MS/MS method (M2) is applicable for quantification of anidulafungin within a nominal range 50-20,000 ng/mL and requires a 50 μL human plasma aliquot. A linear, 1/concentration squared weighted, least-squares regression algorithm was used to generate the calibration curve and its parameters were used to quantitate the incurred samples. The inter-assay accuracy in heparin human plasma validation ranged from -4.33 to 0.0386 % and precision was ≤7.32 %. The method M2 was validated for use in regulated bioanalysis and is presently used to quantitate anidulafungin in plasma samples from clinical studies.

3′,6′-Bis(ethylamino)-2′,7′-dimethyl-2-{2-(E)-[(thiophen-2-yl)methylideneamino]ethyl}spiro[isoindoline-1,9′-xanthen]-3-one methanol monosolvate

The title compound, C33H34N4O2S·CH3OH, was prepared as a spiro­lactam ring formation of rhodamine 6 G dye for comparison with a ring-opened form. The xanthene and spiro­lactam rings are approximately planar [r.m.s. deviations from planarity = 0.122 (3) and 0.072 (6) Å, respectively]. The dihedral angles formed by the spiro­lactam and thio­phene rings with the xanthene ring system are 89.7 (6) and 86.5 (2)°, respectively. The crystal structure features N—H⋯O and C—H⋯O hydrogen bonds.

A fluorescent sensor for pH based on rhodamine fluorophore

In this study, an ‘Off–On’-type acidic pH fluorescent chemosensor, 3′,6′-Bis (ethylamino)-2′,7′-dimethyl-2-(2-oxoethylideneamino)spiro[isoindoline-1,9′-xanthen]-3-one (RG1) has been designed, synthesized, and characterized by high-resolution mass spectrometry (HRMS), X-ray crystallography, infrared spectroscopy (IR), and 1H NMR and 13C NMR spectroscopy. The design tactics for the sensor was based on the change in structure between spirocyclic (non-fluorescent) and ring-open (fluorescent) forms of rhodamine dyes. Fluorescence “off–on” behaviors of RG1 were investigated on the basis of variable acid concentrations. The pH titrations showed a ca. 581-fold increase in fluorescence intensity within the pH range of 7.5 to 1.1 with a pKa value of 2.32 in acetonitrile–water (1:1, v/v) solution when excited at 510 nm. The fluorescence change of RG1 was fully reversible and took place mainly within the pH range from 1.0 to 4.0, which was valuable for pH researches in acidic environments.

Redox and photoisomerization switching of the second-order optical nonlinearity of a tetrathiafulvalene derivative of spiropyran across five states: a DFT study

Second-order nonlinear optical properties of a tetrathiafulvalene (TTF) derivative of spiropyran have been studied based on density functional theory (DFT) combined with the finite field (FF) calculations. Our DFT-FF calculations confirm a switching behavior of the static first hyperpolarizability caused by the redox and photochromic reaction. The photochromic reaction generates spiropyran-merocyanine conversion by reversible cleavage of the C-O bond, which is relative to the close- and open-ring forms 1-c and 1-o. The open-ring form 1-o displays the large static first hyperpolarizability relative to its close-ring form 1-c according to our DFT-FF calculations with three functionals. The electronic structure analysis and spin unrestricted calculations show that the redox processes significantly affect the geometrical structure of the TTF unit, and thus enhance the static first hyperpolarizabilities. The one-electron-oxidized species having good planar structure of the TTF unit are ~30 and ~200 times as large as that of the neutral compounds 1-c and 1-o, respectively. But the difference in the static first hyperpolarizability between one- and two-electron-oxidized states of spiropyran species is not substantial according to our DFT-FF calculations, and the spiropyran-merocyanine conversion of two-electron-oxidized species does not largely affect their static first hyperpolarizability. On the basis of the large change in the static first hyperpolarizability, our DFT-FF calculations support a five-state switching of the static first hyperpolarizability based on the redox and photoisomerization.

Mono- and ditopic models of binding of a photochromic chromene annelated with an 18-crown-6ether with protonated amino acids

In this work, the interaction of protonated amino acids with a chromene bearing a fused 18-crown-6 ether moiety was studied by UV-vis and NMR spectroscopy. Initial closed forms of the chromene form monotopic 1 : 1 complexes, the ammonium group being localized inside the crown ether cavity. UV-irradiation leads to transformation of the ring-closed species into the ring-opened form. Depending on the amino acid length, either ditopic or monotopic 1 : 1 complexes are formed. Such complexes are stabilized by the additional H-bonding between the carboxylic group of the acid and the carbonyl oxygen atom of the ring-opened form. Cessation of the irradiation results in ring-closure to the chromene with concomitant change of the complexation mode.

Photoswitching of bis-spiropyran using near-infrared excited upconverting nanoparticles

Bis-spiropryran molecules were grafted onto the surface of upconverting nanoparticles. Fluorescence resonance energy transfer from the upconverting nanoparticles to the surface bis-spiropyran molecules triggered the transformation of the ring-closed bis-spiropyran to the ring-open bis-merocyanine forms.