Parallel Conformation Research Articles

Aggregation-induced emission, multiple chromisms and self-organization of N-substituted-1,8-naphthalimides

Most aggregation-induced emission (AIE) luminogens possess propeller-like aromatic stator-rotor structures, such as silole, tetraphenylethylene (TPE) and triphenylamine (TPA), to restrict intra-molecular motions (RIM) and avoid aggregation-caused quenching (ACQ) effects. In our work, two simple N-substituted naphthalimides were designed and synthesized by the amide condensation to create novel AIE systems. Except for the same aromatic stator (naphthalimide), N-phenyl-1,8-naphthalimide (PhNI) contained an aromatic rotor (phenyl group) while N-cyclohexyl-1,8-naphthalimide (CyNI) contained an aliphatic rotor (cyclohexyl group). The PhNI samples obtained from different preparation processes showed multiple chromisms (MC) effects and varied levels of luminescence. Despite of the same intra-molecular structure, the crystal of PhNI had staggered parallel inter-molecular conformation with weak emission but the precipitation of PhNI had cross one with strong emission. Although without MC effects, CyNI gave an excellent fluorescence quantum yield (Φf = 0.55). The experimental results and theoretical analyses suggested that the AIE effects were decided by intra- and inter-molecular structure simultaneously and the construction and destruction of inter-molecular π-π stacking between aromatic rotors in PhNI resulted in the MC effects.

Real-Time Monitoring of Insulin Using a Graphene Field-Effect Transistor Aptameric Nanosensor.

This paper presents an approach to the real-time, label-free, specific, and sensitive monitoring of insulin using a graphene aptameric nanosensor. The nanosensor is configured as a field-effect transistor, whose graphene-based conducting channel is functionalized with a guanine-rich IGA3 aptamer. The negatively charged aptamer folds into a compact and stable antiparallel or parallel G-quadruplex conformation upon binding with insulin, resulting in a change in the carrier density, and hence the electrical conductance, of the graphene. The change in the electrical conductance is then measured to enable the real-time monitoring of insulin levels. Testing has shown that the nanosensor offers an estimated limit of detection down to 35 pM and is functional in Krebs-Ringer bicarbonate buffer, a standard pancreatic islet perfusion medium. These results demonstrate the potential utility of this approach in label-free monitoring of insulin and in timely prediction of accurate insulin dosage in clinical diagnostics.

Inter-Digitated Photo-Active Strands

In natural photosynthetic systems, the solar energy is collected by pigment molecules attached to the light harvesting complexes. In these units, the chlorophylls are held in a favored spacing and orientation by fairly short α-helical polypeptides.1 When a photon hits one of the chlorophylls, the absorbed energy spreads extremely rapidly to the others until the reaction center is reached within the cell membrane, where the solar energy is converted into chemical energy used by the cell to grow. In this way, the energy contained in a single photon is conducted in a very short time and with minimal loss of energy from the point where it is absorbed to where it is needed. The extraordinary efficiency of the energy migration over long distances with minimal loss of energy is ascribed to the favored spacing and orientation of the chlorophylls which are held in an appropriate parallel conformation. Beyond the control of the structure of multi-chromophoric arrays, monitoring the spatial orientation of the chromophores in artificial light harvesting devices is a challenge of growing interest. Indeed, multi-porphyrinic arrays attract more and more attention for the elaboration of photonic and electronic wires.2 An octapeptide3 and an hexadecapeptide4 derived from the L-lysine and functionalized with porphyrins have been prepared. Beyond a certain degree of oligomerisation, we observed the development of a secondary structure such as a 310 helix which forces the porphyrins to arrange in a defined spatial arrangement. Due to the overlap of the porphyrins in such a conformation, the chromophores undergo a sufficient electronic coupling to favor a good exciton migration.5 The ability of these peptides to accomodate guests was investigated through ligand binding studies carried out in dichloromethane with DABCO as bidentate base. The complexation of DABCO by these peptides was monitored by UV-visible spectrophotometric titration in CH2Cl2. We showed that the enhanced stability of the complexe octapeptide/DABCO can be ascribed to a pre-organization of the octapeptide forming cavities, and provides convincing evidence that the bidentate base is inserted into the cavities of the octapeptide via host/guest interactions. Acknowledgements This work was supported by the CNRS and the French Ministry of Research. References W. Kühlbrandt, Nature 1995, 374, 497-498. a) R. W. Wagner, J. S. Lindsey, J. Seth, V. Palaniappan, D. F. Bocian, J. Am. Chem. Soc. 1996, 118, 3996-3997 and ref. cited therein. b) M. J. Crossley, P. L. Burn, S. J. Langford, J. K Prashar, J. Chem. Soc., Chem. Commun. 1995, 1921-1923. c) A. Osuka, H. Shimidzu, Angew. Chem. Int. Ed. Engl. 1997, 36, 135-137. N. Solladié, A. Hamel, M. Gross, Tet. Lett. 2000, 41, 6075-6078. Unpublished results. a) M. Fujitsuka, M. Hara, S. Tojo, A. Okada, V. Troiani, N. Solladié, T. Majima, J. Phys. Chem B. 2005, 109, 33-35. b) M. Fujitsuka, D. W. Cho, N. Solladié, V. Troiani, H. Qiu, T. Majima, J. Photochem. Photobiol. A 2007, 188, 346-350. Figure 1

Nucleosides As Organizing Architectural Moieties

Chemistry “beyond the molecule” is epitomized in nature by a plethora of relatively weak noncovalent interactions. The three-dimensional structures of most biopolymers are controlled with noncovalent interactions, either between different parts of the same strand (as in protein α-helices) or between two separate strands (as in the DNA duplex and protein β-sheet). While nature has refined the construction of biopolymers, our mastery of the subtle noncovalent interactions as synthetic tools is in an early stage of development. Only in the past two decades people begun to develop ways of mimicking the natural light-harvesting complexes by noncovalent assembly of porphyrin units aiming to obtain favored spacing and orientation between the chromophores. The construction of multi-chromophoric assemblies has led to resurgence of interest in coordination chemistry due to formation of ordered arrays directed through molecular recognition events. As a module in the construction of supramolecular assemblies, porphyrins and metallo-porphyrins can be exploited in two different ways: porphyrins can behave as donor building blocks insofar as they comprise meso-substituents, such as pyridyl groups, which can act as ligands that can suitably coordinate to metal cations, while metalloporphyrins can act as acceptor building blocks as soon as the metal atom inside the porphyrin core has at least one axial site available for coordination. For the last years, we have focussed on cofacial bis-porphyrin tweezers for host/guest interactions and investigated the possibilty to obtain self-coordinated molecular systems with predictable spectral and redox characteristics. We report here the synthesis of a di-nucleotide bearing pendant porphyrins dedicated to adopt a pre-organized coformation with face-to-face porphyrins, and capable to self-organize in a stable sandwich type complexe with bidentate base such as DABCO.1 Using a similar strategy as the one used in antisense research, an artificial nucleotidic backbone was built from modified deoxy-uridine units linked with a more rigid linker than the phosphodiester moieties found in natural oligonucleotides. Antisense research uses modified oligonucleotides, less flexible than natural strands, to pre-organize the system toward the obtaining of stable double helices between synthesized and natural oligonucleotides. A modified oligonucleotidic backbone was here used to target a parallel conformation of the porphyrins appended to each deoxy-uridine moiety. To provide a rigid environment for the porphyrins, the uridine units were coupled in 3’-5’ stepwise fashion using ether-ester type of spacer of suitable length, and porphyrins were anchored to the uridine by means of robust carbon-carbon bonds. Earlier studies demonstrated that a peptidic linker doesn’t provide sufficient pre-organization to enhance significantly the association constant with bidentate bases such as DABCO on the contrary of some flexible linkers such as uridine or 2’-deoxyuridine. We document herein that the gain in stability for the formation of sandwich type host-guest complex with DABCO can be even greater when a dinucleotide linker is used. Such pre-organization increases the association constants by one to two orders of magnitude when compared to the association constants of the same bidentate ligands with a reference Zn(II) porphyrin. Comparison of these results with those obtained for rigid tweezers shows a better efficiency of the flexible nucleosidic dimers. We thus document the fact that the choice of rigid spacers is not the only way to pre-organize bis-porphyrins, and that some well-chosen nucleosidic linkers offer an interesting option for the synthesis of such devices. Furthermore, the chirality and enantio-purity of the nucleosidic linkers paves the way toward the selective complexation of enantio-pure bidentate guests and the resolution of racemates. Acknowledgements This work was supported by the CNRS and the French Ministry of Research. References S. Merkas, S. Bouatra, R. Rein, I. Piantanida, M. Zinic, N. Solladié, J. Porphyrins Phthalocyanines 2015, 19, 535-546. Figure 1

Photochromic 1,2-bis(2′-methyl-5′-(carboxylic acid)-3′-thienyl) perfluorocyclopentene and its Co(II) coordination polymer

Crystallization from methanol of 1,2-bis(2′-methyl-5′-(carboxylic acid)-3′-thienyl)perfluorocyclopentene (BM-5-CATP, H2L) afforded a new single crystal (H2LMeOH) characterized by single crystal X-ray diffraction analysis, whose structure is different from those of the known crystals crystallized from ethanol, acetone/hexane or acetonitrile. There are two independent molecules with different conformations in one asymmetric unit of H2L. One is a photo-active anti-parallel conformation in which the reactive C atoms are separated by 3.90Å whereas the other is a photo-inactive parallel conformation in which the reactive C-C distance is 4.42Å. The packing characteristics of the two structures derived from methanol and ethanol were compared and analyzed in detail helped by the corresponding computational analyses. The photo-isomerizations of H2LMeOH in tetrahydrofuran and in solid state occur reversibly upon alternate irradiation with ultraviolet (λ=254nm) and visible light (λ>550nm).Reaction of CoCl2·6H2O with BM-5-CATP in methanol afforded a new complex [CoL(MeOH)4](MeOH) (1). Complex 1 is revealed by X-ray crystal diffraction as a 1D zigzag chain, where BM-5-CATP serves as bis-monodentate ligand bridging Co(II) centers in syn-anti fashion. The two thienyl rings in 1 adopt anti-parallel fashions and the distances of 3.80Å between two reactive carbons is short enough for the occurrence of photocyclizations. As expect, complex 1 displayed effective photo-isomerization in crystalline phase with color interconversion between pink and purple, indicating weak suppression of photochromism from metal coordination and extensive H bonds as well as Van de Waals contacts. The λmax of 1 (580nm) in closed form shifted to longer wavelength compared with that of free ligand (576nm).

Structural switch from a multistranded G-quadruplex to single strands as a consequence of point mutation in the promoter of the human GRIN1 gene.

A huge number of G-rich sequences forming quadruplexes are found in the human genome, especially in telomeric regions, UTRs, and the promoter regions of a number of genes. One such gene is GRIN1 encoding the NR1 subunit of the N-methyl-d-aspartate receptor (NMDA). Several lines of reports have implicated that attenuated function of NMDA results in schizophrenia, a genetic disorder characterized by hallucinations, delusions, and psychosis. Involvement of the GRIN1 gene in the pathogenesis of schizophrenia has been extensively analysed. Recent reports have demonstrated that polymorphism in the promoter region of GRIN1 at position -855 (G/C) has a possible association with schizophrenia. The binding site for the NF-κB transcription factor gets altered due to this mutation, resulting in reduced gene expression as well as NMDA activity. By combining gel electrophoresis (PAGE), circular dichroism (CD) and CD melting techniques, the G → C single nucleotide polymorphism (SNP) at the G-rich sequence (d-CTTAGCCCGAGGAG[combining low line]GGGGGTCCCAAGT; GRIN1) was investigated. We report that the GRIN1 sequence can form an octameric/multistranded quadruplex structure with parallel conformation in the presence of K+ as well as Na+. CD and gel studies are in good correlation in order to detect molecularity and strand conformation. The parallel G-quadruplex species was hypothesized to be octameric in K+/Na+ salts. The mutated sequence (d-CTTAGCCCGAGGAC[combining low line]GGGGGTCCCAAGT; GRIN1M) remained single stranded under physiological conditions. CD melting studies support the formation of an interstranded G-quadruplex structure by the GRIN1 sequence. Two structural models are propounded for a multistranded parallel G-quadruplex conformation which might be responsible for regulating the gene expression normally underlying memory and learning.

Light-induced oxidation of the telomeric G4 DNA in complex with Zn(II) tetracarboxymethyl porphyrin.

Structure-specific ligands are convenient tools for the recognition, targeting or probing of non-canonical DNA structures. Porphyrin derivatives exhibit a preference for interaction with G-quadruplex (G4) structures over canonical duplex DNA and are able to cause photoinducible damage to nucleic acids. Here, we show that Zn(II) 5,10,15,20-tetrakis(N-carboxymethyl-4-pyridinium)porphyrin (ZnP1) interacts with different conformations of the telomeric sequence d(TAGGG(TTAGGG)3) at submicromolar concentrations without any detectible disturbance of the particular fold. Among different folds, potassium (3+1) hybrid G4-structure. reveal the highest affinity to ZnP1. The pattern of guanine oxidation is specific for each telomeric DNA conformation and may serve as an additional tool for probing the G4 topology. The potassium (3+1) and parallel G4 conformations are more susceptible to light-induced oxidation than the sodium G4 conformation or double helix of the telomeric DNA. The major products of the guanine modifications are spiroiminodihydantoin (Sp) and 8-oxoguanine (8-oxoG). ZnP1-induced oxidation of guanines results in the structural rearrangement of parallel and (3+1) G4 conformations yielding an antiparallel-like G4 conformation. The mechanism of the observed light-induced conformational changes is discussed.

Spectroscopic investigation of the interaction between G-quadruplex of KRAS promoter sequence and three isoquinoline alkaloids

KRAS promoter can form G-quadruplex structure and regulate gene transcription. The drugs which can bind with G-quadruplex of KRAS promoter may be potential remedy for treatment of cancers associated with KRAS mutation. The interaction mechanism between the G-quadruplex of KRAS promoter and three isoquinoline alkaloids (jatrorrhizine, berberine and sanguinarine) has been investigated by UV-visible, fluorescence and circular dichroism spectroscopic methods. The results showed that the three alkaloids can form complexes with G-quadruplex KRAS promoter with the molecular ratio of 1:1, and the binding constants were (0.90±0.16)×106Lmol−1, (0.93±0.21)×106Lmol−1 and (1.16±0.45)×106Lmol−1 for jatrorrhizine, berberine and sanguinarine. The absorption spectra, KI quenching and fluorescence anisotropy and polarization studies suggested jatrorrhizine and berberine interacted with G-quadruplex by not only end-stacking binding mode but also grooves or loops binding mode, while sanguinarine by end-stacking binding mode. Sanguinarine was more beneficial to maintain the stability and parallel conformation of KRAS promoter G-quadruplex. MTT assay was performed to evaluate antiproliferation effects of the three isoquinoline alkaloids on SW620 cells, and the antiproliferation effects of the three alkaloids were sanguinarine > berberine > jatrorrhizine. All the three alkaloids can bind with KRAS promoter G-quadruplex, and sanguinarine had the better binding property and antiproliferation effects on SW620 cells. The results obtained are meaningful to explore potential reagents targeting the parallel G-quadruplex structure of KRAS promoter for gene theraphy of colorectal carcinomas.

Ferrocene‐Grafted Photochromic Triads Based on a Sterically Hindered Ethene Bridge: Redox‐Switchable Fluorescence and Gated Photochromism

Multifunctional switches, as well as gated photochromism, are particularly challenging. Here, a ferrocene (Fc)‐modified photochromic diarylethene (DAE) with sterically hindered ethene bridge, in which the photo‐inactive parallel conformer and photoactive antiparallel conformer are individually investigated, is reported. The photoswitchable triad system (parallel conformer p‐Fc and anti‐parallel ap‐Fc) contains three functional parts: photochromic DAE unit, naphthalimide chromophore, and redox‐active ferrocene. Upon incorporation of ferrocene unit, the photochromic efficiency in the anti‐parallel triad conformer ap‐Fc is blocked to a great extent in the ferrocene state but distinctly enhanced in the ferrocenium state via chemical or electrochemical stimuli, thereby constructing redox‐gated photochromism. Meanwhile, the reversible redox between ferrocene and ferrocenium states can also switch “OFF/ON” the fluorescence of naphthalimide chromophore via photoinduced electron transfer pathway (PET). The fluorescence and photoisomerization in the triad system are well modulated with chemical‐ or electrochemical redox and light stimuli, which enables the specific gated photochromism and fluorescence switches work in multi‐addressable states.

Polypeptides with Pendant Porphyrins: From the Recognition of Bidentate Bases to Inter-Digitated Photo-Active Strands

In natural photosynthetic systems, the solar energy is collected by pigment molecules attached to the light harvesting complexes. In these units, the chlorophylls are held in a favored spacing and orientation by fairly short a-helical polypeptides.1 When a photon hits one of the chlorophylls, the absorbed energy spreads extremely rapidly to the others until the reaction center is reached within the cell membrane, where the solar energy is converted into chemical energy used by the cell to grow. In this way, the energy contained in a single photon is conducted in a very short time and with minimal loss of energy from the point where it is absorbed to where it is needed. The extraordinary efficiency of the energy migration over long distances with minimal loss of energy is ascribed to the favored spacing and orientation of the chlorophylls which are held in an appropriate parallel conformation. Beyond the control of the structure of multi-chromophoric arrays, monitoring the spatial orientation of the chromophores in artificial light harvesting devices is a challenge of growing interest. Indeed, multi-porphyrinic arrays attract more and more attention for the elaboration of photonic and electronic wires.2 An octapeptide3 and an hexadecapeptide4 derived from the L-lysine and functionalized with porphyrins have been prepared. Beyond a certain degree of oligomerisation, we observed the development of a secondary structure such as a 310 helix which forces the porphyrins to arrange in a defined spatial arrangement. Due to the overlap of the porphyrins in such a conformation, the chromophores undergo a sufficient electronic coupling to favor a good exciton migration.5 The ability of these peptides to accomodate guests was investigated through ligand binding studies carried out in dichloromethane with DABCO as bidentate base. The complexation of DABCO by these peptides was monitored by UV-visible spectrophotometric titration in CH2Cl2. We showed that the enhanced stability of the complexe octapeptide/DABCO can be ascribed to a pre-organization of the octapeptide forming cavities, and provides convincing evidence that the bidentate base is inserted into the cavities of the octapeptide via host/guest interactions. Acknowledgements This work was supported by the CNRS and the French Ministry of Research. References W. Kühlbrandt, Nature 1995, 374, 497-498.a) R. W. Wagner, J. S. Lindsey, J. Seth, V. Palaniappan, D. F. Bocian, J. Am. Chem. Soc. 1996, 118, 3996-3997 and ref. cited therein. b) M. J. Crossley, P. L. Burn, S. J. Langford, J. K Prashar, J. Chem. Soc., Chem. Commun. 1995, 1921-1923. c) A. Osuka, H. Shimidzu, Angew. Chem. Int. Ed. Engl. 1997, 36, 135-137. N. Solladié, A. Hamel, M. Gross, Tet. Lett. 2000, 41, 6075-6078.Unpublished results.a) M. Fujitsuka, M. Hara, S. Tojo, A. Okada, V. Troiani, N. Solladié, T. Majima, J. Phys. Chem B. 2005, 109, 33-35. b) M. Fujitsuka, D. W. Cho, N. Solladié, V. Troiani, H. Qiu, T. Majima, J. Photochem. Photobiol. A 2007, 188, 346-350. Figure 1

(Invited) Pre-Organized Dinucleosides with Pendant Porphyrins for the Formation of Sandwich Type Complexes with DABCO with High Association Constants

Chemistry “beyond the molecule” is epitomized in nature by a plethora of relatively weak noncovalent interactions. The three-dimensional structures of most biopolymers are controlled with noncovalent interactions, either between different parts of the same strand (as in protein α-helices) or between two separate strands (as in the DNA duplex and protein β-sheet). While nature has refined the construction of biopolymers, our mastery of the subtle noncovalent interactions as synthetic tools is in an early stage of development. Only in the past two decades people begun to develop ways of mimicking the natural light-harvesting complexes by noncovalent assembly of porphyrin units aiming to obtain favored spacing and orientation between the chromophores. The construction of multi-chromophoric assemblies has led to resurgence of interest in coordination chemistry due to formation of ordered arrays directed through molecular recognition events. As a module in the construction of supramolecular assemblies, porphyrins and metallo-porphyrins can be exploited in two different ways: porphyrins can behave as donor building blocks insofar as they comprise meso-substituents, such as pyridyl groups, which can act as ligands that can suitably coordinate to metal cations, while metalloporphyrins can act as acceptor building blocks as soon as the metal atom inside the porphyrin core has at least one axial site available for coordination. For the last years, we have focussed on cofacial bis-porphyrin tweezers for host/guest interactions and investigated the possibilty to obtain self-coordinated molecular systems with predictable spectral and redox characteristics. We report here the synthesis of a di-nucleotide bearing pendant porphyrins dedicated to adopt a pre-organized coformation with face-to-face porphyrins, and capable to self-organize in a stable sandwich type complexe with bidentate base such as DABCO.1 Using a similar strategy as the one used in antisense research, an artificial nucleotidic backbone was built from modified deoxy-uridine units linked with a more rigid linker than the phosphodiester moieties found in natural oligonucleotides. Antisense research uses modified oligonucleotides, less flexible than natural strands, to pre-organize the system toward the obtaining of stable double helices between synthesized and natural oligonucleotides. A modified oligonucleotidic backbone was here used to target a parallel conformation of the porphyrins appended to each deoxy-uridine moiety. To provide a rigid environment for the porphyrins, the uridine units were coupled in 3’-5’ stepwise fashion using ether-ester type of spacer of suitable length, and porphyrins were anchored to the uridine by means of robust carbon-carbon bonds. Earlier studies demonstrated that a peptidic linker doesn’t provide sufficient pre-organization to enhance significantly the association constant with bidentate bases such as DABCO on the contrary of some flexible linkers such as uridine or 2’-deoxyuridine. We document herein that the gain in stability for the formation of sandwich type host-guest complex with DABCO can be even greater when a dinucleotide linker is used. Such pre-organization increases the association constants by one to two orders of magnitude when compared to the association constants of the same bidentate ligands with a reference Zn(II) porphyrin. Comparison of these results with those obtained for rigid tweezers shows a better efficiency of the flexible nucleosidic dimers. We thus document the fact that the choice of rigid spacers is not the only way to pre-organize bis-porphyrins, and that some well-chosen nucleosidic linkers offer an interesting option for the synthesis of such devices. Furthermore, the chirality and enantio-purity of the nucleosidic linkers paves the way toward the selective complexation of enantio-pure bidentate guests and the resolution of racemates. Acknowledgements This work was supported by the CNRS and the French Ministry of Research. References S. Merkas, S. Bouatra, R. Rein, I. Piantanida, M. Zinic, N. Solladié, J. Porphyrins Phthalocyanines 2015, 19, 535-546. Figure 1

A Water-Soluble Tetraazaperopyrene Dye as Strong G-Quadruplex DNA Binder.

The interactions of the water‐soluble tetraazaperopyrene dye 1 with ct‐DNA, duplex‐[(dAdT)12 ⋅(dAdT)12], duplex‐[(dGdC)12 ⋅(dGdC)12] as well as with two G‐quadruplex‐forming sequences, namely the human telomeric 22AG and the promotor sequence c‐myc, were investigated by means of UV/visible and fluorescence spectroscopy, isothermal titration calorimetry (ITC) and molecular docking studies. Dye 1 exhibits a high affinity for G‐quadruplex structures over duplex DNA structures. Furthermore, the ligand shows promising G‐quadruplex discrimination, with an affinity towards c‐myc of 2×107 m −1 (i.e., K d=50 nm), which is higher than for 22AG (4×106 m −1). The ITC data reveal that compound 1 interacts with c‐myc in a stoichiometric ratio of 1:1 but also indicate the presence of two identical lower affinity secondary binding sites per quadruplex. In 22AG, there are two high affinity binding sites per quadruplex, that is, one on each side, with a further four weaker binding sites. For both quadruplex structures, the high affinity interactions between compound 1 and the quadruplex‐forming nucleic acid structures are weakly endothermic. Molecular docking studies suggest an end‐stacking binding mode for compound 1 interacting with quadruplex structures, and a higher affinity for the parallel conformation of c‐myc than for the mixed‐hybrid conformation of 22AG. In addition, docking studies also suggest that the reduced affinity for duplex DNA structures is due to the non‐viability of an intercalative binding mode.

Systematic and Quantitative Analysis of G-Quadruplex DNA Folding

G-quadruplex (GQ) is a noncanonical secondary structure that forms in G-rich sequences of DNA or RNA. GQ has been implicated in gene regulation and human diseases, yet its biological role is still unclear. We sought to investigate the folding propensity of potential GQ forming sequences and measure the GQ folding strength in a systematic and quantitative manner. We prepared over 400 GQ forming sequences by modulating the loop length and sequence composition within the context of [G3 N G3 N G3 N G3] where “N” represents the loop. First, we used the induced fluorescence of N-methyl mesoporphrin IX (NMM) (1) to quantify the parallel conformation of GQ folding in both single (ss) and double stranded (ds) DNA. Second, we established DNA polymerization (DNAP) assay in which tight GQ folding inhibits DNA extension. The folding stability measured by DNAP showed a high correlation to the NMM fluorescence observed in ssDNA, suggesting that parallel conformation is likely responsible for the GQ folding strength. Third, we employed in vitro transcription assay in which mRNA synthesis is detected in real time. Taken together, we provide quantitative biochemical and biophysical platforms to profile GQ folding sequences in DNA and RNA.1. Kreig, A., Calvert, J., Sanoica, J., Cullum, E., Tipanna, R. and Myong, S. (2015) G-quadruplex formation in double strand DNA probed by NMM and CV fluorescence. Nucleic Acids Res.

A label-free electrochemical sensor for detection of mercury(II) ions based on the direct growth of guanine nanowire

A simple, sensitive and label-free electrochemical sensor is developed for detection of Hg2+ based on the strong and stable T–Hg2+–T mismatches. In the presence of Mg2+, the parallel G-quadruplex structures could be specifically recognized and precipitated in parallel conformation. Therefore, the guanine nanowire was generated on the electrode surface, triggering the electrochemical H2O2-mediated oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB). In this research, a new method of signal amplification for the quantitative detection of Hg2+ was described based on the direct growth of guanine nanowire via guanine nanowire. Under optimum conditions, Hg2+ was detected in the range of 100pM–100nM, and the detection limit is 33pM. Compared to the traditional single G-quadruplex label unit, this electrochemical sensor showed high sensitivity and selectivity for detecting Hg2+.

Aggregation induced emission from α-napthoflavone microstructures and its cyto-toxicity

α-Napthoflavone (ANF) microstructures of various morphologies were synthesized using reprecipitation method. Sodium Dodecyl Sulfate (SDS) was used as morphology directing agent. The morphologies of the particles were characterized using optical and scanning electron microscopy (SEM). Single crystal data of ANF suggests that the aromatic units of ANF are in parallel slipped conformation in its aggregated form. Photophysical properties of aggregated ANF hydrosol were studied using UV–Vis absorption, steady state and time resolved spectroscopy. Red shift and broadening of UV–Vis spectra of ANF hydrosol are explained due to strong π-π and H-π interactions among the neighboring ANF molecules within the aggregated microstructures. Though ANF is non-luminescent in good solvent, a strong emission is observed in its aggregated state. This aggregation induced emission (AIE) has been explained due to restriction of intramoleculer rotation and large amplitude vibrational modes of ANF in its aggregated state. Our Photophysical study also reveals that AIE effect decreases after an optimum concentration of ANF and this has been explained due to softening of crystal lattice. Cytotoxicity of ANF hydrosol was examined to get an idea of the toxic level of this hydrosol toward cultured normal human cells. It is observed that ANF hydrosol may draw beneficial effect in biological application as it has no higher toxic activity but has antioxidant property.

Crystal induced phosphorescence from Benz(a)anthracene microcrystals at room temperature

Pure organic compounds that are also phosphorescent at room temperature are very rare in literature. Here, we report efficient phosphorescence emission from aggregated hydrosol of Benz(a)anthracene (BaA) at room temperature. Aggregated hydrosol of BaA has been synthesized by re-precipitation method and SDS is used as morphology directing agent. Morphology of the particles is characterized using optical and scanning electronic microcopy (SEM). Photophysical properties of the aggregated hydrosol are carried out using UV–vis, steady state and time resolved fluorescence study. The large stoke shifted structured emission from aggregated hydrosol of BaA has been explained due to phosphorescence emission of BaA at room temperature. In the crystalline state, the restricted intermolecular motions (RIM) such as rotations and vibrations are activated by crystal lattice. This rigidification effect makes the chromophore phosphorescent at room temperature. The possible stacking arrangement of the neighboring BaA within the aggregates has been substantiated by computing second order Fukui parameter as local reactivity descriptors. Computational study also reveals that the neighboring BaA molecules are present in parallel slipped conformation in its aggregated crystalline form.

Impact of Strand Number on Parallel β-Sheet Stability.

We have examined whether parallel β-sheet secondary structure becomes more stable as the number of β-strands increases, via comparisons among peptides designed to adopt two- or three-stranded parallel β-sheet conformations in aqueous solution. Our three-strand design is the first experimental model of a triple-stranded parallel β-sheet. Analysis of the designed peptides by nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy supports the hypothesis that increasing the number of β-strands, from two to three, increases the stability of the parallel β-sheet. We present the first experimental evidence for cooperativity in the folding of a triple-stranded parallel β-sheet, and we show how minimal model systems may enable experimental documentation of characteristic properties, such as CD spectra, of parallel β-sheets.

Resonance photoionization of a diarylethene derivative in the presence of cyclodextrins using multi-color multi-laser irradiation

Abstract Photochromism is isomerization of a molecule induced by light, and is attractive for applications like actuators and optical memory. However, the photodynamics of photochromic materials under excitation by three lasers at three different wavelengths are poorly understood. In this article, we investigate the properties of the well-known photochromic material 2,3-bis(2,4,5-trimethyl-3-thienyl) maleic anhydride (1) upon excitation by one, two and three lasers. In these experiments, α-, β- and γ-cyclodextrin (CD) are added to 1 to form inclusion complexes to improve the solubility of 1 in water/acetonitrile. First, the formation of 1/CD inclusion complexes is evaluated by changes in the 1H NMR spectrum of 1 and calculations. We find that the area of each molecule of 1 in the 1/CD inclusion complexes exposed to the solvent depends on the cavity size of the CD, and that the CD also affects the ratio of the antiparallel and parallel conformations of the open form (OP) of 1. The transient absorption of hydrated electrons in the 1/CD systems is then observed at 720 nm by flash photolysis using one laser (266 nm), two lasers (266 and 532 nm) and three lasers (266, 532 and 355 nm). The ionization quantum yields of 1 depend on both the type of CD present, which is rationalized by the ability of 1 to isomerize in the different-sized cavities of α-, β- and γ-CD, and on the laser pulse configuration. The ionization efficiency obtained using the two-laser system is higher than that measured with the one-laser system. This confirms that two-photon ionization of 1 proceeds through two-step two-photon excitation with S0 → S1 and S1 → Sn singlet-state transitions. The photoionization efficiency of 1 in the presence of CDs determined using three laser pulses increases upon opening of the closed-ring isomer (CL) of 1 by 532 nm irradiation (the second laser pulse). This effect is particularly obvious in the presence of γ-CD. This investigation of the photodynamics of 1 in inclusion complexes using multiple lasers contributes to our understanding of how we can influence photochromism using host species and different laser wavelengths.

Polypeptides with Pendant Porphyrins: From the Recognition of Bidentate Bases to Inter-Digitated Photo-Active Strands

In natural photosynthetic systems, the solar energy is collected by pigment molecules attached to the light harvesting complexes. In these units, the chlorophylls are held in a favored spacing and orientation by fairly short α-helical polypeptides.1 When a photon hits one of the chlorophylls, the absorbed energy spreads extremely rapidly to the others until the reaction center is reached within the cell membrane, where the solar energy is converted into chemical energy used by the cell to grow. In this way, the energy contained in a single photon is conducted in a very short time and with minimal loss of energy from the point where it is absorbed to where it is needed. The extraordinary efficiency of the energy migration over long distances with minimal loss of energy is ascribed to the favored spacing and orientation of the chlorophylls which are held in an appropriate parallel conformation. Beyond the control of the structure of multi-chromophoric arrays, monitoring the spatial orientation of the chromophores in artificial light harvesting devices is a challenge of growing interest. Indeed, multi-porphyrinic arrays attract more and more attention for the elaboration of photonic and electronic wires.2 An octapeptide3 and an hexadecapeptide4 derived from the L-lysine and functionalized with porphyrins have been prepared. Beyond a certain degree of oligomerisation, we observed the development of a secondary structure such as a 310 helix which forces the porphyrins to arrange in a defined spatial arrangement. Due to the overlap of the porphyrins in such a conformation, the chromophores undergo a sufficient electronic coupling to favor a good exciton migration.5 The ability of these peptides to accomodate guests was investigated through ligand binding studies carried out in dichloromethane with DABCO as bidentate base. The complexation of DABCO by these peptides was monitored by UV-visible spectrophotometric titration in CH2Cl2. We showed that the enhanced stability of the complexe octapeptide/DABCO can be ascribed to a pre-organization of the octapeptide forming cavities, and provides convincing evidence that the bidentate base is inserted into the cavities of the octapeptide via host/guest interactions. Acknowledgements This work was supported by the CNRS and the French Ministry of Research. References W. Kühlbrandt, Nature 1995, 374, 497-498.a) R. W. Wagner, J. S. Lindsey, J. Seth, V. Palaniappan, D. F. Bocian, J. Am. Chem. Soc. 1996, 118, 3996-3997 and ref. cited therein. b) M. J. Crossley, P. L. Burn, S. J. Langford, J. K Prashar, J. Chem. Soc., Chem. Commun. 1995, 1921-1923. c) A. Osuka, H. Shimidzu, Angew. Chem. Int. Ed. Engl. 1997, 36, 135-137. N. Solladié, A. Hamel, M. Gross, Tet. Lett. 2000, 41, 6075-6078.Unpublished results.a) M. Fujitsuka, M. Hara, S. Tojo, A. Okada, V. Troiani, N. Solladié, T. Majima, J. Phys. Chem B. 2005, 109, 33-35. b) M. Fujitsuka, D. W. Cho, N. Solladié, V. Troiani, H. Qiu, T. Majima, J. Photochem. Photobiol. A 2007, 188, 346-350. Figure 1

Nucleotidic and Peptidic Multi-Porphyrinic Devices: When the Desired Conformation Is Determined By Chiral Flexible Linkers

In natural photosynthetic systems, the solar energy is collected by pigment molecules attached to the light harvesting complexes. In these units, the chlorophylls are held in a favored spacing and orientation by fairly short α-helical polypeptides.1 When a photon hits one of the chlorophylls, the absorbed energy spreads extremely rapidly to the others until the reaction center is reached within the cell membrane, where the solar energy is converted into chemical energy used by the cell to grow. In this way, the energy contained in a single photon is conducted in a very short time and with minimal loss of energy from the point where it is absorbed to where it is needed. The extraordinary efficiency of the energy migration over long distances with minimal loss of energy is ascribed to the favored spacing and orientation of the chlorophylls which are held in an appropriate parallel conformation. Beyond the control of the structure of multi-chromophoric arrays, monitoring the spatial orientation of the chromophores in artificial light harvesting devices is a challenge of growing interest. Indeed, multi-porphyrinic arrays attract more and more attention for the elaboration of photonic and electronic wires.2 An octapeptide3 and an hexadecapeptide4 derived from the L-lysine and functionalized with porphyrins have been prepared. Beyond a certain degree of oligomerisation, we observed the development of a secondary structure such as a 310 helix which forces the porphyrins to arrange in a defined spatial arrangement. Due to the overlap of the porphyrins in such a conformation, the chromophores undergo a sufficient electronic coupling to favor a good exciton migration.5 The ability of these peptides to accomodate guests was investigated through ligand binding studies carried out in dichloromethane with DABCO as bidentate base. The complexation of DABCO by these peptides was monitored by UV-visible spectrophotometric titration in CH2Cl2. We showed that the enhanced stability of the complexe octapeptide/DABCO can be ascribed to a pre-organization of the octapeptide forming cavities, and provides convincing evidence that the bidentate base is inserted into the cavities of the octapeptide viahost/guest interactions. We also investigated the ability of oligonucleotides to orientate porphyrins in space, and the capability of this type of backbone to generate multi-porphyrinic hosts able to complex multiple bidentate guests. Acknowledgements This work was supported by the CNRS and the French Ministry of Research. References W. Kühlbrandt, Nature 1995, 374, 497-498.a) R. W. Wagner, J. S. Lindsey, J. Seth, V. Palaniappan, D. F. Bocian, J. Am. Chem. Soc. 1996, 118, 3996-3997 and ref. cited therein. b) M. J. Crossley, P. L. Burn, S. J. Langford, J. K Prashar, J. Chem. Soc., Chem. Commun. 1995, 1921-1923. c) A. Osuka, H. Shimidzu, Angew. Chem. Int. Ed. Engl. 1997, 36, 135-137. N. Solladié, A. Hamel, M. Gross, Tet. Lett. 2000, 41, 6075-6078.Unpublished results.a) M. Fujitsuka, M. Hara, S. Tojo, A. Okada, V. Troiani, N. Solladié, T. Majima, J. Phys. Chem B. 2005, 109, 33-35. b) M. Fujitsuka, D. W. Cho, N. Solladié, V. Troiani, H. Qiu, T. Majima, J. Photochem. Photobiol. A 2007, 188, 346-350. Figure 1