The yellow-green light emitted by fireflies is one of the most prominent examples of bioluminescence. Firefly oxyluciferin, the emitting molecule, is labile in alkaline solutions, and its structure is strongly affected by solvent polarity and pH. Previous studies have suggested that variations in the active site conditions are likely contributors to the color of bioluminescent emission. Herein, we incorporate firefly oxyluciferin into an agarose matrix to emulate the enzyme active site. Self-supporting, lightweight thin films were fabricated by solution casting and spectroscopically characterized. The previously described acidochromism of oxyluciferin is conserved in the thin films. The bathochromic shift observed in alkaline conditions results from the formation of the oxyluciferin dianion. This study demonstrates an alternative approach to investigating environmental effects on bioluminescent molecules.
The thermosalient behavior of 1,2,4,5-tetrabromobenzene (TBB) is related to a temperature-induced polymorphic structural change. The mechanism behind the phase transition has been investigated in this work using low-frequency (10–250 cm−1) Raman spectroscopy and solid-state density functional theory simulations. Careful adjustments of the probing laser power permitted thermal control of the polymorph populations and enabled high-quality Raman vibrational spectra to be obtained for both the β (low temperature) and γ (high temperature) forms of TBB. Numerous well-defined vibrational features appear in the Raman spectra of both polymorphs which could be assigned to specific motions of the solid-state TBB molecules. It was discovered that the lowest-frequency vibration at 15.5 cm−1 in β-TBB at 291 K is a rotational mode that functions as a gateway for inducing the polymorphic phase transition to γ-TBB, and serves as the initiating step in the storage of mechanical strain for subsequent macroscopic release. Computationally mapping the potential energy surface along this vibrational coordinate reveals that the two TBB polymorphs are separated by a 2.40 kJ mol−1 barrier and that γ-TBB exhibits an enhanced cohesion energy that stabilizes its structure.
The photochemical conversion of 1,8a‐dihydroazulene‐1,1‐dicarbonitrile (DHA) to vinylheptafulvene (VHF) is a positive T‐type photoswitch that is well understood in solution, but has not been explored in the solid state. Upon excitation with UV light, DHA is converted into VHF in the solid state, with a distinct color change from yellow to deep‐red, and retention of crystallinity. The structure of the ring‐opened product was assigned to syn‐VHF using variable‐temperature infrared spectroscopy, and determined by X‐ray photodiffraction in a crystal enriched with the product by two‐photon excitation. A radical pathway becomes an observable photoreaction channel at low temperatures, and includes a strongly colored, short‐lived diradical intermediate.
An anthracene derivative, 9,10‐dicyanoanthracene, crystallizes as fluorescent needle‐like single crystals that can be readily plastically bent in two directions. Spatially resolved photoluminescence analysis revealed that this material has robust optoelectronic properties that are preserved upon extreme crystal deformation. The highly flexible crystals were successfully tested as efficient switchable optical waveguiding elements for both active and passive light transduction, and the mode of operation depends on the wavelength of the incident light. This prototypical dual‐mode organic optical crystalline fiber brings mechanically compliant molecular organic crystals closer to applications as novel light‐transducing media for wireless transfer of information in all‐organic micro‐optoelectronic devices.
We report the first example of a simple, yet robust, reproducible and scalable method for direct conversion of sodium alginate (SA) films to multibranched hydrogel tubes (HTs) in “one-pot” reaction of buffered aqueous solution. This method allows for construction of branched hollow HTs of any shape and arbitrary size, and enables further functionalization for application requirements.
The different colors of light emitted by bioluminescent beetles that use an identical substrate and chemiexcitation reaction sequence to generate light remain a challenging and controversial mechanistic conundrum. The crystal structures of two beetle luciferases with red- and blue-shifted light relative to the green yellow light of the common firefly species provide direct insight into the molecular origin of the bioluminescence color. The structure of a blue-shifted green-emitting luciferase from the firefly Amydetes vivianii is monomeric with a structural fold similar to the previously reported firefly luciferases. The only known naturally red-emitting luciferase from the glow-worm Phrixothrix hirtus exists as tetramers and octamers. Structural and computational analyses reveal varying aperture between the two domains enclosing the active site. Mutagenesis analysis identified two conserved loops that contribute to the color of the emitted light. These results are expected to advance comparative computational studies into the conformational landscape of the luciferase reaction sequence.
The first example of a smart crystalline material, the 2:1 cocrystal of probenecid and 4,4′‐azopyridine, which responds reversibly to multiple external stimuli (heat, UV light, and mechanical pressure) by twisting, bending, and elastic deformation without fracture is reported. This material is also able to self‐heal on heating and cooling, thereby overcoming the main setbacks of molecular crystals for future applications as crystal actuators. The photo‐ and thermomechanical effects and self‐healing capabilities of the material are rooted in reversible trans–cis isomerization of the azopyridine unit and crystal‐to‐crystal phase transition. Fairly isotropic intermolecular interactions and interlocked crisscrossed molecular packing secure high elasticity of the crystals.
A bioinspired fluorophore that is analogous to the substrate in the bioluminescence of fireflies was prepared and reacts when exposed to weak blue LED light. Upon excitation, this material is photodecarboxylated with a nearly 81‐fold enhancement of the solid‐state emission, the fluorescence quantum yield of the product in solution is approximately 90 %, and violent disintegrative effects occur as a result of the release of carbon dioxide. Crystallographic and computational results, together with global spectral analysis of the kinetics, confirmed that most of the emission observed in the decay‐associated spectra is intrinsic to the product molecule, with only a minor contribution from an excimer through π–π stacking of the molecules in the crystal.
Ischemic heart disease often leads to myocardial infarction and remains the most common cause for death in humans. Although the exact impetus for the infarction remains elusive, a mechanism has been proposed that relates the disease to the observed high cholesterol levels in the body. The mechanism claims that cholesterol crystallizes inside the arterial plaque into needle‐shaped crystals. The crystals puncture the fibrous cap of the plaque, whereby the necrotic contents of the plaque are spilled, subsequently clotting the blood vessels. This hypothesis has not been given sufficient attention partly due to the purported softness of the organic crystals and the common platy habit of the known crystal forms of cholesterol. In this work it is shown that, from hydrophobic solutions that attempt to emulate the plaque contents, a new solid form of cholesterol crystallizes as prisms with mucronate tips, and they are sufficiently strong to puncture a lamb pericardium, which mimics the plaque cap. The properties of the crystals were assessed by mechanical, structural, and crystallographic analyses. The results support the hypothesis that the cholesterol crystals can be considered, at least within the framework of the proposed mechanism, a possible cause of myocardial infarction.
Mechanically reconfigurable molecular crystals—ordered materials that can adapt to variable operating and environmental conditions by deformation, whereby they attain motility or perform work—are quickly shaping a new research direction in materials science, crystal adaptronics. Properties such as elasticity, superelasticity, and ferroelasticity, which are normally related to inorganic materials, and phenomena such as shape‐memory and self‐healing effects, which are well‐established for soft materials, are increasingly being reported for molecular crystals, yet their mechanism, quantification, and relation to the crystal structure of organic crystals are not immediately apparent. This Minireview provides a condensed topical overview of elastic, superelastic, and ferroelastic molecular crystals, new classes of materials that bridge the gap between soft matter and inorganic materials. The occurrence and detection of these unconventional properties, and the underlying structural features of the related molecular materials are discussed and highlighted with selected prominent recent examples.
Various aspects of molecular motion in crystals have been extensively studied in different research fields of chemistry as a valuable source of structural and dynamic information en route to new smart materials and solid-state molecular machines. The recent research efforts are directed towards engineering crystalline media with specific motile components, namely amphidynamic crystals, whose dynamics can be exploited to achieve specific functions such as sensing, gas separation and switchable dielectrics. The most promising structural models within this line of pursuit are based upon anisotropic Brownian rotary trajectories. In this highlight, we review the recent advances in this field, with particular emphasis on potential applications. The summary should provide useful guidelines for further development of this remarkable class of materials.
Protein fibrillation is involved in many serious diseases, and protein oligomers are proved to be precursors of amyloid fibrils. NMR and QCMD experiments allowed us to establish that the interaction between citrate-stabilized gold nanoparticles and a paradigmatic amyloidogenic protein, β2-microglobulin, is able to interfere with protein association into oligomers.
Certain awns utilize actuating mechanisms that harness energy from variations in aerial humidity to self‐burrow their seeds into the soil. Here the morphokinematics of such hygroresponse from the awn of the feather grass Stipa epilosa is described. The elongated body of the awn is typically doubly bent, and has three segments with different functionalities: the long and stiff proximal segment twists reversibly to generate thrust for burrowing the seed, the plumose and flexible distal segment contributes to aerial dispersion, and the short and stiff middle segment provides a bent geometry for effective burial. Periodic variation in humidity results in expansion and twisting of individual cells, and the collective expansion generates a torque that drives reversible twisting of the proximal and middle segments.
The time course of photochemical solid-state reactions is routinely monitored by using spectroscopic methods such as NMR or IR spectroscopies, but is comparatively less investigated with thermal methods. In this work, a combination of thermal methods (thermogravimetric analysis and differential scanning calorimetry) was applied together with irradiation with UV light to quantify the conversion and monitor the progress of a well-known photochemical reaction, the [2 + 2] dimerization of trans-cinnamic acid, and the results are compared with the conversion determined by using 1H NMR spectroscopy. The conversion was correlated with thermodynamic parameters for the reactant such as molar enthalpy, entropy, and melting temperature.
The concept of biomineralization and encapsulation of organic molecules into inorganic matrices to alter and enhance their physical properties has been evolved and perfected in natural systems. Being inspired by the natural biomineralization of foreign components into calcite, here the inclusion of a plant virus, cowpea mosaic virus (CPMV) of 5.4% by mass into crystals of calcite is reported. The viral particles are labeled with a fluorescent tag (Alexa Fluor 532), and are observed within the calcite matrix using confocal fluorescence microscopy. Upon encapsulation, the calcite crystals exhibit an irregular and aggregated morphology, as visualized with atomic force and electron microscopy. The viral particles protected inside the calcite crystals are able to resist harsh chemical agents. While spherical viral particles such as CPMV can be easily included in calcite, viruses such as the tobacco mosaic virus are not compatible with the host, presumably due to their high aspect ratio. The results provide a simple and scalable method to incorporate viral particles into inorganic matrix, and could prove useful in thermal stabilization of sensitive viral biological agents such as vaccines in the future.
Latia neritoides is a small limpet‐like snail that produces a bright green bioluminescence (BL) via a unique light‐emitting system. The process, mechanism, and even light emitter of its light emission remain unknown, although this BL has been known for decades. Unlike the other BL systems, neither the luciferin (Luc) nor the oxyluciferin (OxyLuc) of Latia is fluorescent according to the previous experiments. To help to identify its bioluminophore, we studied the geometrical and electronic structures and absorption and fluorescence spectra of Latia Luc and its six analogs as well as its OxyLuc in the gas phase and in water. The calculated results provide clear evidence of the lack of fluorescence in the Luc and OxyLuc of Latia. For the analogs of Latia Luc, the electron‐withdrawing or electron‐donating ability of the substituted group affects the fluorescence. The results shed new light on the BL mechanism and will likely aid the understanding of Latia BL.
Bioluminescence is a phenomenon that has fascinated mankind for centuries. Today the phenomenon and its sibling, chemiluminescence, have impacted society with a number of useful applications in fields like analytical chemistry and medicine, just to mention two. In this review, a molecular-orbital perspective is adopted to explain the chemistry behind chemiexcitation in both chemi- and bioluminescence. First, the uncatalyzed thermal dissociation of 1,2-dioxetane is presented and analyzed to explain, for example, the preference for triplet excited product states and increased yield with larger nonreactive substituents. The catalyzed fragmentation reaction and related details are then exemplified with substituted 1,2-dioxetanone species. In particular, the preference for singlet excited product states in that case is explained. The review also examines the diversity of specific solutions both in Nature and in artificial systems and the difficulties in identifying the emitting species and unraveling the color modulation process. The related subject of excited-state chemistry without light absorption is finally discussed. The content of this review should be an inspiration to human design of new molecular systems expressing unique light-emitting properties. An appendix describing the state-of-the-art experimental and theoretical methods used to study the phenomena serves as a complement.
A single crystal of the cis-dimer of nitrosobenzene was directly observed by photocrystallography to transition to a pair of monomers and reversibly redimerize. The remarkable displacement of the nitrogen atoms within the crystal—moving a total distance of 2.97(5) Å for the two atoms—suggests that the breadth of solid-state photochemical reaction systems susceptible to X-ray diffraction studies need not be limited to those with very small atomic displacements.
An actuator driven by solar light is developed by incorporating an azo compound (F-Azo) into agarose (AG). The resulting F-Azo-doped AG (F-Azo@AG) films bend under sunlight irradiation. It is demonstrated that the sunlight-induced bending of the F-Azo@AG film transduces the sunlight into electricity when attached to a piezoelectric transducer.
Photomechanically reconfigurable elastic single crystals are the key elements for contactless, timely controllable and spatially resolved transduction of light into work from the nanoscale to the macroscale. The deformation in such single-crystal actuators is observed and usually attributed to anisotropy in their structure induced by the external stimulus. Yet, the actual intrinsic and external factors that affect the mechanical response remain poorly understood, and the lack of rigorous models stands as the main impediment towards benchmarking of these materials against each other and with much better developed soft actuators based on polymers, liquid crystals and elastomers. Here, experimental approaches for precise measurement of macroscopic strain in a single crystal bent by means of a solid-state transformation induced by light are developed and used to extract the related temperature-dependent kinetic parameters. The experimental results are compared against an overarching mathematical model based on the combined consideration of light transport, chemical transformation and elastic deformation that does not require fitting of any empirical information. It is demonstrated that for a thermally reversible photoreactive bending crystal, the kinetic constants of the forward (photochemical) reaction and the reverse (thermal) reaction, as well as their temperature dependence, can be extracted with high accuracy. The improved kinematic model of crystal bending takes into account the feedback effect, which is often neglected but becomes increasingly important at the late stages of the photochemical reaction in a single crystal. The results provide the most rigorous and exact mathematical description of photoinduced bending of a single crystal to date.
The pincer-like double ester naphthalene-2,3-diyl-bis(4-fluorobenzoate) (2) is pentamorphic. When crystals of form I are heated to below their melting point (441-443 K) they undergo a phase transition accompanied by a thermosalient effect, a rare and visually striking crystal motility whereby crystals jump or disintegrate. The phase transition and the thermosalient effect are reversible. Analysis of the crystal structure revealed that form I of 2 is a class II thermosalient solid. Crystals of form III also undergo a reversible phase transition in the temperature range 160-170 K, however they are not thermosalient. Comparison of the structures and the mechanical response between the two polymorphs reveals that the thermosalient effect of form I is due to reversible closing and opening of the arms of the diester molecules in a tweezers-like action.
Nanocrystals of the thermosalient (TS) material 1,2,4,5-tetrabromobenzene (TBB) with diameters of 20, 100,
and 200 nm were prepared by using nanoporous anodic aluminum oxide (AAO) templates. In contrast with bulk crystallization, which mainly affords single crystals of TBB in the stable phase β, two-dimensional X-ray microdiffraction revealed exclusive formation of polycrystalline TBB in the less stable phase γ inside the AAO nanopores. While bulk crystals of TBB undergo TS transition from phase β to γ at 41° C and melt at 180° C, the nanocrystals of phase γ TBB remain stable from cryogenic temperatures to nearly 80° C and sublime at higher temperature. This study reveals fundamentally different crystallization and thermal behavior of the TS materials at the nanoscale compared to the macroscale.
Latia neritoides is a small limpet-like snail that produces a bright green bioluminescence (BL) via a unique light-emitting system. The process, mechanism and even light emitter of its light emission remain unknown, although this BL has been known for decades. Unlike the other BL systems, neither the luciferin (Luc) nor the oxyluciferin (OxyLuc) of Latia is fluorescent according to the previous experiments. In order to help to identify its bioluminophore, we studied the geometrical and electronic structures and absorption and fluorescence spectra of Latia Luc and its six analogues as well as its OxyLuc in the gas phase and in water. The calculated results provide clear evidence of the lack of fluorescence in the Luc and OxyLuc of Latia. For the analogues of Latia Luc, the electron-withdrawing or electron-donating ability of the substituted group affects the fluorescence. The results shed new light on the BL mechanism and will likely aid the understanding of Latia BL.
Here we propose the combination of the 4-alkoxythiazole donor motif with highly photostable tetraazaanthracenes as electronacceptor units. The segregated frontier orbitals in these dyes afford optical band gaps of 1.4–1.1 eV. Cyclic voltammetry confirmed the very low-lying LUMO levels that are attributed to the highly electron-deficient tetraazaanthracene moiety.
2-Coumaranones are evolving as a new, efficient, versatile, and synthetically accessible platform for the next generation chemiluminescent probes. Despite the favorable quantum yields, the exact mechanism of their chemiluminescence remains elusive. Here, we analyze the details of the mechanism of the 2-coumaranone chemiluminescence using a combination of experimental and computational methods. By using EPR spectroscopy we show that superoxide radical anions are involved in the reactions, in support of the hypothesis that the mechanism includes a single electron transfer step. The decomposition of the high-energy intermediate, 1,2-dioxetanone, is described in the ground state and in the first three excited singlet states, and indicates that there is at least one conical intersection, which is crucial for generation of excited-state molecules. A peroxy anion that is generated was found to be able to undergo a side reaction that leads to the same (isolated) product as in the light-generating reaction. These results demonstrate the applicability of 2-coumaranones as a model system for several bioluminescence reactions and may lead to the design of new 2-coumaranone derivatives with superior emission characteristics for bioanalytical applications.
Silver-coated 1,2,4,5-tetrabromobenzene crystals, a thermosalient compound, are presented as novel electrical fuse materials. These electrically conductive crystals exhibit linear characteristics up to a threshold value where the resistive heating triggers their phase transformation. This causes mechanical motion of the crystals with immediate circuit breakage. The concept described here opens new avenues for next-generation electrical fuses.
Materials that respond rapidly and reversibly to external stimuli currently stand among the top choices as actuators for real-world applications. Here, a series of programmable actuators fabricated as single- or bilayer elements is described that can reversibly respond to minute concentrations of acetone vapors. By using templates, microchannel structures are replicated onto the surface of two highly elastic polymers, polyvinylidene fluoride (PVDF) and polyvinyl alcohol, to induce chiral coiling upon exposure to acetone vapors. The vapomechanical coiling is reversible and can be conducted repeatedly over 100 times without apparent fatigue. If they are immersed in liquid acetone, the actuators are saturated with the solvent and temporarily lose their motility but regain their shape and activity within seconds after the solvent evaporates. The desorption of acetone from the PVDF layer is four times faster than its adsorption, and the actuator composed of a single PVDF layer maintains its ability to move over an acetone-soaked filter paper even after several days. The controllable and reproducible sensing capability of this smart material can be utilized for actuating dynamic elements in soft robotics.
Saccharin is a cyclic sulfimide whose sodium salt, commercially available under the trade name "Sweet’N Low" is one of the most commonly used artificial low-calorie sweeteners, and is also the main sugar substitute in the diabetics’ diet. Being an acid (pKa = 1.6), it is readily deprotonated in solution and affords solid ionic salts or coordination compounds with transition metals where its conjugate base (saccharinate ion) displays a wealth of coordination modes. Here we report the first two examples of ionic cocrystals of molecular saccharin where saccharin exists as a neutral species and an ion in the same crystal. With rubidium and cesium cations, saccharin forms isomorphous solid hemihydrate salts. When saccharin is supplied in excess to the reaction mixture, neutral saccharin molecules are stoichiometrically incorporated in both crystals and stable isomorphous ionic cocrystals are obtained. The formation of ionic cocrystals is unprecedented, and adds a new aspect to the rich crystal chemistry of the artificial sweetener.
An unprecedented tetranuclear gold derivative with unusual gold-enyne moieties is prepared by a mild and neat rearrangement of a dinuclear gold complex with a bridging bis(diphenylphosphino)alkyne and terminal alkynyl ligands. The complex originates as a consequence of an intramolecular addition of the AuCCTol fragment to the internal diphosphine triple bond Ph2PCCPPh2. The crystal structure of the tetranuclear complex shows a dinuclear metallacycle with a very short Au⋯Au bond interaction and bridging phosphino–enyne ligands. This disposition clearly stabilises the elusive vinyl gold species omnipresent as intermediates in gold-catalysed reactions.
In salient effects, still crystals of solids that switch between phases acquire a momentum and are autonomously propelled due to rapid release of elastic energy accrued during a latent structural transition induced by heat, light or mechanical stimulation. Herein we report that when the mechanical reconfiguration is induced by change of temperature in thermosalient crystals, bursts of detectable acoustic waves are generated prior to their self-actuation. The results provide compelling evidence that the thermosalient transitions in organic and organic-containing crystals are molecular analogues of the martensitic transitions in some metals and metal alloys such as steel and shape memory alloys. Within a broader context, the results reveal that akin to metallic bonding, the intermolecular interactions in molecular solids are capable of gradual accrual and sudden release of substantial amount of strain during anisotropic thermal expansion.
The synthesis and characterization of three novel fluorubine derivatives is reported via three to four simple reaction steps with isolatable intermediates. The functional dyes are characterized by their strong absorption peaks in the visible region and high fluorescence quantum yields. A significant and useful feature is that the properties can be tuned over a wide range by changing the pH. Transformation of the dyes into protonated amidinium salts leads to narrower band gaps and drastically lower LUMO energies. Further reduction of the pH results in the doubly protonated species with high electron deficiency and LUMO energies of ‒4.8 eV, bathochromic shifts, and a strong intensity increase of up to ε = 120000 M‒1 cm‒1.
The propensity for adherence to solid surfaces of asphaltenes, a complex solubility class of heteropolycyclic aromatic compounds from the heavy fraction of crude oil, has long been the root-cause of scale deposition and remains an intractable problem in petroleum industry. Despite that the adhesion is essential to understand the process of asphaltene deposition, the relation between the conformation of asphaltene molecules on mineral substrates and its impact on adhesion and mechanical property of the deposits is not completely understood. To rationalize the primary processes in the process of organic scale deposition, here we use atomic force microscopy (AFM) to visualize the morphology of petroleum asphaltenes deposited on model mineral substrates. High imaging contrast was achieved by the differential adhesion of the tip between asphaltenes and the mineral substrate. While asphaltenes form smooth continuous films on all substrates at higher concentrations, they deposit as individual nanoparticles at lower concentrations. The size, shape and spatial distribution of the nanoaggregates are strongly affected by the nature of the substrate; while uniformly distributed spherical particles are formed on highly polar and hydrophilic (mica) substrates, irregular islands and thicker patches are observed with substrates of lower polarity (silica and calcite). Asphaltene nanoparticles flatten when adsorbed on highly oriented pyrolytic graphite due to π—π/ interactions with the polycyclic core. Force-distance profiles provide direct evidence of the conformational changes of asphaltene molecules on hydrophilic/hydrophobic substrates that result in dramatic changes in adhesion and mechanical properties of asphaltene deposits. Such understanding of the nature of adhesion and mechanical properties tuned by surface properties, on the level of asphaltene nanoaggregates, would contribute to the design of efficient asphaltene inhibitors for preventing asphaltene fouling on targeted surfaces. Unlike flat surfaces, the AFM phase contrast images of defected calcite surfaces show that asphaltenes form continuous deposits to fill the recesses, and this process could trigger the onset for asphaltene deposition.
Atomic force microscopy (AFM) was applied to obtain high spatial resolution surface energy distribution in the trans and cis domains on the surface of an azobenzene single crystal. The results demonstrate that AFM-based surface-sensitive techniques can be used to probe dynamic changes in surface properties that occur upon photoinduced isomerization.
Plastic bending of organic crystals is a well-known, yet mechanistically poorly understood phenomenon. On three structurally related epimers, derivatives of galactose, glucose and mannose, it is demonstrated here that small changes in the molecular structure can have a profound effect on the mechanical properties. While the galactose derivative affords crystals which can be easily bent, the crystals of the derivatives of glucose and mannose are brittle and do not bend. Structural, microscopic and mechanical evidence is provided showing that hydrogen bonding of water molecules is the key element for sliding over the slip planes in the crystal and accounts for the plastic bending.
In this work, we used firefly oxyluciferin (OxyLH2) and its polarity-dependent fluorescence as a sensitive tool to monitor biomolecular interactions. The chromophores, OxyLH2 and its two analogues 4-MeOxyLH and 4,6’-DMeOxyL, were modified trough carboxylic functionalization and then coupled to the N-terminus part of Tat and NCp7 peptides of Human Immunodeficiency Virus type-1 (HIV-1). The photophysical properties of the labelled peptides were studied in live cells as well as in complex with different oligonucleotides in solution. By monitoring the emission properties of these derivatives we were able, for the first time, to study in-vitro biomolecular interactions using oxyluciferin as a sensor. In an additional application, cyclopropyl-oxyluciferin (5,5-Cpr-OxyLH) was site-specifically conjugated to the thiol group (Cys 232) of the human protein α-1 antytripsin to investigate its interaction with porcine pancreatic elastase. Our data demonstrate that OxyLH2 and its derivatives can be used as fluorescence reporters for monitoring biomolecular interactions.
Cross-conjugated quinoid betaines 4 (2,5-bis(alkoxycarbonyl)-3,6-dioxo-4-(1-pyridinium-1-yl)cyclohexa-1,4-dien-1-olates; Liebermann betaines) were synthesized from 2,5-dichloro-3,6-dioxo-cyclohexa-1,4-diene-1,4-dicarboxylates (2) and pyridines in acetone containing water. Their structure was secured by NMR spectroscopy and by X-ray diffraction analysis of 4f (alkoxy = OEt, pyridine = 4-Me2NC5H4N). Betaines 4 show comparatively high reactivity towards nucleophiles as a consequence of their cross-conjugated character. Betaine 4a and hydroxy-3,4-methylenedioxybenzene (sesamol) condense to give a pyridinium quinolate salt 14 which has a bifurcate hydrogen bond from a pyridinium N+–H donor to both carbonyl (C=O) and olate (C–O–) acceptors in the solid state. Betaine 4b hydrolyzes in aqueous solution to give diethyl 2,5-dihydroxy-3,6-dioxocyclohexa-1,4-diene-1,4-dicarboxylate (11) as a pyridinium salt, or as polymeric zinc(II) complex of the dianion of 11 in the presence of ZnCl2. Dihydroxyquinone 11 was analytically differentiated from its independently prepared hydroquinone form, diethyl 2,3,5,6-tetrahydroxy-terephthalate (12), by NMR analysis in solution and X-ray crystal structure determination of both compounds.
The range of unit cell orientations generated at the kink of a bent single crystal poses unsurmountable challenges with diffraction analysis and limits the insight into the molecular-scale mechanism of bending. On a plastically bent crystal of hexachlorobenzene it is demonstrated here that spatially resolved microfocus infrared spectroscopy using synchrotron radiation can be applied in conjunction with periodic density functional theory calculations to predict spectral changes or to extract information on structural changes that occur as a consequence of bending. The approach reproduces well the observed trends, such as the wall effects, and provides estimation of the vibrational shifts, unit cell deformations and intramolecular parameters. Generally, expansion of the lattice induces red-shift while compression induces larger blue-shift of the characteristic ν(C—C) and ν(C—Cl) modes. Uniform or non-uniform expansion or contraction of the unit cell of 0.1 Å results in shifts of several cm‒1, whereas deformation of the cell of 0.5o at the unique angle causes shifts of <0.5 cm‒1. Since this approach does not include parameters related to the actual stimulus by which the deformation has been induced, it can be generalized and applied to other mechanically, photochemically or thermally bent crystals.
Phenotype-based screening of diverse compound collections generated by privileged substructure-based diversity-oriented synthesis (pDOS) is considered one of the prominent approaches in the discovery of novel drug leads. However, one key challenge that remains is the development of efficient and modular synthetic routes toward the facile access of privileged small-molecule libraries with skeletal and stereochemical complexity and drug-like properties. In this regard, we describe herein, a novel and diverse one-pot procedure for the diastereoselective synthesis of privileged polycyclic benzopyrans and benzoxepines. These unexplored chemotypes were accessed utilizing an acid-mediated diaza-Diels-Alder reaction of 2-allyloxy- and/or homoallyloxy-benzaldehyde with 2-aminoazine building blocks. Profiling of representative analogs against blood-stage P. falciparum parasites, identified three lead candidates with low micromolar antimalarial activity.