Twisted Conformation Research Articles

Sterically crowded di-indazolyl-pyridines: Iron(II) complexation studies

Abstract 4-(2,6-Di(2H-indazol-2-yl)pyridin-4-yl)benzoic acid (1) and 10-(2,6-di(1H-pyrazol-1-yl)pyridin-4-yl)anthracene-9-carboxylic acid (2) were required for adsorption studies on Ag(111), with a view to subsequent iron(II) complexation and formation of well-ordered spin-responsive self-assembled monolayers. While the generation of these compounds has remained elusive, several intermediates and by-products were obtained, potentially useful as dipyrazolylpyridine-related derivatives and for metal ion coordination. 3,5-Dichloro-2,6-diindazolylpyridine-4-amine, which forms as a mixture of regioisomers, was synthesised, the mixture separated, and the components characterised (3,5-dichloro-2,6-di(2H-indazol-2-yl)pyridin-4-amine; 3,5-dichloro-2-(1H-indazol-1-yl)-6-(2H-indazol-2-yl)pyridin-4-amine; 3,5-dichloro-2,6-di(1H-indazol-1-yl)pyridin-4-amine). Their iron(II) complexes have been prepared and fully characterised, including single crystal X-ray structure determination. The complexes are instructive examples of the influence of ligand design (“steric jamming”) on the spin-crossover (SCO) activity of FeII centres. Bulky substitution, which entails twisted ligand conformation, increases intramolecular crowding. This prevents contraction of the metal coordination sphere, which would be a prerequisite for thermally inducible SCO. Mössbauer spectroscopy has revealed that the complexes remain predominantly high-spin (HS) between 20 and 200 K, and that a mixture of conformational HS isomers is present in the microcrystalline solid.

AIE activity, mechanochromic property and solvent inclusion of two β-diketones with tetraphenylethylene unit

Highly twisted molecular conformation easily leads to the loose molecular packing and big voids, which are desirable for mechanochromism and solvent inclusion. Here, TPE-BF and TPE-BT with highly twisted molecular conformation were designed and synthesized by α-substitution of two β-diketonates. TPE-BF and TPE-BT show similar aggregation-induced emission activity, but different mechanochromism. Subsequently, the corresponding internal mechanism are analyzed and discussed in-depth by XRD, DSC, fluorescence lifetime, crystal analysis and theoretical calculation. Compared with crystal TPE-BF, crystal TPE-BT exhibits more obvious mechanochromism (red shift of 12 nm) before/after grinding, which is attributed to EtOAc inclusion and different intermolecular interactions and stacking. Furthermore, wavelength shifts of TPE-BF and TPE-BT do not exceed 35 nm after phase transition from crystalline state to amorphous state. Obviously, highly twisted molecular conformations fail to bring about high-contrast mechanochromism (wavelength shift above 100 nm), whose reason should be the suppressed intermolecular π-π interactions and overlap before/after grinding. Combined with previous research results of our laboratory, the luminogens forming solvent inclusion generally have twisted molecular conformation, and similar structural fragment with solvent molecule, which will provide a potential design strategy for selective solvent inclusion.

Influence of C28H58 on the structure and phase change of C28H58/C22H46 n-alkane mixtures

This study adopted molecular dynamics to investigate the influence of C28H58 mass fraction on the structure and phase change of C28H58/C22H46 n-alkane mixtures at different temperatures; systematically analyzed the C–H and C–C bond lengths, changes in the H–C–H bond angle and C–C–C–C torsion angle, and energy conversions within the mixture during heating of C28H58/C22H46 n-alkane mixtures; calculated the self-diffusion coefficient (D) by combining the Einstein relation and mean squared displacement; and determined the phase change temperature of each mixture according to the relationship between D and temperature. The results show that, at 280 K, changing the mass fraction of C28H58 does not affect the C–H and C–C bond lengths and the H–C–H bond angle. At 350 K, the C–H bond length decreases with the increase in the mass fraction of C28H58, the C–C bond length increases slightly when the mass fraction is 65.2% and remains unchanged for other mass fractions, and the H–C–H bond angle slightly decreases. With an increase in temperature, the peak intensity of the stretched conformation at ±180° gradually decreases, while the peak of the twisted conformation appears around ±70°, and the degree of twist of the C–C–C–C dihedral angle in the mixture increases. The phase change temperature begins to increase slowly with the increase in the mass fraction of C28H58, and the phase change temperature increases rapidly when the mass fraction exceeds 65.2%. The kinetic and potential energies of the mixture tend to increase with the increasing mass fraction of C28H58.

An Oligomer Approach for Blue Thermally Activated Delayed Fluorescent Emitters Based on Twisted Donor-Acceptor Units.

The development of efficient blue donor-acceptor thermally activated delayed fluorescence (TADF) emitters remains a challenge. To enhance the efficiency of TADF-related processes of the emitter, we targeted a molecular design that would introduce a large number of intermediate triplet states between the lowest energy excited triplet (T1) and singlet (S1) excited states. Here, we introduce an oligomer approach using repetitive donor-acceptor units to gradually increase the number of quasi-degenerate states. In our design, benzonitrile (BN) moieties were selected as acceptors that are connected together via the amine donors, acting as bridges to adjacent BN acceptors. To preserve the photoluminescence emission wavelength across the series, we employed a design based on an ortho substitution pattern of the donors about the BN acceptor that induces a highly twisted conformation of the emitters, limiting the conjugation. Via a systematic photophysical study, we show that increasing the oligomer size allows for enhancement of the intersystem crossing and reverse intersystem crossing rates. We attribute the increasing intersystem crossing rate to the increasing number of intermediate triplet states along the series, confirmed by the time-dependent density functional theory. Overall, we report an approach to enhance the efficiency of TADF-related processes without changing the blue photoluminescence color.

Titelbild: Highly Twisted Conformation Thiopyrylium Photosensitizers for In Vivo Near Infrared‐II Imaging and Rapid Inactivation of Coronavirus (Angew. Chem. 13/2023)

The relationship between molecular configuration and charge transfer processes in near-infrared-II (NIR-II) chromophores was studied, and subsequently instructed the engineering of an efficient NIR photosensitizer (PS), as reported by Wenbo Hu, Yuliang Xiao et al. in their Research Article (e202214875). The resulting NIR-II PS not only enables NIR-II image-guided in vivo pulmonary coronavirus photo-ablation but also demonstrates a facile approach for the development of NIR heavy-atom-free PSs. The relationship between molecular configuration and charge transfer processes in near-infrared-II (NIR-II) chromophores was studied, and subsequently instructed the engineering of an efficient NIR photosensitizer (PS), as reported by Wenbo Hu, Yuliang Xiao et al. in their Research Article (e202214875). The resulting NIR-II PS not only enables NIR-II image-guided in vivo pulmonary coronavirus photo-ablation but also demonstrates a facile approach for the development of NIR heavy-atom-free PSs. Receptors Enzymes Hydrogen-Bonded Organic Frameworks Metallocenes

Cover Picture: Highly Twisted Conformation Thiopyrylium Photosensitizers for In Vivo Near Infrared‐II Imaging and Rapid Inactivation of Coronavirus (Angew. Chem. Int. Ed. 13/2023)

The relationship between molecular configuration and charge transfer processes in near-infrared-II (NIR-II) chromophores was studied, and subsequently instructed the engineering of an efficient NIR photosensitizer (PS), as reported by Wenbo Hu, Yuliang Xiao et al. in their Research Article (e202214875). The resulting NIR-II PS not only enables NIR-II image-guided in vivo pulmonary coronavirus photo-ablation but also demonstrates a facile approach for the development of NIR heavy-atom-free PSs. The relationship between molecular configuration and charge transfer processes in near-infrared-II (NIR-II) chromophores was studied, and subsequently instructed the engineering of an efficient NIR photosensitizer (PS), as reported by Wenbo Hu, Yuliang Xiao et al. in their Research Article (e202214875). The resulting NIR-II PS not only enables NIR-II image-guided in vivo pulmonary coronavirus photo-ablation but also demonstrates a facile approach for the development of NIR heavy-atom-free PSs. Receptors Enzymes Hydrogen-Bonded Organic Frameworks Metallocenes

A Versatile Theranostic Nanoplatform with Aggregation-Induced Emission Properties: Fluorescence Monitoring, Cellular Organelle Targeting, and Image-Guided Photodynamic Therapy.

Photosensitizers (PSs) play a key role in the photodynamic therapy (PDT) of tumors. However, commonly used PSs are prone to intrinsic fluorescence aggregation-caused quenching and photobleaching; this drawback severely limits the clinical application of PDT, necessitating new phototheranostic agents. Herein, a multifunctional theranostic nanoplatform (named TTCBTA NP) is designed and constructed to achieve fluorescence monitoring, lysosome-specific targeting, and image-guided PDT. TTCBTA with a twisted conformation and D-A structure is encapsulated in amphiphilic Pluronic F127 to form nanoparticles (NPs) in ultrapure water. The NPs exhibit biocompatibility, high stability, strong near-infrared emission, and desirable reactive oxygen species (ROSs) production capacity. The TTCBTA NPs also show high-efficiency photo-damage, negligible dark toxicity, excellent fluorescent tracing, and high accumulation in lysosome for tumor cells. Furthermore, TTCBTA NPs are used to obtain fluorescence images with good resolution of MCF-7 tumors in xenografted BALB/c nude mice. Crucially, TTCBTA NPs present a strong tumor ablation ability and image-guided PDT effect by generating abundant ROSs upon laser irradiation. These results demonstrate that the TTCBTA NP theranostic nanoplatform may enable highly efficient near-infrared fluorescence image-guided PDT.

Medium-Ring Strategy Enables Multiple Resonance Emitters with Twisted Geometry and Fast Spin-Flip to Suppress Efficiency Roll-Off.

Suppressing aggregation-caused quenching (ACQ) effect and reducing device efficiency roll-off are both crucial yet challenging for multi-resonance (MR) emitters. Herein, we put forward a medium-ring strategy to design efficient MR emitters that feature heptagonal tribenzo[b,d,f]azepine (TBA) donors. The highly twisted conformation enlarges the intermolecular distances between the MR-emitting cores, and thus suppresses ACQ effect. Meanwhile, the introduction of heptagonal donors enhances spin-orbital coupling, so as to accelerate reverse intersystem crossing (RISC) process. This medium-ring strategy gives rise to the first example of blue MR emitter that simultaneously possesses radiative decay rate as fast as 108 s-1 and RISC rate as fast as 106 s-1 . Accordingly, DTBA-B2N3 enables to assemble high-performance blue organic light-emitting diodes (OLEDs) with maximum external quantum efficiency (EQEmax ) of 30.9 % and alleviated efficiency roll-off (EQE1000 : 20.5 %).

Medium‐Ring Strategy Enables Multiple Resonance Emitters with Twisted Geometry and Fast Spin‐Flip to Suppress Efficiency Roll‐Off

AbstractSuppressing aggregation‐caused quenching (ACQ) effect and reducing device efficiency roll‐off are both crucial yet challenging for multi‐resonance (MR) emitters. Herein, we put forward a medium‐ring strategy to design efficient MR emitters that feature heptagonal tribenzo[b,d,f]azepine (TBA) donors. The highly twisted conformation enlarges the intermolecular distances between the MR‐emitting cores, and thus suppresses ACQ effect. Meanwhile, the introduction of heptagonal donors enhances spin‐orbital coupling, so as to accelerate reverse intersystem crossing (RISC) process. This medium‐ring strategy gives rise to the first example of blue MR emitter that simultaneously possesses radiative decay rate as fast as 108 s−1 and RISC rate as fast as 106 s−1. Accordingly, DTBA‐B2N3 enables to assemble high‐performance blue organic light‐emitting diodes (OLEDs) with maximum external quantum efficiency (EQEmax) of 30.9 % and alleviated efficiency roll‐off (EQE1000: 20.5 %).

AIEgens Based on Dehydroabietic Acid Triarylamine and Tetraphenylethene: Synthesis, Luminescence Regulation, and Application in Cell Imaging

Biomass-derived luminogens with strong emission capacity in the aggregated or solid state are in demand because of their renewability, sustainability, and biocompatibility. Herein, we synthesized aggregation-induced emission luminogens (AIEgens) based on dehydroabietic acid triarylamine (DTPA) derived from natural rosin, and their spectral properties, molecular conformation, electron distribution, and energy levels were explored to elucidate the effect and mechanism of structure regulation. The prepared AIEgens exhibited different emission wavelengths and luminescence efficiencies attributed to the conjugation degree and molecular motion. DTPA–mTPE with a meta-linkage mode exhibits blue emission with highest quantum yield among all compounds. DDPA–pTPE, formed by DTPA sharing a phenyl ring with TPE, redshifts visibly from 488 to 508 nm, attributed to the narrower excited-state energy gap. Introducing a dehydroabietic acid skeleton creates a rigid molecular conformation, and a highly twisted molecular conformation is unfavorable to stabilize the excited-state molecular conformation and reduces luminous efficiency. Finally, DTPA–pTPE, DTPA–mTPE, 2DTPA–mTPE, and DDPA–pTPE were prepared nanoparticles, which exhibited low cellular toxicity and excellent cell imaging results. This work offers new insights into the synthesis of rosin-based AIEgens, facilitating the design of naturally derived luminescent materials.

Photoreaction of indazole metastable-state photoacid

Indazole metastable-state photoacids have been recently applied to modulating local pH of tumor and brain in animal studies. The mechanism of this type of photoacid was previously assumed to be the same as that of the extensively studied merocyanine photoacids. However, this work showed that the photo reaction of indazole photoacid is significantly different from merocyanine photoacid in water. An indazole photoacid with high water solubility up to 70 mM was designed and synthesized. Photoirradiation generates a quinoidal cis-conformer in water instead of the spiro conformer generally expected for a metastable-state photoacid. Although the twisted conformation reduced conjugation between the electron-withdrawing moiety and the acidic moiety, the cis-conformer possesses a higher acidity than that of the trans-conformer due to the unusual quinoidal structure. In organic solvents, the cis-isomer possesses a Kekule structure, which has lower acidity than that of the trans-conformer. In the presence of a weak base, photoirradiation reversibly converted the trans-conformer to the spiroconformer. Experiments showed that deprotonated cis-conformer is the intermediate for both the spiro formation and the reverse cis-to-trans reaction. Addition of an acid stops both reactions and locks the photoproduct to the protonated cis-conformer.

(Z)-4,5-Di-bromo-3,3,6,6-tetra-methyl-2,3,6,7-tetra-hydro-thiepine-1,1-dione.

The crystal of the title compound, C10H16Br2O2S, is formed from layers built from centrosymmetric pairs of mol-ecules. The mol-ecule adopts a twist conformation with the carbon atoms next to sulfur above or below the mean plane.

Coevolution and smFRET Enhances Conformation Sampling and FRET Experimental Design in Tandem PDZ1-2 Proteins.

The structural flexibility of proteins is crucial for their functions. Many experimental and computational approaches can probe protein dynamics across a range of time and length-scales. Integrative approaches synthesize the complementary outputs of these techniques and provide a comprehensive view of the dynamic conformational space of proteins, including the functionally relevant limiting conformational states and transition pathways between them. Here, we introduce an integrative paradigm to model the conformational states of multidomain proteins. As a model system, we use the first two tandem PDZ domains of postsynaptic density protein 95. First, we utilize available sequence information collected from genomic databases to identify potential amino acid interactions in the PDZ1-2 tandem that underlie modeling of the functionally relevant conformations maintained through evolution. This was accomplished through combination of coarse-grained structural modeling with outputs from direct coupling analysis measuring amino acid coevolution, a hybrid approach called SBM+DCA. We recapitulated five distinct, experimentally derived PDZ1-2 tandem conformations. In addition, SBM+DCA unveiled an unidentified, twisted conformation of the PDZ1-2 tandem. Finally, we implemented an integrative framework for the design of single-molecule Förster resonance energy transfer (smFRET) experiments incorporating the outputs of SBM+DCA with simulated FRET observables. This resulting FRET network is designed to mutually resolve the predicted limiting state conformations through global analysis. Using simulated FRET observables, we demonstrate that structural modeling with the newly designed FRET network is expected to outperform a previously used empirical FRET network at resolving all states simultaneously. Integrative approaches to experimental design have the potential to provide a new level of detail in characterizing the evolutionarily conserved conformational landscapes of proteins, and thus new insights into functional relevance of protein dynamics in biological function.

Highly Twisted Conformation Thiopyrylium Photosensitizers for In Vivo Near Infrared-II Imaging and Rapid Inactivation of Coronavirus.

Despite significant effort, a majority of heavy-atom-free photosensitizers have short excitation wavelengths, thereby hampering their biomedical applications. Here, we present a facile approach for developing efficient near-infrared (NIR) heavy-atom-free photosensitizers. Based on a series of thiopyrylium-based NIR-II (1000-1700 nm) dyads, we found that the star dyad HD with a sterically bulky and electron-rich moiety exhibited configuration torsion and significantly enhanced intersystem crossing (ISC) compared to the parent dyad. The electron excitation characteristics of HD changed from local excitation (LE) to charge transfer (CT)-domain, contributing to a ≈6-fold reduction in energy gap (ΔEST ), a ≈10-fold accelerated ISC process, and a ≈31.49-fold elevated reactive oxygen species (ROS) quantum yield. The optimized SP@HD-PEG2K lung-targeting dots enabled real-time NIR-II lung imaging, which precisely guided rapid pulmonary coronavirus inactivation.

Highly Twisted Conformation Thiopyrylium Photosensitizers for In Vivo Near Infrared‐II Imaging and Rapid Inactivation of Coronavirus

AbstractDespite significant effort, a majority of heavy‐atom‐free photosensitizers have short excitation wavelengths, thereby hampering their biomedical applications. Here, we present a facile approach for developing efficient near‐infrared (NIR) heavy‐atom‐free photosensitizers. Based on a series of thiopyrylium‐based NIR‐II (1000–1700 nm) dyads, we found that the star dyad HD with a sterically bulky and electron‐rich moiety exhibited configuration torsion and significantly enhanced intersystem crossing (ISC) compared to the parent dyad. The electron excitation characteristics of HD changed from local excitation (LE) to charge transfer (CT)‐domain, contributing to a ≈6‐fold reduction in energy gap (ΔEST), a ≈10‐fold accelerated ISC process, and a ≈31.49‐fold elevated reactive oxygen species (ROS) quantum yield. The optimized SP@HD‐PEG2K lung‐targeting dots enabled real‐time NIR‐II lung imaging, which precisely guided rapid pulmonary coronavirus inactivation.

Methyl 1-[(6-meth-oxy-5-methyl-pyrimidin-4-yl)meth-yl]-1H-benzo[d]imidazole-7-carboxyl-ate: a combined X-ray and DFT study.

The title compound, C16H16N4O3, was obtained as a side product during the synthesis of the previously reported anti-tubercular agent N-(2-fluoro-eth-yl)-1-[(6-meth-oxy-5-methyl-pyrimidin-4-yl)meth-yl]-1H-benzo[d]imidazole-4-carboxamide and structurally characterized by X-ray crystallography and computational methods. In the crystal (space group P21/n, Z = 4), the title compound adopts a twisted conformation with a dihedral angle between the benzimidazole and pyrimidine mean planes of 84.11 (3)°. The carboxyl-ate group and the 5-methyl group on the pyrimidine ring exhibit partial disorder. The DFT-optimized mol-ecular structure resembles the structure of the minor component in the crystal.

Monoammonium Trimetaphosphimate (NH4)H2(PO2NH)3

Trimetaphosphimates show a rich structural variability in both cation coordination and anion arrangement. They are precursors for crystalline, as well as amorphous oxonitridophosphates. The ammonium trimetaphosphimate (NH4)H2(PO2NH)3 is formed during the decomposition of the corresponding acid in solution. The monoclinic crystal structure of the monoammonium salt was elucidated by single crystal X-ray diffraction using synchrotron radiation. The trimetaphosphimate monoanions exhibit a twist conformation and form crankshaft-like stacks along [100], which have so far only been observed in (NH4)3(PO2NH)3·H2O and Ag3(PO2NH)3. (NH4)H2(PO2NH)3 decomposes at 170 °C, forming a poorly crystalline phase. Therefore, it is a model system and possible precursor for the synthesis of oxonitridophosphates.

Stack bonding in polyaromatic hydrocarbons.

Parallel displacement of π-stacked component molecules enhances the efficiency of organic semiconductors by maximizing interpenetration of the π-densities. Dimers of symmetric polyaromatic hydrocarbons coronene, hexabenzo[bc,de,gh,kl,no,qr]coronene, circumcoronene, kekulene, and circumcircumcoronene are examined using density functional theory from the stack bonding perspective which considers π-stacking interactions in terms of contributions of monomer π-orbital overlap to the character of dimer orbitals. Energetically favored parallel displaced and/or twisted dimer conformations are consistent with patterns of mixing of the monomer molecular orbitals (MOs) that maximize interpenetration of the π densities. The multiple minima found along parallel displacement (PD) coordinates coincide with the formation of dimer MOs formally antibonding between the monomers at the sandwich conformation to bonding at the PD minima. Minima identified with favorable stack bonding are consistent with polymorphs found in large polyaromatic hydrocarbons.

Bis(naphthobipyrrolyl)methene-derived hexapyrrolic BODIPY as a single-molecule helicate with near-infrared emission.

Helically twisted bis(naphthobipyrrolyl)methene-derived open-chain hexapyrroles have been synthesized as HCl salts and the corresponding BODIPY. Their solid-state structures elucidated by single-crystal X-ray diffraction analysis clearly showed the presence of intramolecular hydrogen bonds, which were concluded to play a pivotal role in stabilizing the twisted conformation. Both molecules were observed to be NIR active, with the BODIPY moiety emission extending beyond 800 nm.

Multifunctional Fluorescent Materials with Reversible Mechanochromism and Distinct Photochromism

AbstractIt is extremely significant and desirable to integrate the fascinating mechanochromism and photochromism in one simple molecule. Herein, two intriguing cyanostilbene‐containing triphenylamine (TPA)/tetraphenylethylene (TPE) derivatives (Z‐TPA‐MB and Z‐TPE‐MB) are elaborately designed, which not only display excellent aggregation‐induced emission (AIE) properties with high solid‐state fluorescence quantum yields (60.9% and 63.8%) but also exhibit reversible and high contrast mechanochromism and distinct photochromism. The powders of Z‐TPA‐MB and Z‐TPE‐MB both exhibit large red‐shift under mechanical stimulation based on the highly twisted conformation and the resulting loose packing mode, accompanied by significant changes in apparent and fluorescent colors. Meanwhile, their solid‐state fluorescence can be reversibly switched between crystalline and amorphous structures through alternating grinding and solvent fuming, exhibiting good fatigue resistance. In addition, the molecules also exhibit distinct dual‐mode photochromic behaviors owing to the presence of cyanostilbene moieties: under 420/365 nm light irradiation, the fluorescence of which decreases in solution owing to the photo‐isomerization, while decreases and blue‐shifts in the aggregated state owing to the photodimerization reactions. The reversible, tractable, and high‐contrast mechanochromism and distinct photochromism of the cyanostilbene‐containing molecules endow them with excellent application prospects in the field of rewritable papers and photo‐patterning.