Supermolecular Complexes Research Articles

Squeezing formaldehyde into C60 fullerene

The cavity inside fullerene C60 provides a highly symmetric and inert environment for housing atoms and small molecules. Here we report the encapsulation of formaldehyde inside C60 by molecular surgery, yielding the supermolecular complex CH2O@C60, despite the 4.4 Å van der Waals length of CH2O exceeding the 3.7 Å internal diameter of C60. The presence of CH2O significantly reduces the cage HOMO-LUMO gap. Nuclear spin-spin couplings are observed between the fullerene host and the formaldehyde guest. The rapid spin-lattice relaxation of the formaldehyde 13C nuclei is attributed to a dominant spin-rotation mechanism. Despite being squeezed so tightly, the encapsulated formaldehyde molecules rotate freely about their long axes even at cryogenic temperatures, allowing observation of the ortho-to-para spin isomer conversion by infrared spectroscopy. The particle in a box nature of the system is demonstrated by the observation of two quantised translational modes in the cryogenic THz spectra.

Signals by flow solitons and supermolecular complex by DDMC/PTX in TME

Signals by flow solitons and supermolecular complex by DDMC/PTX in TME

Theoretical terahertz spectroscopy of free radical solutes in solution: an EPR spin probe in water.

Free radical species are used as spin labels in electron paramagnetic resonance (EPR) spectroscopy of biomolecular systems in water, for instance in the frame of Overhauser dynamic nuclear polarization (ODNP) relaxometry to probe the local hydration water dynamics close to protein surfaces in aqueous environments. Widely used in this context are nitroxide spin probes such as TEMPO, PROXYL or MTSL derivatives. Here, we study the THz spectroscopy of HMI (2,2,3,4,5,5-HexaMethylImidazolidin-1-oxyl) in water at ambient conditions which has been recently investigated as to how its EPR properties depend on its solvation pattern in water. To enable theoretical THz spectroscopy of molecular radicals in solution, we have generalized well-established methodologies for THz spectral decomposition of closed-shell systems, namely the supermolecular solvation complex (SSC) and cross-correlation analysis (CCA) techniques, to open-shell polyatomic solute species in water. Based on this methodological advance, we have decomposed and assigned the THz response of HMI including its solvation shell by employing the generalized SSC and CCA methods to cope with the open-shell character of this free radical solute, in particular its unpaired electron localized at the nitroxy group. We reveal that the main modulations of the far-IR spectrum of HMI are dominated by the low-frequency intramolecular modes of the spin probe molecule itself while the solvation of its two hydrogen bonding sites contribute much less intensely in this spectral window. Finally, we have computed THz spectra of HMI with its local solvation water with an aim to provide a theoretical analogue of experimental THz difference spectroscopy. Beyond the specific case, our decomposition methodology that now is able to include open shells can be applied in future work to analyze the low-frequency vibrational response of the solvation shell of other free radicals in solution.

Intermolecular interactions enabled a semiconducting 2D supermolecular complex with robust humidity sensing performance

As essential multifunctional materials, metal-organic complexes are attractive candidates showing superior sensing performance. However, the development of complex-based electronic sensors is still greatly limited by the low conductivity and unsatisfactory properties. Here, we report a new complex with formula of [Cd2(TAA)4(2,2′-bpy)2] (denoted as CdL, HTAA = 3-thiopheneacetic acid, 2,2′-bpy = 2,2′-bipyridine) synthesized via room-temperature precipitation. Hirshfeld surface analysis reveals the important effects of hydrogen bonds (54.6%) and Van der Waals interaction (31.5%) for constructing its 2D supermolecular structure. Favored by these intermolecular interactions, the semiconducting CdL exhibits high electronic conductivity at room temperature (1.71 × 10−5 S/cm). Consequently, the CdL powder was fabricated into a planar impedimetric device with high performance. Particularly, the CdL sensor exhibited high sensitivity (1.2 × 103), fast response (6 s), and small hysteresis (0.92%) in total relative humidity range of 33%−97%. In addition, complex impedance analysis was adopted to clarify the sensing mechanism of CdL. This contribution demonstrates the possible application of low-dimensional complexes in humidity sensors.

Cover Feature: Carrier‐Free Immobilization of Multi‐Enzyme Complex Facilitates In Vitro Synthetic Enzymatic Biosystem for Biomanufacturing (ChemSusChem 6/2023)

The Cover Feature shows the carrier-free immobilization of self-assembled multi-enzyme complexes formed on the basis of polypeptide interactions and enzyme oligomerization. Such supermolecular and water-insoluble enzyme complexes feature a high reaction rate and good recycling capability for the biological multi-enzyme biocatalytic conversion of starch into inositol. The proposed strategy for the carrier-free immobilization of the enzyme complex sheds light on improving the catalytic efficiency of in vitro synthetic enzymatic biosystems. More information can be found in the Research Article by M. Liu et al.

Deficiency of PPP6C protects TNF-induced necroptosis through activation of TAK1

Necroptotic cell death is mediated by a super-molecular complex called necrosome which consists of receptor-interacting protein kinase 1 and 3 (RIPK1, RIPK3) and mixed-lineage kinase domain-like protein (MLKL). The role of these kinases has been extensively investigated in the regulation of necroptosis. However, whether the protein phosphatase is involved in necroptosis is still largely unknown. Here, we identified protein phosphatase 6 catalytic subunit (PPP6C) promotes TNF-induced necroptosis by genome-wide CRISPR/Cas9 library screening. We found that PPP6C deficiency protects cells from TNF-induced necroptosis in a phosphatase-activity-dependent manner. Mechanistically, PPP6C acts as a TGF-β activated kinase 1 (TAK1) phosphatase to inactivate its kinase activity. Deletion of PPP6C leads to hyperactivation of TAK1 and reduced RIPK1 kinase activity upon TNF stimulation. We further showed that heterozygous deletion of Ppp6c in mouse gastrointestinal tract alleviates necroptosis-related tissue injury and inflammation. Thus, our study identifies PPP6C as an important regulator of necroptosis and highlights a central role of phosphatase in the regulation of necroptosis-related diseases.

A hybrid type of chromatic acclimation regulated by the dual green/red photosensory systems in cyanobacteria.

Cyanobacteria are phototrophic bacteria that perform oxygenic photosynthesis. They use a supermolecular light-harvesting antenna complex, the phycobilisome (PBS), to capture and transfer light energy to photosynthetic reaction centers. Certain cyanobacteria alter the absorption maxima and/or overall structure of their PBSs in response to the ambient light wavelength-a process called chromatic acclimation (CA). One of the most well-known CA types is the response to green and red light, which is controlled by either the RcaEFC or CcaSR photosensory system. Here, we characterized a hybrid type of CA in the cyanobacterium Pleurocapsa sp. Pasteur Culture Collection (PCC) 7319 that uses both RcaEFC and CcaSR systems. In vivo spectroscopy suggested that strain PCC 7319 alters the relative composition of green-absorbing phycoerythrin and red-absorbing phycocyanin in the PBS. RNA sequencing and promoter motif analyses suggested that the RcaEFC system induces a gene operon for phycocyanin under red light, whereas the CcaSR system induces a rod-membrane linker gene under green light. Induction of the phycoerythrin genes under green light may be regulated through a yet unidentified photosensory system called the Cgi system. Spectroscopy analyses of the isolated PBSs suggested that hemidiscoidal and rod-shaped PBSs enriched with phycoerythrin were produced under green light, whereas only hemidiscoidal PBSs enriched with phycocyanin were produced under red light. PCC 7319 uses the RcaEFC and CcaSR systems to regulate absorption of green or red light (CA3) and the amount of rod-shaped PBSs (CA1), respectively. Cyanobacteria can thus flexibly combine diverse CA types to acclimate to different light environments.

Preparation of an Acacia-Cysteine Super-Molecular Complex Based on Mechanochemistry and Adsorption Properties for Heavy Metal Removal

Preparation of an Acacia-Cysteine Super-Molecular Complex Based on Mechanochemistry and Adsorption Properties for Heavy Metal Removal

Recent advances in understanding tight junctions

Tight junctions (TJs) are one type of cell–cell junction in epithelial cell types in vertebrates. They form a paracellular diffusion barrier and create the boundary between the apical and basolateral plasma membrane domains. The molecular constituents of TJs have mostly been identified, and now their cell biology has shifted to understanding of their formation, dynamics, and functional regulation as well as their relationship to the organization of epithelial cells. Accumulating novel findings are supported by new methods, including super-resolution microscopy, quantitative microscopy, biophysical measurements, and genome editing-mediated gene manipulation. As a conceptual breakthrough, liquid-liquid phase separation seems to be involved in the formation of TJs as super-molecular complexes. This short article summarizes seminal studies in the cell biology of TJs from the last three years.

Electronic structure and photophysics of a supermolecular iron complex having a long MLCT-state lifetime and panchromatic absorption

Exploiting earth-abundant iron-based metal complexes as high-performance photosensitizers demands long-lived electronically excited metal-to-ligand charge-transfer (MLCT) states, but these species suffer typically from femtosecond timescale charge-transfer (CT)-state quenching by low-lying nonreactive metal-centered (MC) states. Here, we engineer supermolecular Fe(II) chromophores based on the bis(tridentate-ligand)metal(II)-ethyne-(porphinato)zinc(II) conjugated framework, previously shown to give rise to highly delocalized low-lying 3MLCT states for other Group VIII metal (Ru, Os) complexes. Electronic spectral, potentiometric, and ultrafast pump-probe transient dynamical data demonstrate that a combination of a strong σ-donating tridentate ligand and a (porphinato)zinc(II) moiety with low-lying π*-energy levels, sufficiently destabilize MC states and stabilize supermolecular MLCT states to realize Fe(II) complexes that express 3MLCT state photophysics reminiscent of their heavy-metal analogs. The resulting Fe(II) chromophore archetype, FeNHCPZn, features a highly polarized CT state having a profoundly extended 3MLCT lifetime (160 ps), 3MLCT phosphorescence, and ambient environment stability. Density functional and domain-based local pair natural orbital coupled cluster [DLPNO-CCSD(T)] theory reveal triplet-state wavefunction spatial distributions consistent with electronic spectroscopic and excited-state dynamical data, further underscoring the dramatic Fe metal-to-extended ligand CT character of electronically excited FeNHCPZn. This design further prompts intense panchromatic absorptivity via redistributing high-energy absorptive oscillator strength throughout the visible spectral domain, while maintaining a substantial excited-state oxidation potential for wide-ranging photochemistry--highlighted by the ability of FeNHCPZn to photoinject charges into a SnO2/FTO electrode in a dye-sensitized solar cell (DSSC) architecture. Concepts enumerated herein afford opportunities for replacing traditional rare-metal-based emitters for solar-energy conversion and photoluminescence applications.

CK1α, CK1δ, and CK1ε are necrosome components which phosphorylate serine 227 of human RIPK3 to activate necroptosis

Necroptosis is a regulated necrotic cell death pathway, mediated by a supermolecular complex called the necrosome, which contains receptor-interacting protein kinase 1 and 3 (RIPK1, RIPK3) and mixed-lineage kinase domain-like protein (MLKL). Phosphorylation of human RIPK3 at serine 227 (S227) has been shown to be required for downstream MLKL binding and necroptosis progression. Tandem immunoprecipitation of RIPK3 reveals that casein kinase 1 (CK1) family proteins associate with the necrosome upon necroptosis induction, and this interaction depends on the kinase activity of RIPK3. In addition, CK1 proteins colocalize with RIPK3 puncta during necroptosis. Importantly, CK1 proteins directly phosphorylate RIPK3 at S227 in vitro and in vivo. Loss of CK1 proteins abolishes S227 phosphorylation and blocks necroptosis. Furthermore, a RIPK3 mutant with mutations in the CK1 recognition motif fails to be phosphorylated at S227, does not bind or phosphorylate MLKL, and is unable to activate necroptosis. These results strongly suggest that CK1 proteins are necrosome components which are responsible for RIPK3-S227 phosphorylation.

Hydrogels Consisting of Vesicles Constructed via the Self-Assembly of a Supermolecular Complex Formed from α-Cyclodextrin and Perfluorononanoic Acid.

The self-assembly of α-cyclodextrin (α-CD) mixed with a fluorocarbon surfactant, perfluorononanoic acid (PFNA), in aqueous solution was studied. Interestingly, the 1:1 inclusion complex, PFNA@α-CD, was verified to form by 1H nuclear magnetic resonance measurement. Also as the building block, the PFNA@α-CD complex was further self-assembled into worm-like micelles under lower concentrations while hydrogels were self-assembled under higher concentrations. The hydrogels were composed of unilamellar vesicles with polydisperse size, which were clearly detected by freeze-fracture transmission electron microscopy measurements. Besides, the vesicle hydrogels showed high viscoelasticities and a substantial elastic characteristic. Also as revealed by the results of Fourier transform infrared measurements, the driving force for the vesicle and worm-like micelle formation was the hydrogen bonding between α-CD molecules. Then, these vesicles were densely packed to form hydrogels. As far as we know, the self-assembly of CDs and fluorocarbon surfactants based on host-guest inclusion in aqueous solution has been limitedly reported. Our work successfully constructed hydrogels consisting of vesicles through the self-assembly of the α-CD/PFNA complex for the first time and will also provide a better understanding and enrich the fundamental research of the self-assembly behavior of the CD/fluorosurfactant complex.

Maltosyl-β-cyclodextrin mediated SupramolecularHost-Guest inclusion complex used for enhancing baicalin antioxidant activity and bioavailability

Baicalin (BCL) is a flavonoid compound with demonstrated potential therapeutic benefits, but the clinical advancements are limited mainly due to its poor aqueous solubility. A guest-host supermolecular inclusion complex of mono-6-O-α-maltosyl-β-cyclodextrin (G2-β-CD) with BCL was developed to improve the aqueous solubility of BCL. The resultant inclusion complex was characterized by DSC, FT-IR, P-XRD, 1HNMR, 2D-ROESY and SEM analysis. Solubility test suggested that G2-β-CD markedly improved the solubility of BCL and showed AL type phase diagrams. The spectral shifts suggested that the phenyl moiety is buried deeper than the chromen moiety and protrudes from the 6-hydroxyl side of G2-β-CD. Molecular docking verified the experimental findings and supported the insertion of benzene ring of BCL into G2-β-CD cavity via hydrophobic interactions and possible hydrogen bonds. The enhanced bioavailability of the inclusion complex was reflected in earlier Tmax, higher Cmax and larger AUC0-∞ than that of BCL after its oral administration. Taken together, these findings suggested that the solid inclusion complex BCL-G2-β-CD may serve as valuable BCL solid dosage form with good solubility and dissolution rate.

Diverse Chromatic Acclimation Processes Regulating Phycoerythrocyanin and Rod-Shaped Phycobilisome in Cyanobacteria

Cyanobacteria have evolved various photoacclimation processes to perform oxygenic photosynthesis under different light environments. Chromatic acclimation (CA) is a widely recognized and ecologically important type of photoacclimation, whereby cyanobacteria alter the absorbing light colors of a supermolecular antenna complex called the phycobilisome. To date, several CA variants that regulate the green-absorbing phycoerythrin (PE) and/or the red-absorbing phycocyanin (PC) within the hemi-discoidal form of phycobilisome have been characterized. In this study, we identified a unique CA regulatory gene cluster encoding yellow–green-absorbing phycoerythrocyanin (PEC) and a rod-membrane linker protein (CpcL) for the rod-shaped form of phycobilisome. Using the cyanobacterium Leptolyngbya sp. PCC 6406, we revealed novel CA variants regulating PEC (CA7) and the rod-shaped phycobilisome (CA0), which maximize yellow–green light-harvesting capacity and balance the excitation of photosystems, respectively. Analysis of the distribution of CA gene clusters in 445 cyanobacteria genomes revealed eight CA variants responding to green and red light, which are classified based on the presence of PEC, PE, cpcL, and CA photosensor genes. Phylogenetic analysis further suggested that the emergence of CA7 was a single event and preceded that of heterocystous strains, whereas the acquisition of CA0 occurred multiple times. Taken together, these results offer novel insights into the diversity and evolution of the complex cyanobacterial photoacclimation mechanisms.

Self-assembled mechanism of hydrophobic amino acids and β-cyclodextrin based on experimental and computational methods

The β-cyclodextrin (β-CD) can be used to remove bitter taste of protein hydrolysates, which is attributed to its interaction with hydrophobic amino acids included within peptides. But the corresponding mechanism has not been fully clarified. Herein, we systematically investigate the interaction between β-CD and three hydrophobic amino acids involving tryptophan (Trp), tyrosine (Tyr), and phenylalanine (Phe). We prove the formation of amino acid/β-CD supermolecular complexes determined by FS, UV, IR, DSC and NMR, manifesting that no new chemical bond is formed in these complexes. The theoretical interaction conformations are given by molecule docking and further supported by ONIOM (our Own N-layer Integrated Orbital molecular Mechanics) calculations, with the consideration of structural assignments, binding orientations, solvent effects, interaction energies and main forces to form these complexes. Molecular docking results suggest that the hydrophobic amino acids prefer to interact with β-CD by their aromatic ring, meaning hydrophobic interactions are main forces for them entering into the cavity of β-CD. ONIOM-based calculations provide a number of quantum-chemical parameters to confirm our experimental results; meanwhile, to demonstrate that H-bonds play an important role in maintaining the stability of three amino acid/β-CD complexes. This work is help for demonstrating the interaction mechanism of amino acid/β-CD supermolecular system, and guiding how to remove bitterness or undesirable taste of bioactive peptides, even other interested molecules.

Phase 1/2 trial evaluating intratumoral administration of INT230-6 alone and in combination with an anti-PD1 antibody for advanced malignancies.

TPS2609Background: INT230-6 is a supermolecular complex of cisplatin, vinblastine, and an amphiphilic penetration enhancer, formulated for intratumoral injection. This agent utilizes technology tha...

Versatile Supermolecular Inclusion Complex Based on Host-Guest Interaction for Targeted Gene Delivery.

A facile and targeted gene delivery system was prepared by conjugating β-cyclodextrin modified polyethylenimine (PEI-CD) and adamantyl peptide (AdGRGDS) based on host-guest interaction. With the rational design between PEI-CD and AdGRGDS, the PEI-CD/AdGRGDS gene delivery system showed excellent DNA binding capability and exhibited good ability to compact DNA into uniform spherical nanoparticles. In vitro luciferase assay showed that gene expression transfected by PEI-CD/AdGRGDS was stronger than that by PEI-CD in HeLa cells, whereas gene expression transfected by PEI-CD/AdGRGDS and PEI-CD was similar to each other in COS7 cells. Internalization of complexes was qualitatively studied using a confocal laser scanning microscope (CLSM) and quantitatively analyzed by flow cytometry, respectively, and targeting specificity was also evaluated by CLSM. Results of CLSM and flow cytometry indicated that PEI-CD/AdGRGDS had good targeting specificity to tumor cells with integrin αvβ3 overexpression. To further evaluate the targeting specificity and transfection efficiency in vivo, a rat model with murine hepatic carcinoma cell line H22 was used. PEI-CD/AdGRGDS showed stronger gene expression efficiency than PEI-CD via in vivo transfection of pORF-LacZ and pGL-3 plasmids after subcutaneous injection. Interestingly, PEI-CD/AdGRGDS also showed high targeting specificity and transfection distribution to tumor xenograft after tail-vein injection. In vitro and in vivo assays highlighted the importance of GRGDS targeting specificity to tumor cells with integrin αvβ3 overexpression and demonstrated that the PEI-CD/AdGRGDS gene delivery system would have great potential for targeted tumor therapy.

Efficient whole-cell-catalyzing cellulose saccharification using engineered Clostridium thermocellum

BackgroundCost-efficient saccharification is one of the main bottlenecks for industrial lignocellulose conversion. Clostridium thermocellum naturally degrades lignocellulose efficiently using the cellulosome, a multiprotein supermolecular complex, and thus can be potentially used as a low-cost catalyst for lignocellulose saccharification. The industrial use of C. thermocellum is restrained due largely to the inhibition of the hydrolysate cellobiose to its cellulosome. Although the supplementation of beta-glucosidase may solve the problem, the production of the enzymes greatly complicates the process and may also increase the cost of saccharification.ResultsTo conquer the feedback inhibition and establish an efficient whole-cell catalyst for highly efficient cellulose saccharification, we constructed a recombinant strain of C. thermocellum ∆pyrF::CaBglA which produced a secretory exoglucanase CelS-bearing heterologous BGL using a newly developed seamless genome editing system. Without the extra addition of enzymes, the relative saccharification level of ∆pyrF::CaBglA was stimulated by over twofolds compared to its parent strain ∆pyrF through a two-stage saccharification process with 100 g/L Avicel as the carbon source. The production of reducing sugars and the relative saccharification level were further enhanced to 490 mM and 79.4%, respectively, with increased cell density.ConclusionsThe high cellulose-degrading ability and sugar productivity suggested that the whole-cell-catalysis strategy for cellulose saccharification is promising, and the C. thermocellum strain ∆pyrF::CaBglA could be potentially used as an efficient whole-cell catalyst for industrial cellulose saccharification.

CesA protein is included in the terminal complex of Acetobacter

Cellulose is a major biopolymer on the earth that is produced by cellulose synthase in the cell membrane of living organisms. Cellulose synthase is a hetero-subunit complex composed of several different protein subunits, and is visualized as a supermolecular complex called a “terminal complex” by electron microscopy. Such supermolecular organization of an enzyme complex is believed to be important for the fiber formation or crystallization of cellulose microfibrils in cellulose biosynthesis. In the case of the cellulose-producing bacterium Acetobacter, it is hypothesized that the enzyme complex includes at least six subunits given its genetic constitution. However, to date, only three of these molecules have been experimentally confirmed as the subunits included in the terminal complex: CesB, CesD, and ccp2. In this study, we used fluorescence immuno-microscopy to show that CesA protein, the catalytic subunit, is included in the terminal complex of Acetobacter. Furthermore we discuss the obtained microscopic data for improving our understanding of the molecular organization of the bacterial cellulose synthase complex.

Two multifunctional organic-inorganic hybrid complexes based on polyoxometalates, BiEDTA and sodium linker: crystal structures, photochromic, and catalytic performances

Two 3-D organic–inorganic hybrid supermolecular complexes, Na(BiHEDTA·2H2O)3(PW12O40)·2H3O (BiPW) and Na(BiHEDTA·2H2O)3(PMo12O40)·2H3O·2H2O (BiPMo) ethylenediamine tetraacetic acid (EDTA) have been synthesized by solution method and characterized by ultraviolet visible (UV–vis) spectroscopy, thermogravimetric-differential thermal analysis, photoluminescence, cyclic voltammetry, and single-crystal X-ray diffraction (XRD). XRD analysis reveals that BiPW and BiPMo are isostructural with 3-D architectures assembled by 2-D layer tetranuclear cation and a Keggin-type polyoxoanion. Although these two hybrids exhibit similar structures, the properties depend on the nature of polyoxoanion [PM12O40]3− (M = W, Mo). Under UV irradiation, BiPW and BiPMo show fast response of reversible and irreversible photochromism, respectively. BiPW exhibits excellent photocatalytic activity in degradation of methyl orange dyes under irradiation of UV–visible light. It can be reused for at least six cycles without obvious loss of activity in the degradation experiments; BiPMo shows catalytic activity in elimination of methanol. The elimination rate of methanol reaches 56.9% when the concentration of methanol is 2.3 g·m−3 and the flow velocity is 10 mL·min−1 at 100 °C.