Crystallographic Studies Research Articles

Development of Automotive and Marine Appliable Aluminium Composite by Utilizing Agro-Waste Material as Performance Enhancement Particles

Aluminium-based materials are lightweight materials used for producing automotive and aircraft components. However, aluminium materials diminish in performance on exposure to degrading environments, which limits their areas of usage and applications. The degrading effect results in poor resistance to wear and corrosion, reduced properties and defective microstructure. In this work, 6063 aluminium alloy was reinforced with particles of agricultural waste (walnut shell) to produce six samples with five samples of reinforced and a control (unreinforced) sample. Each of the samples of the reinforced alloy was moulded into a 25 mm diameter by 130 mm height using the stir casting method using an industrial pit furnace. The samples were thereafter machined to a diameter of 20 mm and cut into a thickness of 10 mm for characterizations. The potentiodynamic polarization method was used to test for the samples’ corrosion resistance properties following the ASTM G102 standard in 3.65% NaCl test medium. The hardness property was investigated using the Brinell hardness machine following the ASTM A-370 standard, while the microstructure and crystallographic phase studies were carried out using SEM/EDS and XRD profiles, respectively. The unreinforced 6063 Al alloy sample exhibited the highest corrosion rate (Cr) of 0.7321 mm/year and the lowest hardness of 104.94 kgf/mm2. The 10% wt. walnut shell particles (WSP) reinforced 6063 Al alloy sample exhibited the lowest corrosion rate (Cr) of 0.1336 mm/year and the highest hardness of 109.24 kgf/mm2. This indicated that the walnut shell particles enhanced the corrosion and indentation resistance of the alloy. In addition, the SEM images indicated that the agricultural waste (walnut shell particles) reinforced samples exhibited more refined microstructure, lower porosity and smoother morphology compared to the unreinforced (control) sample. Also, the XRD profile of samples revealed some high peak intensity crystallites such as Al(ZnS), Al2O3 and (FeMn)SiO2. These high peak intensity crystallites indicated that these reinforced samples possessed chemical and microstructural homogeneity, high stability and good surface texture.

Magnesium 4, 5, and 6 coordinate complexes with ligands bound via sp or sp2 hybridized atoms

As a metallic element of high natural abundance, magnesium finds a wide range of uses in both stoichiometric and more recently catalytic applications. This often takes advantage of the basic or nucleophilic properties of its compounds or their ability to co-complex with other organometallic compounds. However, the homoleptic chemistry of Mg(II) is heavily skewed towards alkyl and aryl ligands bound via sp2 and sp3 hybridized atoms. Here, we report our combined NMR spectroscopic and X-ray crystallographic study into much rarer alternative THF solvates of homoleptic magnesium complexes using ligands which bind via sp (alkynyl) and sp2 (imido) atoms. Specifically, we exploit the high acidity of terminal alkynes and diphenylacetonitrile to prepare tetra-solvated distorted octahedral complexes Mg(CCC6H4R-p)2(THF)4 (R = Me, CF3) and Mg(NCCPh2)2(THF)4 starting from the commercial alkyl reagent MgBu2. Adopting a similar deprotonative strategy using benzophenoneimine Ph2CNH affords the heteroleptic trinuclear complex Mg3(NCPh2)4nBu2(THF)2 with distorted tetrahedral Mg centres. Related imidomagnesium halide complexes can be accessed either by deprotonation of the imine with a Grignard reagent, or nucleophilic addition of a Grignard reagent to a nitrile, but these unusual five-coordinate complexes are unresponsive to a 1,4-dioxane induced Schlenk equilibrium shift. Employing a higher reflux temperature switching from a THF to a toluene medium permits access to the THF solvate of a homoleptic imido complex which also possesses a trinuclear constitution in Mg3(NCPh2)6(THF)2.

A new organic–inorganic chloride (H3N–(CH2)6–NH3)[SnCl6]: Crystal structure, thermal analysis, vibrational study, and electrical properties

In this work, a new Organic-Inorganic chloride (H3N–(CH2)6-NH3)[SnCl6] (1) has been synthesized and characterized by single crystal X-ray diffraction (XRD), IR, Raman and impedance spectroscopies. The crystallographic study displays that the title compound crystallizes in the triclinic system with the P−1 space group. The vibrational study (IR, Raman) at room temperature confirmed the existence of the organic and inorganic functional groups. Differential scanning calorimetry (DSC) analysis reveals the existence of three reversible phase transitions at T1 = 345/325 K, T2 = 483/443 K, and T3 = 496/465 K (Heating/Cooling). Furthermore, the conductivity analysis and the dielectric properties confirm the presence of these phase transitions. AC-conductivity measurement of (1) has been investigated using complex impedance spectroscopy in frequency and temperature range 10 Hz–5 MHz and 313–523 K, respectively. The study of Nyquist plots showed the contribution of grains and grain boundaries in the electrical study, confirming the existence of a non-Debye type relaxation. The AC conductivity shows that the material has the potential of impedance sensors.

Crystallographic Study of Transformation Products of Heat-Affected Zone and Correlation with Properties of FH690 Heavy-Gauge Marine Steel by Multi-Pass Submerged Arc Welding

In this work, the microstructure–property relationship of the heat-affected zone (HAZ) of a FH690 ultra-heavy marine steel plate was investigated based on insight of microstructure and crystallographic features. After multi-pass welding with a heat input of ~30 kJ/cm, an ~8 mm wide HAZ was obtained with a coarse grain HAZ (CGHAZ) of ~3.8 mm, fine grain HAZ (FGHAZ) of ~3.4 mm, and intercritical HAZ (ICHAZ) of ~1 mm. High impact toughness values of ~120 and 140 J at -60 °C were obtained for coarse grain HAZ and fine grain HAZ, respectively. The microstructure of the CGHAZ and FGHAZ was fine lath bainite. Although the average prior austenite grain size for the CGHAZ was ~75 μm, which was five times that of the FGHAZ (15 μm), a high density of high-angle grain boundaries (HAGBs) with misorientation higher than 45° was obtained in the CGHAZ. This is the underlying reason for the excellent low-temperature toughness of the HAZ. Thermo-dynamic calculations indicated that the high density of HAGBs in the CGHAZ was attributed to the decreased bainitic transformation temperature due to the reduced phase transformation driving force via the high nickel addition, leading to weak variant selection. In addition, the high nickel addition offered high hardenability for high hardness in the FGHAZ. The outcome of this study could provide an experimental and fundamental basis for designing high-strength ultra-heavy steel plates with excellent weldability.

Lasamide, a Potent Human Carbonic Anhydrase Inhibitor from the Market: Inhibition Profiling and Crystallographic Studies.

Lasamide is a synthetic precursor and a contaminant of the diuretic Furosemide manufacturing process and represents a highly valuable building block for fragment-based drug discovery approaches. We assessed the ability of Lasamide to inhibit in vitro the human-expressed Carbonic Anhydrases by means of the stopped-flow technique, and we assessed its binding modes within hCAs II and XII-mimic catalytic clefts by X-ray crystallography. Interestingly, an unprecedented crystal form for the hCA IX mimic H-tag is reported and discussed herein.

Chitosan/La catalyzed synthesis of novel ferrocenated spiropyrrolizidines: Green synthesis, crystallographic, DFT and Hirshfeld surface studies

A novel polymeric catalytic system, utilizing chitosan-bounded lanthanum (chitosan/La), facilitated the formation of spiropyrrolizidine hybrids in higher yield. These hybrids were synthesized via one-pot three component 1,3-dipolar cycloaddition reaction involving ferrocenated chalcones, and azomethine ylides. The chemical structures were elucidated using various spectroscopic techniques and further confirmed via X-ray crystallography of a compound 3. Density functional theory (DFT) calculations executed followed by Gaussian 09 and GaussView 5.0 software provided insights into the optimal structure of molecular compounds. The computational analysis employed the 6–311G++ (d,p) higher-order basis set and the B3LYP method. Additionally, Hirshfeld surface analysis was utilized to predict crystallographic shapes, revealing van der Waals interaction contributing to crystal stabilization.

Exploiting the bile acid binding protein as transporter of a Cholic Acid/Mirin bioconjugate for potential applications in liver cancer therapy.

Bioconjugation is one of the most promising strategies to improve drug delivery, especially in cancer therapy. Biomolecules such as bile acids (BAs) have been intensively explored as carriers, due to their peculiar physicochemical properties and biocompatibility. BAs trafficking is regulated by intracellular lipid-binding proteins and their transport in the liver can be studied using chicken liver Bile Acid-Binding Proteins (cL-BABPs) as a reference model. Therefore, we conceived the idea of developing a BA-conjugate with Mirin, an exonuclease inhibitor of Mre11 endowed with different anticancer activities, to direct its transport to the liver. Following computational analysis of various BAs in complex with cL-BABP, we identified cholic acid (CA) as the most promising candidate as carrier, leading to the synthesis of a novel bioconjugate named CA-M11. As predicted by computational data and confirmed by X-ray crystallographic studies, CA-M11 was able to accommodate into the binding pocket of BABP. Hence, it can enter BAs trafficking in the hepatic compartment and here release Mirin. The effect of CA-M11, evaluated in combination with varying concentrations of Doxorubicin on HepG2 cell line, demonstrated a significant increase in cell mortality compared to the use of the cytotoxic drug or Mirin alone, thus highlighting chemo-sensitizing properties. The promising results regarding plasma stability for CA-M11 validate its potential as a valuable agent or adjuvant for hepatic cancer therapy.

Surface Chemistry Regulation in Cu4I4-Triazolate Metal-Organic Frameworks for One-Step C3H6 Purification from Quaternary C3 Mixtures.

C3H6 is a crucial building block for many chemicals, yet separating it from other C3 hydrocarbons presents a significant challenge. Herein, we report a hydrolytically stable Cu4I4-triazolate metal-organic framework (MOF) (JNU-9-CH3) featuring 1D channels decorated with readily accessible iodine and nitrogen atoms from Cu4I4 clusters and triazolate linkers, respectively. The exposed iodine and nitrogen atoms allow for cooperative binding of C3 hydrocarbons, as evidenced by in situ single-crystal crystallography and Raman spectroscopy studies. As a result, JNU-9-CH3 exhibits substantially stronger binding affinity for C3H4, CH2═C═CH2, and C3H8 than that for C3H6. Breakthrough experiments confirm its ability to directly separate C3H6 (≥99.99%) from C3H4/CH2═C═CH2/C3H8/C3H6 mixtures at varying ratios and flow rates. Overall, we illustrate the cooperative binding of C3 hydrocarbons in a Cu4I4-triazolate MOF and its highly efficient C3H6 purification from quaternary C3 mixtures. The study highlights the potential of MOF adsorbents with metal-iodide clusters for cooperative bindings and hydrocarbon separations.

Miniaturized Modular Click Chemistry-enabled Rapid Discovery of Unique SARS-CoV-2 Mpro Inhibitors With Robust Potency and Drug-like Profile.

The COVID-19 pandemic has required an expeditious advancement of innovative antiviral drugs. In this study, focused compound libraries are synthesized in 96- well plates utilizing modular click chemistry to rapidly discover potent inhibitors targeting the main protease (Mpro) of SARS-CoV-2. Subsequent direct biological screening identifies novel 1,2,3-triazole derivatives as robust Mpro inhibitors with high anti-SARS-CoV-2 activity. Notably, C5N17B demonstrates sub-micromolar Mpro inhibitory potency (IC50 = 0.12 µM) and excellent antiviral activity in Calu-3 cells determined in an immunofluorescence-based antiviral assay (EC50 = 0.078 µM, no cytotoxicity: CC50 > 100 µM). C5N17B shows superior potency to nirmatrelvir (EC50 = 1.95 µM) and similar efficacy to ensitrelvir (EC50 = 0.11 µM). Importantly, this compound displays high antiviral activities against several SARS-CoV-2 variants (Gamma, Delta, and Omicron, EC50 = 0.13 - 0.26 µM) and HCoV-OC43, indicating its broad-spectrum antiviral activity. It is worthy that C5N17B retains antiviral activity against nirmatrelvir-resistant strains with T21I/E166V and L50F/E166V mutations in Mpro (EC50 = 0.26 and 0.15 µM, respectively). Furthermore, C5N17B displays favorable pharmacokinetic properties. Crystallography studies reveal a unique, non-covalent multi-site binding mode. In conclusion, these findings substantiate the potential of C5N17B as an up-and-coming drug candidate targeting SARS-CoV-2 Mpro for clinical therapy.

Biochemical and crystallographic studies of l,d-transpeptidase 2 from Mycobacterium tuberculosis with its natural monomer substrate

The essential l,d-transpeptidase of Mycobacterium tuberculosis (LdtMt2) catalyses the formation of 3→\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ o$$\\end{document}3 cross-links in cell wall peptidoglycan and is a target for development of antituberculosis therapeutics. Efforts to inhibit LdtMt2 have been hampered by lack of knowledge of how it binds its substrate. To address this gap, we optimised the isolation of natural disaccharide tetrapeptide monomers from the Corynebacterium jeikeium bacterial cell wall through overproduction of the peptidoglycan sacculus. The tetrapeptides were used in binding / turnover assays and biophysical studies on LdtMt2. We determined a crystal structure of wild-type LdtMt2 reacted with its natural substrate, the tetrapeptide monomer of the peptidoglycan layer. This structure shows formation of a thioester linking the catalytic cysteine and the donor substrate, reflecting an intermediate in the transpeptidase reaction; it informs on the mode of entrance of the donor substrate into the LdtMt2 active site. The results will be useful in design of LdtMt2 inhibitors, including those based on substrate binding interactions, a strategy successfully employed for other nucleophilic cysteine enzymes.

Characterization of a Lewis adduct in its inner and outer forms.

The entrance channel of bimolecular reactions sometimes involves the formation of outer complexes as weakly bound, fleeting intermediates. Here, we characterize such an outer complex in a system that models the bimolecular, C-O bond-forming reaction of a phosphine oxide Lewis base with a carbenium Lewis acid. Crystallographic studies show that the C-O distance in the outer form exceeds that of the final or inner adduct by 1.1 angstroms. As the system samples the two forms of the complex, which correspond to minima on the corresponding potential energy surface, the C-O linkage switches from a secondary interaction in the outer complex to a dative bond in the inner complex. This phenomenon is harnessed as a functional feature to stabilize xanthylium-based photoredox catalysts.

Protein expression, purification, crystallization and crystallographic studies of BPSL0741 from Burkholderia pseudomallei.

Burkholderia pseudomallei is the causative agent of the lethal disease melioidosis. This bacterium infects animals and humans and is increasingly resistant to multiple antibiotics. Recently, genes associated with survival of the bacterium in the infected host have been identified. One of these genes, bpsl0741, is annotated as a hypothetical protein of 185 amino acids. Here, recombinant BPSL0741 (rBPSL0741) protein was expressed, purified, verified by mass spectrometry, crystallized and analyzed by X-ray diffraction. rBPSL0741 was crystallized by vapor diffusion using a reservoir solution consisting of 0.2 M ammonium acetate, 0.1 M sodium acetate trihydrate pH 4.6, 30% PEG 4000. The crystals diffracted to 2.1 Å resolution using an in-house X-ray diffractometer and belonged to an orthorhombic space group, with unit-cell parameters a = 62.92, b = 64.57, c=89.16 Å. The Matthews coefficient (VM) was calculated to be 2.18 Å3 Da-1, suggesting the presence of two molecules per asymmetric unit and an estimated solvent content of 43.5%. The crystal was deemed to be suitable for further structural studies, which are currently ongoing.

Transition Metal Complexes with Appended Benzimidazole Groups for Sensing Dihydrogenphosphate.

Four new complexes [Ru(bpy)2(bbib)](PF6)2, [Ru(phen)2(bbib)](PF6)2, [Re(CO)3(bbib)(py)](PF6) and [Ir(ppy)2(bbib)](PF6) [where bbib=4,4'-bis(benzimidazol-2-yl)-2,2'-bipyridine] have been prepared and their photophysical properties determined. Their behaviour has been studied with a variety of anions in acetonitrile, DMSO and 10 % aquated DMSO. Acetate and dihydrogenphosphate demonstrate a redshift in the bbib ligand associated absorptions suggesting that the ligand is strongly interacting with these anions. The 3MLCT emissive state is sensitive to the introduction of small quantities of anion (sub-stoichiometric quantities) and significant quenching is typically observed with acetate, although this is less pronounced in the presence of water. The emissive behaviour with dihydrogenphosphate is variable, showing systematic changes as anion concentration increases with several distinct interactions evident. 1H- and 31P-NMR titrations in a 10 % D2O-DMSO-D6 mixture suggest that with dihydrogenphosphate, the imidazole group is able to act as both a proton acceptor and donor. It appears that all four complexes can form a {[complex]2-H2PO4} "dimer", a one-to-one species (which the X-ray crystallography study suggests is dimeric in the solid-state), and a complex with a combined bis(dihydrogenphosphate) complex anion. The speciation relies on complex equilibria dependent on several factors including the complex charge, the hydrophobicity of the associated ligands, and the solvent.

Structural Basis of Main Proteases of Coronavirus Bound to Bofutrelvir

Globally, the continuous spread and evolution of SARS-CoV-2, along with its variants, profoundly impact human well-being, health, security, and the growth of socio-economic. In the field of development of drugs against COVID-19, the main protease (Mpro) is a critical target as it plays a core role in the lifecycle of SARS-CoV-2. Bofutrelvir acts as a potent inhibitor of SARS-CoV-2 Mpro, demonstrating high efficacy and broad-spectrum antiviral activity. Compared to therapies that require pharmacokinetic boosters, such as ritonavir, the monotherapy approach of Bofutrelvir reduces the risk of potential drug interactions, making it suitable for a wider patient population. However, further studies on the potency and mechanism of inhibition of Bofutrelvir against the Mpro of COVID-19 and its variants, together with other coronaviruses, are needed to prepare for the possibility of a possible re-emerging threat from an analogous virus in the future. Here, we reveal the effective inhibition of Bofutrelvir against the Mpro of SARS-CoV-2, SARS-CoV, and HCoV-229E through FRET and crystallographic analysis. Furthermore, the inhibitory mechanisms of Bofutrelvir against two SARS-CoV-2 Mpro mutants (G15S and K90R) were also elucidated through FRET and crystallographic studies. Through detailed analysis and comparison of these crystal structures, we identified crucial structural determinants of inhibition and elucidated the binding mode of Bofutrelvir to Mpros from different coronaviruses. These findings are hopeful to accelerate the development of safer and more potent inhibitors against the Mpro of coronavirus, and to provide important references for the prevention and treatment of similar viruses that may emerge in the future.

Long Dynamic β1-β2 Loops in M. tb MazF Toxins Affect the Interaction Modes and Strengths of the Toxin-Antitoxin Pairs.

Tuberculosis is a worldwide plague caused by the pathogen Mycobacterium tuberculosis (M. tb). Toxin-antitoxin (TA) systems are genetic elements abundantly present in prokaryotic organisms and regulate important cellular processes. MazEF is a TA system implicated in the formation of "persisters cells" of M. tb, which contain more than 10 such members. However, the exact function and inhibition mode of each MazF are not fully understood. Here we report crystal structures of MazF-mt3 in its apo form and in complex with the C-terminal half of MazE-mt3. Structural analysis suggested that two long but disordered β1-β2 loops would interfere with the binding of the cognate MazE-mt3 antitoxin. Similar loops are also present in the MazF-mt1 and -mt9 but are sustainably shortened in other M. tb MazF members, and these TA pairs behave distinctly in terms of their binding modes and their RNase activities. Systematic crystallographic and biochemical studies further revealed that the biochemical activities of M. tb toxins were combined results between the interferences from the characteristic loops and the electrostatic interactions between the cognate TA pairs. This study provides structural insight into the binding mode and the inhibition mechanism of the MazE/F TA pairs, which facilitate the structure-based peptide designs.

CaY@C2n: Exploring Molecular Qubits with Ca-Y Metal-Metal Bonds.

Metal-metal bonding is crucial in chemistry for advancing our understanding of the fundamental aspects of chemical bonds. Metal-metal bonds based on alkaline-earth (Ae) elements, especially the heavier Ae elements (Ca, Sr, and Ba), are rarely reported due to their high electropositivity. Herein, we report two heteronuclear di-EMFs CaY@Cs(6)-C82 and CaY@C2v(5)-C80, which contain unprecedented single-electron Ca-Y metal-metal bonds. These compounds were characterized by single-crystal X-ray crystallography, electron paramagnetic resonance (EPR) spectroscopy, and DFT calculations. The crystallographic study of CaY@Cs(6)-C82 shows that Ca and Y are successfully encapsulated into the carbon cage with a Ca-Y distance of 3.691 Å. The CW-EPR study of both CaY@Cs(6)-C82 and CaY@C2v(5)-C80 exhibits a doublet, suggesting the presence of an unpaired electron located between Ca and Y. The combined experimental and theoretical results confirm the presence of a Ca-Y single-electron metal-metal bond with substantial covalent interaction, attributed to significant overlap between the 4s4p orbitals of Ca and the 5s5p4d orbitals of Y. Furthermore, pulse EPR spectroscopy was used to investigate the quantum coherence of the electron spin within this bond. The unpaired electron, characterized by its s orbital nature, is effectively protected by the carbon cage, resulting in efficient suppression of both spin-lattice relaxation and decoherence. CaY@Cs(6)-C82 behaves as an electron spin qubit, displaying a maximum decoherence time of 7.74 μs at 40 K. This study reveals an unprecedented Ae-rare-earth metal-metal bond stabilized by the fullerene cages and elucidates the molecular qubit properties stemming from their unique bonding character, highlighting their potential in quantum information processing applications.

A second life for the crystallographic structure of Berenil-dodecanucleotide complex: a computational revisitation thirty years after its publication

AbstractThis study revisits the pioneering work of Professor Neidle, and co-workers, on the crystal structure of complexes formed between groove binders and DNA sequences. The original research revealed a DNA-ligand complex consisting of a dodecanucleotide bound with Berenil [1,3-bis(4′-amidinophenyl)-triazene] an anti-trypanocidal drug. This article aims to delve deeper into the structural dynamics of this system, showcasing the role played by water molecules in stabilizing the interaction between the ligand and the DNA. With this work, we reevaluate the findings from the original crystallographic study by employing modern molecular dynamics techniques, including Supervised Molecular Dynamics (SuMD) for generating binding trajectories, Thermal Titration Molecular Dynamics for assessing unbinding events, and AquaMMapS to identify regions occupied by stationary water molecules. The study addresses a minor and a major groove binding mode and assesses their strength and specificity using TTMD simulations, generating unbinding trajectories. This comprehensive approach integrates the understanding of the interaction of this DNA-ligand complex, which originated with the valuable work of Professor Neidle, resulting in an in-depth insight into the pivotal role of water molecules with this DNA, a behavior detected and extendable even to other nucleic acid complexes.

Mechanistic Insights from the Crystal Structure and Computational Analysis of the Radical SAM Deaminase DesII.

Radical S-adenosyl-L-methionine (SAM) enzymes couple the reductive cleavage of SAM to radical-mediated transformations that have proven to be quite broad in scope. DesII is one such enzyme from the biosynthetic pathway of TDP-desosamine where it catalyzes a radical-mediated deamination. Previous studies have suggested that this reaction proceeds via direct elimination of ammonia from an α-hydroxyalkyl radical or its conjugate base (i.e., a ketyl radical) rather than 1,2-migration of the amino group to form a carbinolamine radical intermediate. However, without a crystal structure, the active site features responsible for this chemistry have remained largely unknown. The crystallographic studies described herein help to fill this gap by providing a structural description of the DesII active site. Computational analyses based on the solved crystal structure are consistent with direct elimination and indicate that an active site glutamate residue likely serves as a general base to promote deprotonation of the α-hydroxyalkyl radical intermediate and elimination of the ammonia group.

Structural study of minor C84 isomers as chlorofullerenes, C84(11)Cl22, C84(14)Cl22, C84(16)Cl22, and C84(16)Cl24

Chlorofullerenes C84Cl22,24 were obtained by chlorination of minor C84 isomers mixture with VCl4 at 330 °C. An X-ray crystallographic study with the use of synchrotron radiation revealed the presence of C84(11)Cl22, C84(14)Cl22, C84(16)Cl22, and C84(16)Cl24 in the same crystal.

What a Difference an Electron Makes: Structural Response of Saddle‐Shaped Tetraphenylene to One and Two Electron Uptake

AbstractCyclooctatetraene (COT) and COT2− dianion are well‐known as archetypical non‐aromatic and aromatic systems, respectively. However, despite a wealth of studies the effect of one electron addition to the eight‐membered ring remains equivocal. Herein, we report the first stepwise electron addition to tetrabenzo[a,c,e,g]cyclooctatetraene (TBCOT or tetraphenylene), accompanied by isolation and structural characterization of the mono‐ and doubly‐reduced anions. The X‐ray crystallographic study reveals only a small asymmetric distortion of the saddle‐shaped core upon one electron uptake. In contrast, the doubly‐reduced product exhibits a severely twisted conformation, with a new C−C bond separating the COT ring into two fused 5‐membered rings. The reversibility of the two‐fold reduction and bond rearrangement is demonstrated by NMR spectroscopy. In agreement with experimental results, computational analysis confirms that the reduction‐induced core rearrangement requires the addition of the second electron.