X-ray Crystallographic Studies Research Articles

Sulfonamide diuretic azosemide as an efficient carbonic anhydrase inhibitor

Azosemide, a sulfonamide loop diuretic, has been investigated in vitro as inhibitor of human Carbonic Anhydrases (hCAs, EC 4.2.1.1). The inhibition profile shows the same high potency as the structural analog loop diuretic furosemide towards the most abundant isoforms hCA I and hCA II. On the other hand, replacement of the carboxylic group of furosemide with the tetrazole bioisostere in azosemide leads to important differences in activity for other isoforms such as hCA XII and in particular against hCA IV and XIV, thus explaining possible differences of potency in vivo. The higher inhibitory potency of azosemide compared to furosemide and bumetamide against hCA VII might also explain its efficacy in the management of epilepsy. By means of X-ray crystallographic studies we elucidated the binding mode of azosemide to hCA I and hCA II, which is rather different from that of furosemide when considering the thienylmethylamino and furanylmethylamino fragments present in the two diuretics.

Photochemical Synthesis of Transition Metal-Stabilized Uranium(VI) Nitride Complexes

Uranium nitrides play important roles in dinitrogen activation and functionalization and in chemistry for nuclear fuels, but the synthesis and isolation of the highly reactive uranium(VI) nitrides remains challenging. Here, we report an example of transition metal (TM) stabilized U(VI) nitride complexes, which are generated by the photolysis of azide-bridged U(IV)-TM (TM = Rh, Ir) precursors. The U(V) nitride intermediates with bridged azide ligands are isolated successfully by careful control of the irradiation time, suggesting that the photolysis of azide-bridged U(IV)-TM precursors is a stepwise process. The presence of two U(VI) nitrides stabilized by three TMs is clearly demonstrated by an X-ray crystallographic study. These TM stabilized U(V) nitride intermediates and U(VI) nitride products exhibit excellent stability both in the solid-state and in THF solution under ambient light. Density functional theory calculations show that the photolysis necessary to break the N-N bond of the azide ligands implies excitation from uranium f-orbital to the lowest unoccupied molecular orbital (LUMO), as suggested by the strong antibonding N-(N2) character present in the latter.

Homodimerization Counteracts the Detrimental Effect of Nitrogenous Heme Ligands on the Enzymatic Activity of Acanthamoeba castellanii CYP51.

Acanthamoeba castellanii is a free-living amoeba that can cause severe eye and brain infections in humans. At present, there is no uniformly effective treatment for any of these infections. However, sterol 14α-demethylases (CYP51s), heme-containing cytochrome P450 enzymes, are known to be validated drug targets in pathogenic fungi and protozoa. The catalytically active P450 form of CYP51 from A. castellanii (AcCYP51) is stabilized against conversion to the inactive P420 form by dimerization. In contrast, Naegleria fowleri CYP51 (NfCYP51) is monomeric in its active P450 and inactive P420 forms. For these two CYP51 enzymes, we have investigated the interplay between the enzyme activity and oligomerization state using steady-state and time-resolved UV-visible absorption spectroscopy. In both enzymes, the P450 → P420 transition is favored under reducing conditions. The transition is accelerated at higher pH, which excludes a protonated thiol as the proximal ligand in P420. Displacement of the proximal thiolate ligand is also promoted by adding exogenous nitrogenous ligands (N-ligands) such as imidazole, isavuconazole, and clotrimazole that bind at the opposite, distal heme side. In AcCYP51, the P450 → P420 transition is faster in the monomer than in the dimer, indicating that the dimeric assembly is critical for stabilizing thiolate coordination to the heme and thus for sustaining AcCYP51 activity. The spectroscopic experiments were complemented with size-exclusion chromatography and X-ray crystallography studies. Collectively, our results indicate that effective inactivation of the AcCYP51 function by azole drugs is due to synergistic interference with AcCYP51 dimerization and promoting irreversible displacement of the proximal heme-thiolate ligand.

Abstract 4059: Design and in vitro antitumor analysis of a novel diphenyltin complex (diphenyltin dioxalate)

Abstract Organotins are popular among chemists due to their potential biological properties against bacteria, fungus, and cancer cell lines. In particular, organotins have been utilized in chemotherapeutic applications. Compared to cisplatin, organotins give more favorable toxicological profiles and better cytotoxicity and antiproliferative activities. However, organotins have limited biological applications due to their poor water solubility. In this study we synthesized a diphenyltin complex (Diphenyltin Dioxalate) that possesses partial ionic characteristics, by reacting a diprotic carboxylic acid, with triphenyltin chloride in the presence of di-isopropylamine. A tin-carbon cleavage reaction was observed, as IR/NMR spectroscopy and X-ray Crystallography studies showed that diphenyltin dioxalate was successfully obtained in the reaction. Post synthesis solubility tests were performed to examine diphenyltin dioxalate’s water-soluble nature, compared to its precursor triphenyltin. Diphenyltin dioxalate was then tested to examine its cytotoxicity and antitumor activity on human glioblastoma cell model (T98G) and a normal human oligodendrocyte cell model (MO3.13). Further studies with the complex will consist of synthetic mechanistic studies on the Sn-C cleavage. Citation Format: Jade Witter, Xuequing Song, Alexandra Taraboletti, William Li, Tajera Henry. Design and in vitro antitumor analysis of a novel diphenyltin complex (diphenyltin dioxalate) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4059.

Dolabrane-Type Diterpenoids with Immunosuppressive Activity from Koilodepas hainanense.

Thirteen new dolabrane-type diterpenoids, koilodenoids A-M (1-13), including a chlorinated congener (2), along with six known analogues, were isolated from Koilodepas hainanense. The structures were determined by analysis of spectroscopic data, ECD spectra, and X-ray crystallographic studies. The absolute configuration of C-15 in the 15,16-diol unit of compounds 4 and 5 was established by using the dimolybdenum tetraacetate [Mo2(AcO)4]-induced ECD method. Compounds 4, 7, 16, 17, and 19 showed moderate to significant immunosuppressive activities against the proliferation of T and B lymphocytes in vitro, with compound 16 being the most potent (IC50 0.86 and 0.29 μM, respectively).

New Structural and Mechanistic Insights Into Functional Roles of Cytochrome b 559 in Photosystem II.

Cytochrome (Cyt) b559 is a key component of the photosystem II (PSII) complex for its assembly and proper function. Previous studies have suggested that Cytb559 has functional roles in early assembly of PSII and in secondary electron transfer pathways that protect PSII against photoinhibition. In addition, the Cytb559 in various PSII preparations exhibited multiple different redox potential forms. However, the precise functional roles of Cytb559 in PSII remain unclear. Recent site-directed mutagenesis studies combined with functional genomics and biochemical analysis, as well as high-resolution x-ray crystallography and cryo-electron microscopy studies on native, inactive, and assembly intermediates of PSII have provided important new structural and mechanistic insights into the functional roles of Cytb559. This mini-review gives an overview of new exciting results and their significance for understanding the structural and functional roles of Cytb559 in PSII.

Copper(II) NHC Catalyst for the Formation of Phenol from Arylboronic Acid.

Arylboronic acids are commonly used in modern organic chemistry to form new C-C and C-heteroatom bonds. These activated organic synthons show reactivity with heteroatoms in a range of substrates under ambient oxidative conditions. This broad reactivity has limited their use in protic, renewable solvents like water, ethanol, and methanol. Here, we report our efforts to study and optimize the activation of arylboronic acids by a copper(II) N-heterocyclic carbene (NHC) complex in aqueous solution and in a range of alcohols to generate phenol and aryl ethers, respectively. The optimized reactivity showcases the ability to make targeted C-O bonds, but also identifies conditions where water and alcohol activation could be limiting for C-C and C-heteroatom bond-forming reactions. This copper(II) complex shows strong reactivity toward arylboronic acid activation in aqueous medium at ambient temperature. The relationship between product formation and temperature and catalyst loading are described. Additionally, the effects of buffer, pH, base, and co-solvent are explored with respect to phenol and ether generation reactions. Characterization of the new copper(II) NCN-pincer complex by X-ray crystallography, HR-MS, cyclic voltammetry, FT-IR and UV-Vis spectral studies is reported.

H2BZmacropa-NCS: A Bifunctional Chelator for Actinium-225 Targeted Alpha Therapy.

Actinium-225 (225Ac) is one of the most promising radionuclides for targeted alpha therapy (TAT). With a half-life of 9.92 days and a decay chain that emits four high-energy α particles, 225Ac is well-suited for TAT when conjugated to macromolecular targeting vectors that exhibit extended in vivo circulation times. The implementation of 225Ac in these targeted constructs, however, requires a suitable chelator that can bind and retain this radionuclide in vivo. Previous work has demonstrated the suitability of a diaza-18-crown-6 macrocyclic chelator H2macropa for this application. Building upon these prior efforts, in this study, two rigid variants of H2macropa, which contain either one (H2BZmacropa) or two (H2BZ2macropa) benzene rings within the macrocyclic core, were synthesized and investigated for their potential use for 225Ac TAT. The coordination chemistry of these ligands with La3+, used as a nonradioactive model for Ac3+, was carried out. Both NMR spectroscopic and X-ray crystallographic studies of the La3+ complexes of these ligands revealed similar structural features to those found for the related complex of H2macropa. Thermodynamic stability constants of the La3+ complexes, however, were found to be 1 and 2 orders of magnitude lower than those of H2macropa for H2BZmacropa and H2BZ2macropa, respectively. The decrease in thermodynamic stability was rationalized via the use of density functional theory calculations. 225Ac radiolabeling and serum stability studies with H2BZmacropa showed that this chelator compares favorably with H2macropa. Based on these promising results, a bifunctional version of this chelator, H2BZmacropa-NCS, was synthesized and conjugated to the antibody codrituzumab (GC33), which targets the liver cancer biomarker glypican-3 (GPC3). The resulting GC33-BZmacropa conjugate and an analogous GC33-macropa conjugate were evaluated for their 225Ac radiolabeling efficiencies, antigen-binding affinities, and in vivo biodistribution in HepG2 liver cancer tumor-bearing mice. Although both conjugates were comparably effective in their radiolabeling efficiencies, [225Ac]Ac-GC33-BZmacropa showed slightly poorer serum stability and biodistribution than [225Ac]Ac-GC33-macropa. Together, these results establish H2BZmacropa-NCS as a new bifunctional chelator for the preparation of 225Ac radiopharmaceuticals.

Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy.

Aminoacyl tRNA synthetases (aaRSs) are attractive drug targets. Here we show that class I and II aaRSs are previously unrecognized targets for AMP-mimicking nucleoside sulfamates. The target enzyme catalyzes the formation of an inhibitory amino acid-sulfamate conjugate, via a reaction-hijacking mechanism. We identified adenosine 5′-sulfamate (AMS) as a broad specificity compound that hijacks a range of aaRSs; and ML901 as a specific reagent that hijacks a single aaRSs in the malaria parasite, Plasmodium falciparum, namely, tyrosine RS (PfYRS). ML901 exerts whole-of-life-cycle killing activity with low nanomolar potency and single dose efficacy in a mouse model of malaria. X-ray crystallographic studies of plasmodium and human YRSs reveal differential flexibility of a loop over the catalytic site that underpins differential susceptibility to reaction-hijacking by ML901.

Stilbenes from the leaves of Cajanus cajan and their in vitro anti-inflammatory activities

Eighteen stilbenes (1–18), including six previously undescribed ones (1–6), with diverse modification patterns were isolated from the leaves of edible and medicinal plant Cajanus cajan. Among the new isolates, compounds 1–3 were initially obtained as three racemic mixtures, which were further resolved into three pairs of optically pure enantiomers, respectively, by chiral HPLC. Besides, compounds 8, 10, 11, and 18 were obtained from C. cajan for the first time. The chemical structures and absolute configurations of the new stilbenes were elucidated unambiguously on the basis of extensive spectroscopic analyses, single crystal X-ray crystallographic study, and quantum chemical electronic circular dichroism (ECD) calculations. In addition, the in vitro anti-inflammatory activities of all isolated stilbenes were evaluated. Compounds 2, 9, 10, 11, and 14 exerted moderate suppression of nitric oxide (NO) secretion in lipopolysaccharide (LPS)-induced RAW264.7 cells without exhibiting substantial cytotoxicity.

Mapping the Assembly of Neutral Tetrahedral Cages Tethered by Oximido Linkers and Their Guest Encapsulation Studies.

A primary criterion for the design of polyhedral metal-organic cages is the requirement of geometrically matched pairs of metal ions and ligand moieties. However, understanding the pathway it takes to reach the final polyhedral structure can provide more insights into the self-assembly process and improved design strategies. In this regard, we report two neutral tetrahedral cages with the formulas {[Pd3(NiPr)3PO]4(L1)6} (1-TD) and {[Pd3(NiPr)3PO]4(L2)6} (2-TD) starting from the acetate-bridged cluster {[Pd3(NiPr)3PO]2(OAc)2(OH)}2·2(CH3)2SO (HEXA-Pd) and the respective oxamide precursors (L1H2: [C2(NH2)2O2]) and (L2H2: (C2(NHMe)2O2]). When subtle variations in the reaction conditions were made, two new tetrameric Pd12 assemblies, {[Pd3(NiPr)3PO]4(L1)2(OAc)4(OMe)4} (1-TM) and {[Pd3(NiPr)3PO]4(L2)2(OAc)4(OMe)4} (2-TM), were obtained from the same precursors. Detailed investigations using NMR, mass spectrometry, X-ray crystallography, and computational studies indicate that the macrocyclic complexes 1-TM and 2-TM are the reaction intermediates involved in the formation of the tetrahedral cages 1-TD and 2-TD, respectively. Moreover, the tetrahedral cages 1-TD and 2-TD exhibited intrinsic cavities of volume ∼85 Å3. Guest encapsulation studies revealed that the cage 1-TD can encapsulate a wide range of guest molecules such as CH2Cl2, CHCl3, CCl4, C6H6, and C6H5F. Interestingly, 1-TD was shown to exhibit a preferential binding of C6H5F and C6H6 over other halogenated guest molecules, as determined from NMR titrations and computational studies.

Borylated 2,3,4,5-Tetrachlorophthalimide and Their 2,3,4,5-Tetrachlorobenzamide Analogues: Synthesis, Their Glycosidase Inhibition and Anticancer Properties in View to Boron Neutron Capture Therapy.

Tetrachlorinated phthalimide analogues bearing a boron-pinacolate ester group were synthesised via two synthetic routes and evaluated in their glycosidase modulating and anticancer properties, with a view to use them in boron neutron capture therapy (BNCT), a promising radiation type for cancer, as this therapy does little damage to biological tissue. An unexpected decarbonylation/decarboxylation to five 2,3,4,5-tetrachlorobenzamides was observed and confirmed by X-ray crystallography studies, thus, giving access to a family of borylated 2,3,4,5-tetrachlorobenzamides. Biological evaluation showed the benzamide drugs to possess good to weak potencies (74.7–870 μM) in the inhibition of glycosidases, and to have good to moderate selectivity in the inhibition of a panel of 18 glycosidases. Furthermore, in the inhibition of selected glycosidases, there is a core subset of three animal glycosidases, which is always inhibited (rat intestinal maltase α-glucosidase, bovine liver β-glucosidase and β-galactosidase). This could indicate the involvement of the boron atom in the binding. These glycosidases are targeted for the management of diabetes, viral infections (via a broad-spectrum approach) and lysosomal storage disorders. Assays against cancer cell lines revealed potency in growth inhibition for three molecules, and selectivity for one of these molecules, with the growth of the normal cell line MCF10A not being affected by this compound. One of these molecules showed both potency and selectivity; thus, it is a candidate for further study in this area. This paper provides numerous novel aspects, including expedited access to borylated 2,3,4,5-tetrachlorophthalimides and to 2,3,4,5-tetrachlorobenzamides. The latter constitutes a novel family of glycosidase modulating drugs. Furthermore, a greener synthetic access to such structures is described.

Copper(II) Schiff base complex derived from salen ligand: structural investigation, Hirshfeld surface analysis, anticancer and anti-SARS-CoV-2

This work deals with the synthesis and characterization of copper(II) complex [Cu(salen)(H2O)](1) of salen-type Schiff base ligand derived from the condensation of 5-bromo-2-hydroxy-3-methoxybenzaldehyde and ethylenediamine in EtOH. This complex was characterized by different spectroscopic and physicochemical methods. Single crystal X-ray crystallography study revealed that Cu(II) in complex (1) is five-coordinate and adopts a distorted square pyramidal geometry. A DFT calculation was employed to evaluate the optimized electronic structure, HOMO-LUMO, energy gap, and global parameters. A detailed structural and non-covalent interaction on the complex is investigated by single crystal structure analysis and computational approaches. The strength of the interaction and 3D topology of the crystal packing are visualized through an energy framework. Hirshfeld surface and 2D fingerprint plots have been explored in the crystal structure of the complex. The anticancer properties of copper(II) complex was studied against the selected cancerous cell lines of breast cancer, cervical cancer, colon cancer and hepatocellular carcinoma. Additionally, molecular docking and MD simulations was performed on the complex to predict the binding mode and interactions between the ligand and the main protease of the SARS-CoV-2 (PDB ID: 7CBT and 7D1M). The molecular docking calculations of the complex (1) with SARS-CoV-2 virus revealed the binding energy of –8.1 kcal/mol and –7.5 kcal/mol with an inhibition constant of 3.245 µM and 2.318 µM at inhibition binding site of receptor towards 7CBT and 7D1M main protease (Mpro), respectively. Besides this, molecular docking results (–7.6 kcal/mol, 3.196 µM) towards Escherichia coli PBP2 targets (PDB ID: 6G9S) was also studied. Communicated by Ramaswamy H. Sarma

Lanthanide coordination polymers functionalized by 5-nitroisophthalic acid: Synthesis, structure-DFT correlation and photoluminescent sensor of Cd2+ ion

Lanthanide coordination polymers (LnCPs) are influential chemosensors when designed to undergo a detectable change in optical properties upon interacting with target analytes. This work reports interaction of metal ions with LnCPs leading to elicit changes in fluorescence emission intensity, an essential step en route to developing sensitive and selective systems for metal-ion sensing. Towards this goal, solvothermal reaction of 5- Nitroisophthalic Acid (5-NIAH2) and Ln (NO3)3⋅xH2O produced seven Ln-coordination polymers {[Nd (5-NIA) (5-NIAH) (H2O)2]⋅CH3CN}n (1), {[Sm (5-NIA) (5-NIAH) (H2O)2]⋅CH3CN⋅H2O}n (2), {[Gd (5-NIA) (5-NIAH) (H2O)2]⋅(H2O)2}n (3), {[Tb (5-NIA) (5-NIAH) (H2O)2]⋅CH3CN)}n (4), [Dy (5-NIA) (5-NIAH) (H2O)2]n (5), [Ho(5-NIA) (5-NIAH) (H2O)2]n (6) and [Er2 (5-NIA)3(H2O)3(CH3CN)]n (7) with two-dimensional structures. The as-synthesized polymers are characterized by powder X-ray crystallography, infrared spectroscopy, thermogravimetric analysis, photoluminescence and DFT studies. The luminescence properties of [Tb (5-NIA) (5-NIAH) (H2O)2]⋅CH3CN)}n (4) is investigated. The CP-4 is highly sensitive for the detection of Cd2+ exhibiting most intensive fluorescence quenching with the lowest limit of detection. Other metal ions, including Co2+, Fe3+, Fe2+ and Pb2+ are also detected demonstrating the range of sensing capabilities.

Protein-protein and protein-lipid interactions of pore-forming BCL-2 family proteins in apoptosis initiation.

Apoptosis is a common cell death program that is important in human health and disease. Signaling in apoptosis is largely driven through protein-protein interactions. The BCL-2 family proteins function in protein-protein interactions as key regulators of mitochondrial poration, the process that initiates apoptosis through the release of cytochrome c, which activates the apoptotic caspase cascade leading to cellular demolition. The BCL-2 pore-forming proteins BAK and BAX are the key executors of mitochondrial poration. We review the state of knowledge of protein-protein and protein-lipid interactions governing the apoptotic function of BAK and BAX, as determined through X-ray crystallography and NMR spectroscopy studies. BAK and BAX are dormant, globular α-helical proteins that participate in protein-protein interactions with other pro-death BCL-2 family proteins, transforming them into active, partially unfolded proteins that dimerize and associate with and permeabilize mitochondrial membranes. We compare the protein-protein interactions observed in high-resolution structures with those derived in silico by AlphaFold, making predictions based on combining experimental and in silico approaches to delineate the structural basis for novel protein-protein interaction complexes of BCL-2 family proteins.

Altering NAD(P)H cofactor specificity by structure‐guided modification of class II HMG‐CoA reductase

HMG‐CoA reductase (HMGR) is a central enzyme in metabolism and natural product biosynthesis, as it catalyzes the committed and rate‐determining step of the mevalonate pathway, which produces steroids and isoprenoids, the largest and most diverse class of natural products. Here, HMGR converts HMG‐CoA to mevalonate using two equivalents of a redox cofactor, either NADH or NADPH. Class I HMGRs are highly specific for NADPH, including human HMGR, the target of cholesterol‐lowering statin drugs. However, cofactor specificity of microbial class II HMGR varies widely, as some homologs exhibit a strong preference for either NADH or NADPH, while others homologs are less specific. We have recently identified a key structural feature termed the “cofactor helix” that may govern cofactor specificity in class II HMGR, but until now this helix’s role in conferring NAD(P)H preference has not been tested. In this work, we performed structure‐guided enzyme modification with the aim of altering the cofactor preferences of various class II HMGR homologs. Through kinetic and X‐ray crystallographic studies on these enzyme variants, we have found that the cofactor helix plays a critical but not exclusive role in controlling NAD(P)H preference, expanding our understanding of the structural determinants of cofactor specificity in class II HMGR.

Fluorescent Cu2+ sensor based on phenanthroline-BODIPY conjugate: A mechanistic study

Development of a specific Cu2+ sensor for the detection of labile Cu2+ ions in vivo in the presence of labile pools of other biologically important metal ions is a real challenge due to similar binding affinity of these metal ions with the ligands containing N and O donor atoms. Here, we designed and synthesized a mixed N- and O-donor atoms containing BODIPY-phenanthroline conjugate where two BODIPY dyes are linked at 2 and 9 position of 1,10-phenanthroline moiety through amide linkage. NMR and X-ray crystallography studies were done to characterize the dye structure. Phenanthroline is a known binder of different metal ions without much selectivity, but the new ligand shows highly selective detection of Cu2+ ions via fluorescent turn off mechanism without any interference with other biologically important metal ions. The sensing mechanism was investigated by detailed photochemical, electrochemical, NMR, FTIR, MALDI-TOF and DFT studies. The BODIPY-phenanthroline conjugate forms 1:1 complex with the Cu2+ ion which is confirmed by NMR, MS and DFT studies. Importantly, both dynamic and static quenching processes are responsible for the fluorescence attenuation of the BODIPY-phenanthroline conjugate in the presence of Cu2+ ions. The new ligand is cell-permeable and non-toxic to the cells under tested concentrations. Finally, its potential application to monitor cellular accumulation of Cu2+ ions and detection of Cu2+ in serum samples are also investigated and discussed.

Design, synthesis and characterization of novel Ni(II) and Cu(II) complexes as antivirus drug candidates against SARS-CoV-2 and HIV virus

This paper describes the structure-based design, synthesis and anti-virus effect of two new coordination complexes, a Ni(II) complex [Ni(L)2] (1) and a Cu(II) complex [Cu(L)2] (2) of (E)-N-phenyl-2-(thiophen-2-ylmethylene) hydrazine-1-carbothioamide(HL). The synthesized ligand was coordinated to metal ions through the bidentate-N, S donor atoms. The newly synthesized complexes were characterized by various spectroscopic and physiochemical methods, powdered XRD analysis and also X-ray crystallography study. Ni(II) complex [Ni(L)2](1) crystallize in orthorhombic crystal system with the space group Pbca with four molecules in the unit cell (a = 9.857(3) Å, b = 7.749(2) Å, c = 32.292(10) Å, α = 90°, β = 90°, γ = 90°, Z= 4) and reveals a distorted square planar geometry. A Hirshfeld surface and 2D fingerprint plot has been explored in the crystal structure of Ni(II) complex [Ni(L)2] (1). Energy framework computational analysia has also been explored. DFT based calculations have been performed on the Schiff base and its metal complexes to study the structure-property relationship. Furthermore, the molecular docking studies of the ligand and its metal complexes with SARS-CoV-2 virus (PDB ID: 7BZ5) and HIV-1 virus (PDB ID: 6MQA) are also investigated. The molecular docking calculations of the Ni(II) complex [Ni(L)2] (1) and a Cu(II) complex [Cu(L)2] (2) with SARS-CoV-2 virus revealed that the binding affinities at inhibition binding site of receptor protein are 9.7 kcal/mol and -9.3 kcal/mol, respectively. The molecular docking results showed that the binding affinities of Ni(II) complex (1) and Cu(II) complex (2) against SARS-CoV-2 virus were found comparatively higher than the HIV-1 virus (-8.5 kcal/mol and -8.2 kcal/mol, respectively). As potential drug candidates, Swiss-ADME predictions analyses are also studied and the results are compared with Chloroquine (CQ) and Hydroxychloroquine (HCQ) as anti-SARS-CoV-2 drugs.

Bärnighausen Trees – A group–subgroup reference database

Abstract Group–subgroup schemes are a useful tool in crystal chemistry for systemizing crystal structures and they are an indispensable help during X-ray crystallographic studies of complex, twinned and modulated structures. Meanwhile many superstructure variants are summarized within so-called Bärnighausen trees. The present database lists relevant literature with respect to the crystallographic/group-theoretical tools and original work and gives a tabulated overview on the crystallographic fingerprints (aristotype, space group symbol, Pearson code and Wyckoff sequence) of the respective superstructures.

Long-Duration Crystal-Jumping by a Stepwise Stimulation: Thermal Induction of Strain and Its Release by Spontaneous Desolvation

Abstract Here we report thermally-induced and long-duration jumping phenomena in a toluene-solvated crystal of zinc(II) tetraphenylporphyrin. The crystal splits into pieces along with a jumping phenomenon by cooling after heating over its desolvation temperature. Interestingly, the jumping phenomenon was observed for more than a few minutes after the thermal stimulus. Microscope observations, thermal analyses, and X-ray crystallographic studies revealed that the long-duration jumping phenomenon is due to a stepwise stimulation: accumulation of thermally-induced strain by coexisting the solvated and unsolvated crystal structures, i.e. pseudo-polymorphs, in the crystal and release of the strain triggered by time, i.e. gradual spontaneous desolvation at the ambient conditions. Our findings based on the stepwise approach demonstrate that time can work as a stimulus for jumping molecular crystals and demonstrate their designability by introduction of strain as an artificial modification.