X-ray Crystallographic Studies Research Articles

One RING to rule them all: Mind bomb-1 ccRING3 controls Notch signaling

In this issue of Structure, Cao etal.1 use X-ray crystallography, biochemical, and genetic studies to define the key role of the Mind bomb-1 ccRING3 domain in triggering Notch signaling, and they demonstrate that ccRING3-mediated dimerization is a key step in ligand activation.

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.

Synthesis and Performance Evaluation of Zwitterionic C-N Bonded Triazole-Tetrazole-Based Primary Explosives.

Developing advanced metal-free nitrogen-enriched primary explosives is challenging due to the inherent risks associated with their synthesis and handling. However, there is an urgent need to develop novel lead-free, nitrogen-rich primary explosives that offer balanced energetic properties. C-N bonded bicyclic compound 3-azido-1-(1H-tetrazol-5-yl)-1H-1,2,4-triazol-5-amine (4), its salts, and 3,5-diazido-1H-1,2,4-triazole (8) were synthesized from inexpensive starting materials resulting in a fine blend of sensitivity and stability. These compounds exhibit high nitrogen content (79.78 to 83.43%), good thermal stability (129-210 °C), excellent detonation performance (VOD: 8592-9361 ms-1, DP: 27.1-33.8 GPa), and acceptable sensitivity (IS: 2.5-30 J, FS: 72-288 N). The hot needle tests of compounds 4 and 8 exhibit excellent ignition performance. All of the newly synthesized compounds were fully characterized using infrared spectroscopy (IR), high-resolution mass spectroscopy (HRMS), multinuclear magnetic spectroscopy (NMR), elemental analysis (EA), thermogravimetric analysis-differential scanning calorimetry (TGA-DSC), and 2, 4, and 8 were confirmed by single-crystal X-ray crystallographic studies. The molecular electrostatic potential (ESP), noncovalent interactions reduced density gradient (NCI-RDG) method, and QTAIM analysis were performed to investigate the intermolecular interactions. Together with promising performance properties, ease of synthesis, and ignitability, they are highly suitable candidates to pave new avenues for future applications.

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. The3MLCT 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 emissivebehaviour with dihydrogenphosphate is variable, showing systematic changes as anion concentration increases with several distinct interactions evident .1H NMR and31P NMR titrations in a 10% D2O - D6-DMSO mixture suggest that with dihydrogenphosphate, the imidazole group 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.

Experimental and theoretical studies of pyrazole-4-carbaldehyde derivatives by X-ray crystallography, DFT, molecular docking, and molecular dynamics simulation

Nitrogen-containing heterocycles play a crucial role in drug design and discovery. Pyrazole derivatives have garnered attention due to their unique and intriguing features. This study investigates the structure and properties of two pyrazole-4-carbaldehyde derivatives (3 and 4). We report the single crystal structure of one of the intermediate compounds, 1-(1-(4-bromophenyl)ethylidene)-2-(2-chlorophenyl)hydrazine (2), and a final compound, 1-(2-chlorophenyl)-3-phenyl-1H-pyrazole-4-carbaldehyde (3). We analysed the non-covalent interactions within the crystal using Hirshfeld surface analysis and 2D fingerprint plots. We also used density functional theory (DFT) at the B3LYP/6–311G(d,p) level to optimise the structures and understand electronic properties, transitions and vibrational frequencies. To predict the anti-inflammatory potentials and selectivity of 3 and 4, molecular docking and molecular dynamics (MD) simulation studies against COX1 (PDB ID: 1EQG) and COX2 (PDB ID: 1CX2) receptors were conducted. Overall, this study sheds light on the structural, chemical, and biochemical features of two pyrazole-4-carbaldehyde derivatives.

Allosteric inhibition of IgE–FcεRI interactions by simultaneous targeting of IgE F(ab’)2 epitopes

Immunoglobulin E (IgE) plays pivotal roles in allergic diseases through interaction with a high-affinity receptor (FcεRI). We established that Fab fragments of anti-IgE antibodies (HMK-12 Fab) rapidly dissociate preformed IgE-FcεRI complexes in a temperature-dependent manner and inhibit IgE-mediated anaphylactic reactions, even after allergen challenge. X-ray crystallographic studies revealed that HMK-12 Fab interacts with each of two equivalent epitopes on the Cε2 homodimer domain involved in IgE F(ab’)2. Consequently, HMK-12 Fab-mediated targeting of Cε2 reduced the binding affinity of Fc domains and resulted in rapid removal of IgE from the receptor complex. This unexpected finding of allosteric inhibition of IgE-FcεRI interactions by simultaneous targeting of two epitope sites on the Cε2 homodimer domain of IgE F(ab’)2 may have implications for the development of novel therapies for allergic disease.

Cytotoxic diterpenoids from Croton kongensis inhibiting tumor proliferation and migration

Thirty-two diterpenoids including 18 ent-kauranes (1–6, and 12–23), nine 8,9-seco-ent-kauranes (7–8, and 24–30), four ent-abietanes (9–10, and 31–32), and one crotofolane (11) were isolated from the twigs and leaves of Croton kongensis. The structures of previously unreported crokokaugenoids A–H (1–8), crokoabiegenoids A–B (9–10), and crokocrotogenoid A (11) were determined by spectroscopic data analyses, TDDFT-ECD and GIAO NMR calculations, and X-ray crystallographic studies. All compounds were evaluated for their cytotoxic activity against five human tumor cell lines, and the structure–activity relationships were discussed. Biological tests exhibited that compound 1 possessed strong anti-proliferation activity, arrested cell cycle at G2/M phase, and induced cell apoptosis of MDA-MB-231. The mechanism investigation showed that compound 1 can inhibit tumor proliferation and migration by targeting mitochondria to increase intracellular reactive oxygen species (ROS) and regulating STAT3 and FAK signal pathways. Collectively, these findings supported the great potential of compound 1 as a hopeful anticancer agent.

De novo design of miniprotein antagonists of cytokine storm inducers

Cytokine release syndrome (CRS), commonly known as cytokine storm, is an acute systemic inflammatory response that is a significant global health threat. Interleukin-6 (IL-6) and interleukin-1 (IL-1) are key pro-inflammatory cytokines involved in CRS and are hence critical therapeutic targets. Current antagonists, such as tocilizumab and anakinra, target IL-6R/IL-1R but have limitations due to their long half-life and systemic anti-inflammatory effects, making them less suitable for acute or localized treatments. Here we present the de novo design of small protein antagonists that prevent IL-1 and IL-6 from interacting with their receptors to activate signaling. The designed proteins bind to the IL-6R, GP130 (an IL-6 co-receptor), and IL-1R1 receptor subunits with binding affinities in the picomolar to low-nanomolar range. X-ray crystallography studies reveal that the structures of these antagonists closely match their computational design models. In a human cardiac organoid disease model, the IL-1R antagonists demonstrated protective effects against inflammation and cardiac damage induced by IL-1β. These minibinders show promise for administration via subcutaneous injection or intranasal/inhaled routes to mitigate acute cytokine storm effects.

Comprehensive review on Haloalkane dehalogenase (LinB): a β-hexachlorocyclohexane (HCH) degrading enzyme.

Haloalkane dehalogenase, LinB, is a member of the α/β hydrolase family of enzymes. It has a wide range of halogenated substrates, but, has been mostly studied in context of degradation of hexachlorocyclohexane (HCH) isomers, especially β-HCH (5-12% of total HCH isomers), which is the most recalcitrant and persistent among all the HCH isomers. LinB was identified to directly act on β-HCH in a one or two step transformation which decreases its toxicity manifold. Thereafter, many studies focused on LinB including its structure determination using X-ray crystallographic studies, structure comparison with other haloalkane dehalogenases, substrate specificity and kinetic studies, protein engineering and site-directed mutagenesis studies in search of better catalytic activity of the enzyme. LinB was mainly identified and characterized in bacteria belonging to sphingomonads. Detailed sequence comparison of LinB from different sphingomonads further revealed the residues critical for its activity and ability to catalyze either one or two step transformation of β-HCH. Association of LinB with IS6100 elements is also being discussed in detail in sphingomonads. In this review, we summarized vigorous efforts done by different research groups on LinB for developing better bioremediation strategies against HCH contamination. Also, kinetic studies, protein engineering and site directed mutagenesis studies discussed here forms the basis of further exploration of LinB's role as an efficient enzyme in bioremediation projects.

Lanthanide-based F-MOFs: Structure, hydrolytic stability, spectral and magnetic properties

A series of five novel lanthanide-based fluorinated metal-organic frameworks (Ln-F-MOFs) have been synthesized under solvothermal conditions by the reaction of 3,3′-bis(trifluoromethyl)-[1,1′-biphenyl]-4,4′-dicarboxylic acid (H2L) and lanthanide Ln(III) ions (Ln(III)La, Ce, Pr, Nd and Eu). Powder X-ray diffraction (PXRD) analysis revealed that all prepared complexes are isostructural. A single-crystal X-ray crystallographic study of one representative of the isostructural group, namely {[La2(L)3(DMF)2(H2O)2]}n showed, that compound crystallizes in a triclinic system with space group P-1. The lattice parameter values are a = 8.563(2) Å, b = 13.199(3) Å, c = 16.008(4) Å, α = 104.588(7) °, β = 92.904(7) ° and γ = 92.717(7) °, with two formula units in the unit cell. The overall structure is formed by 2D polymeric layers, which are arranged into a semi-3D supramolecular structure through hydrogen bonds and other intramolecular interactions. The study of the hydrophobic properties of the complexes showed that the complexes exhibit surface hydrophobicity with a “rose petal effect” and a contact angle of approximately 107°. However, the structures are not hydrolytically stable in the long term and the structure starts to delaminate after two days in water. This is a manifestation of the fact that the complexes do not form a 3D polymer network, it is made up of 2D layers connected only by weak non-bonding interactions. The photoluminescence properties of the Ln(III) complexes are determined by the characteristic 5d-4f or 4f-4f electron transitions for the individual lanthanide ions. The magnetic properties of Nd(III), Pr(III) and Eu(III) variants were studied. The magnetic properties of {[Pr2(L)3(DMF)2(H2O)2]}n are characterized by the presence of a low-lying quasi-doublet with 15.6 cm−1 energy splitting, whereas Eu(III) variant is nonmagnetic at low temperatures, but the magnetic 7F1 state is accessible by thermal excitation. For Nd(III) complex, the X-band EPR measurements were performed. Since 1D channels with dimensions of 4.90 × 7.23 Å2 are present within the structure, the adsorption of N2, CO2 and H2 gases was also studied.

Binary and Halide-free Catalyst Systems Based on Al/Ga/In Aminopyridylbisphenolate Complexes for the Cycloaddition of Epoxides and CO2.

Group 13 complexes bearing an aminopyridylbisphenol ligand have been prepared [ML-X; L = ligand, M = Al (X = Cl and Br), Ga (X = Cl, Br, and I), or In (X = Cl)]. The structures of the complexes containing the chloride ligand (ML-Cl; M = Al, Ga, and In) have been directly compared through an X-ray crystallography study, with differences in the monomeric or dimeric nature of their structures observed. All of the complexes obtained have been studied as potential catalysts for the synthesis of cyclic carbonates from epoxides and CO2. It has been found that the indium complex, as part of a traditional binary catalyst system (catalyst + tetra-butylammonium halide cocatalyst), displays the highest catalytic activity and is active under rather mild reaction conditions (balloon pressure of CO2). Meanwhile, it has been found that the GaL-I complex is a competent single-component catalyst (no need for addition of a cocatalyst) at more elevated reaction temperatures and pressures. A full substrate scope has been performed with both developed catalyst systems to demonstrate their applicability. In addition to the experimental results, a density functional theory study was performed on both catalyst systems. These results explain both why the indium catalyst is the most active under binary catalyst system conditions and how the gallium catalyst with an iodide (GaL-I) is able to act as a single-component catalyst in contrast to the indium-based complex.

Characterization of the Structural Requirements for the NADase Activity of Bacterial Toll/IL-1R domains in a Course-based Undergraduate Research Experience.

TLRs initiate innate immune signaling pathways via Toll/IL-1R (TIR) domains on their cytoplasmic tails. Various bacterial species also express TIR domain-containing proteins that contribute to bacterial evasion of the innate immune system. Bacterial TIR domains, along with the mammalian sterile α and TIR motif-containing protein 1 and TIRs from plants, also have been found to exhibit NADase activity. Initial X-ray crystallographic studies of the bacterial TIR from Acinetobacter baumannii provided insight into bacterial TIR structure but were unsuccessful in cocrystallization with the NAD+ ligand, leading to further questions about the TIR NAD binding site. In this study, we designed a Course-Based Undergraduate Research Experience (CURE) involving 16-20 students per year to identify amino acids crucial for NADase activity of A. baumannii TIR domain protein and the TIR from Escherichia coli (TIR domain-containing protein C). Students used structural data to identify amino acids that they hypothesized would play a role in TIR NADase activity, and created plasmids to express mutated TIRs through site-directed mutagenesis. Mutant TIRs were expressed, purified, and tested for NADase activity. The results from these studies provide evidence for a conformational change upon NAD binding, as was predicted by recent cryogenic electron microscopy and hydrogen-deuterium exchange mass spectrometry studies. Along with corroborating recent characterization of TIR NADases that could contribute to drug development for diseases associated with dysregulated TIR activity, this work also highlights the value of CURE-based projects for inclusion of a diverse group of students in authentic research experiences.

Oleanane-type triterpenoids from Sabia limoniacea and their anti-inflammatory activities

Eighteen new oleanane-type triterpenoids were isolated from the stems of Sabia limoniacea, including sabialimon A (1), a triterpenoid with an unprecedented 6/6/6/7/7 pentacyclic skeleton and seventeen undescribed triterpenoids, sabialimons B−R (2 − 18), along with six previously described analogs (19 − 24). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), experimental electronic circular dichroism measurements and X-ray crystallographic studies. Compound 1 is the first triterpenoid that possesses a rare ring system (6/6/6/7/7) with an oxygen-bearing bridge between C-17 and C-18 and a hemiketal form at C-17, which is generated a larger ring by the degradation of C-28 and D/E-ring expansion. Biological evaluation revealed that sabialimon I (9), sabialimon K (11), sabialimon P (16) and 11,13(18)-oleanadien-28-hydroxymethyl 3-one (20) exhibited significantly inhibitory activities against nitric oxide (NO) release with IC50 values of 29.65, 23.41, 18.12 and 26.64 μM, respectively, as compared with the positive control (dexamethasone, IC50 value: 40.35 μM). Furthermore, sabialimon P markedly decreased the secretion of TNF-α, iNOS, IL-6 and NF-κB and inhibited the expression of COX–2 and NF-κB/p65 in LPS-induced RAW264.7 cells in a dose-dependent manner.

Influence of aluminium in wetting characteristics of Zn-Al alloy

In this article, the effect of aluminium in Zn-5 wt%Al alloy is studied after heat treatment at 375 ⁰C focusing particularly on its effect at grain boundaries or grain boundary junctions. The understanding of such behaviour is crucial for microstructural controlling during alloy processing, ensuring better alloy performance for various applications. Using Scanning Electron Microscopy (SEM) and X-ray Diffraction (XRD), the microstructural and crystallographic study of the alloy was carried out. The SEM results of the annealed sample show a lenticular-shaped wetting layer corresponding to the lower energy of the grain boundary. It was observed that Zn is distributed throughout the sample, while the concentration of Al is increased at the grain boundaries as evidenced by the elemental spectra. XRD result confirms that no new phases are formed thereby confirming the formation of an Al-rich solid solution at the grain boundary. The absence of new phases indicates that aluminium in the alloy tends to lower grain boundary energy by occupying grain boundary positions, rather than forming a new compound, thereby reaching thermodynamic equilibrium. This study is important for developing advanced engineering materials with solid-state lubrication capabilities, for diverse industrial applications.

Harnessing the Reactivity of ortho-Alkynylaldehydes: Silver Triflate Catalyzed Regioselective Synthesis of Phosphonylated Fluorescent Molecules

AbstractAn efficient approach for the facile synthesis of phosphonylated 1,3-dihydrofuro[3,4-b]quinolines and dihydrofuro[3,4-b]pyridines is developed. Reaction proceeds by the formation of new C–P and C–O bonds affording Z-selective phosphonylated products at room temperature. Diphenylphosphine oxides and dialkyl phosphites are explicitly incorporated into the carbonyl carbon of o-alkynylaldehydes in good to excellent yields. The reaction exhibits mild conditions, broad substrate scope, and the formation of three new bonds in the presence of a silver catalyst. The mechanistic studies revealed that the reaction proceeded via an ionic pathway in a 5-exo-dig manner to give Z-selective products, which was validated by X-ray crystallographic studies. Photophysical studies of selected compounds revealed the emission maxima in the range of 455 nm.

Synthesis, structural, spectroscopic and theoretical insights into a new malononitrile derivative: A candidate for nonlinear optical applications

Functionalized alkylidene malononitriles play a crucial role as donor-acceptor molecules, exhibiting notable nonlinear optical (NLO) properties. Allylidene malononitriles, an analogue of alkylidene malononitriles, have not been explored before for their optical properties. The present work deals with the synthesis of (Z)-2-(3-(4-bromophenyl)-3-chloroallylidene) malononitrile using Knoevenagel condensation reaction of Z-3-(4-bromophenyl)-3-chloroacrylaldehyde and malononitrile. Structure of the compound was elucidated by single-crystal X-ray crystallography and related spectroscopic studies like FT-IR, NMR (1H, 13C), and UV–Vis spectroscopy, which were further supported with computational studies using Density Functional Theory (DFT) approach. The photoluminescence spectra showed that the compound exhibited an emission peak at 425 nm with an excitation wavelength of 352 nm. The single crystal study reveals that the compound belongs to a monoclinic system with space group P21/c. The thermal characteristics of the compound was analysed using TGA-DTA/DSC. Investigation of the third-order nonlinear susceptibility was done by femtosecond Z-scan technique and demonstrated the potential of phenyl-substituted allylidene malononitriles for its nonlinear optical applications. The observed positive lensing and strong reverse saturable absorption (RSA) at both visible (532 nm) and Near IR (800 nm) regions make this compound a promising candidate for optoelectronic applications.

Intriguing steroid glycosides for cancer therapy by suppressing the DNA damage response and mTOR/S6K signaling pathways

Two rare 8-hydroxysteroid glycosides (6–7), and their downstream metabolites (1–5) with an unprecedented 6/6/5/5/5-pentacyclic scaffold, together with seven known analogues (8–14) were isolated from the twigs and leaves of Strophanthus divaricatus. Their structures were fully assigned by analysis of the spectroscopic and ECD data, NMR calculations, X-ray crystallographic study, and chemical methods. In addition, the inhibitory effects of 1–14 on liver and lung cancer cell lines were evaluated, and preliminary structure–activity relationship was discussed. Data-independent acquisition (DIA)-based quantitative proteomic analysis and biological verification of H1299 cells suggested that this family of compounds may play an anticancer role by suppressing both DNA damage response (DDR) and mTOR/S6K signaling pathways.

D4-Symmetric Dirhodium Tetrakis(binaphthylphosphate) Catalysts for Enantioselective Functionalization of Unactivated C-H Bonds.

Dirhodium tetrakis(2,2'-binaphthylphosphate) catalysts were successfully developed for asymmetric C-H functionalization with trichloroethyl aryldiazoacetates as the carbene precursors. The 2,2'-binaphthylphosphate (BNP) ligands were modified by introduction of aryl and/or chloro functionality at the 4,4',6,6' positions. As the BNP ligands are C2-symmetric, the resulting dirhodium tetrakis(2,2'-binaphthylphosphate) complexes were expected to be D4-symmetric, but X-ray crystallographic and computational studies revealed this is not always the case because of internal T-shaped CH-π and aryl-aryl interactions between the ligands. The optimum catalyst is Rh2(S-megaBNP)4, with 3,5-di(tert-butyl)phenyl substituents at the 4,4' positions and chloro substituents at the 6,6' positions. This catalyst adopts a D4-symmetric arrangement and is ideally suited for site-selective C-H functionalization at unactivated tertiary sites with high levels of enantioselectivity, outperforming the best dirhodium tetracarboxylate catalyst developed for this reaction. The standard reactions were conducted with a catalyst loading of 1 mol % but lower catalyst loadings can be used if desired, as illustrated in the C-H functionalization of cyclohexane in 91% ee with 0.0025 mol % catalyst loading (29,400 turnover numbers). These studies further illustrate the effectiveness of donor/acceptor carbenes in site-selective intermolecular C-H functionalization and expand the toolbox of catalysts available for catalyst-controlled C-H functionalization.

Designing Dual-State and Aggregation-Induced Emissive Luminogens from Lignocellulosic Biosourced Molecules.

Utilizing lignocellulosic biosourced platforms, we synthesized novel cyanostilbene (CS) derivatives featuring the 3,4-dimethoxyphenyl moiety. These derivatives were investigated for their emission properties in both solution and solid states. The two simple CS derivatives exhibit very weak luminescence in solution but significant luminescence in the solid state, indicating distinct Aggregation-Induced Emission (AIE) characteristic. Furthermore, combining these two CS units, without conjugation and with quasi perpendicular orientation, results in a Dual-State Emission (DSE) fluorophore showing luminescence both in solution and solid states. X-ray crystallography studies on the solid-state compounds reveal a structure-emission relationship, demonstrating that the colour emission correlates with the conformations adopted by the molecules in the solid state, which influence the type of stacking.

Palladium(II) complexes of amino acid derived ONO-tridentate enamine ligand for Suzuki-Miyaura cross-coupling reaction

Three palladium(II) complexes with an ONO-tridentate enamine ligand were synthesized by reacting the glycine derivative ligand with palladium(II) acetate in the presence of selected ancillary ligands. The structures of the Pd(II) complexes were determined through melting point, C, H, N elemental analysis, ATR-FTIR, and NMR. Additionally, the molecular structures of two complexes were confirmed using single-crystal X-ray crystallography studies, revealing that the ligand coordinates to palladium(II) via ONO-chelation, resulting in a square planar geometry around the metal center. Catalytic activities of these compounds were assessed in the Suzuki-Miyaura cross-coupling reaction of phenylboronic acid with the different aryl halides.