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Copper complexes of 1-phenyl-1,3-butanedione have been synthesized, characterized and determined their molecular coordination geometry and examined their potent on ...methicillin-resistant Staphylococcus aureus (MRSA) validated by inhibition of electron transport chain and mechanism involved in membrane damage was confirmed by SEM.
•Diketone-copper(II) complexes were synthesized with different coordination number.•Complexes were characterized and their structures were confirmed by XRD method.•Complexes showed an excellent activity against methicillin-resistant St. aureus.•Complexes exhibit inhibition of electron transport and membrane damage.
The copper based metal complexes (CMC) were synthesized using 1-phenyl-1,3-butanedione with two different solvents, methanol and water:acetic acid. The X-ray structural analysis of the two CMCs indicates that, coordination environment around the complex 1 Cu(C10H10O2)2(CH4O) exhibits distorted square-pyramidal geometry with trans-isomer favored structure whereas complex 2 Cu(C10H10O2)2 exhibits distorted square-planar geometry with cis-isomer favored structure. Both copper complexes were characterized by SEM, EDX, Mass and TGA. Further, the CMCs were showed promising antibacterial activity by disc diffusion and minimum inhibitory concentration assay against Gram positive and Gram negative bacteria. The studied model showed CMC were potent against methicillin-resistant Staphylococcus aureus (MRSA) validated by inhibition of electron transport chain. The formation of membrane pore/damage by CMC leads to changes in the bioelectrochemistry of the MRSA was assessed and mechanism involved in membrane damage was confirmed by SEM. The study concludes that the complex 1 showed potent antibacterial action compared to standard drug ampicillin.
A novel mixed ligand Cu(II) complex, Cu2(C8H4O2SF3)2(C9H6NO)2, has been synthesized and characterized by FT-IR, UV–visible, SEM and EDAX techniques. A single crystal X-ray structure determination ...revealed the centrosymmetric dinuclear form of the Cu(II) complex and a distorted square pyramidal geometry around the Cu(II) centre. The Cu(II) complex exhibits various intermolecular interactions, leading to the construction of R22(16), R22(10) and R22(20) supramolecular synthons. The existence of intermolecular interactions is supported by Hirshfeld surface analysis and quantified by 2D fingerprint plots. In addition, the 3D topology of the molecular packing is visualized through energy frameworks, revealing the predominance of dispersion energy over other interaction energies. DFT calculations results well supported the experimental values. Further, the Cu(II) complex was evaluated against MRSA and these results were validated by molecular docking studies for penicillin-binding protein 2, with an excellent binding score of −8.0 kcal/mol.
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As an essential class of heterocyclic derivatives, 8-hydroxyquinoline(HQ) and 4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedione (TFTB) have a broad range of pharmaceutical applications and they are found to be excellent precursors for metal complexes and crystal engineering. The novel mixed ligand Cu(II) complex Cu2(C8H4O2SF3)2(C9H6NO)2 has been synthesized using a metal salt and the above ligands in a 1:1:1 M ratio and characterized by FT-IR, UV–visible, SEM and EDAX techniques. Single crystal X-ray structure analysis reveals a centrosymmetric dinuclear form of the Cu(II) complex, linked by the obtuse phenolate oxygen atom, and the central Cu(II) ion adopts a distorted square pyramidal coordination geometry. The Cu(II) complex exhibits various intermolecular interactions, leading to the construction of R22(16), R22(10) and R22(20) supramolecular synthons. The existence of intermolecular interactions is supported by Hirshfeld surface analysis and quantified by 2D fingerprint plots. In addition, the 3D topology of the molecular packing is visualized through energy frameworks, which reveal the predominance of dispersion energy over other interaction energies. DFT calculations have been performed for the mixed ligand Cu(II) complex to study the optimal geometry, related reactive parameters and the HOMO-LUMO energy gap (0.8232 eV). Further, the Cu(II) complex was evaluated against MRSA and showed an MIC value of 15 μg/mL. A time-killing assay for the Cu(II) complex was performed to study the antimicrobial effect with respect to time. A molecular docking study revealed the binding affinity of the Cu(II) complex to penicillin-binding protein 2, with an excellent binding score of −8.0 kcal/mol.
Nonstandard nucleotide triphosphate pyrophosphatase (NTPase) can efficiently hydrolyze nonstandard purine nucleotides in the presence of divalent cations. The crystal structures of the NTPase from
...Pyrococcus horikoshii OT3 (
PhNTPase) have been determined in two unliganded forms and in three liganded forms with inosine 5′-monophosphate (IMP), ITP and Mn
2+, which visualize the recognition of these ligands unambiguously. The overall structure of
PhNTPase is similar to that of previously reported crystal structures of the NTPase from
Methanococcus jannaschii and the human ITPase. They share a similar protomer folding with two domains and a similar homodimeric quaternary structure. The dimeric interface of NTPase is well conserved, and the dimeric state might be important to constitute the active site of this enzyme. A conformational analysis of the five snapshots of
PhNTPase structures using the multiple superposition method reveals that IMP, ITP and Mn
2+ bind to the active site without inducing large local conformational changes, indicating that a combination of interdomain and interprotomer rigid-body shifts mainly describes the conformational change of
PhNTPase. The interdomain and interprotomer conformations of the ITP liganded form are essentially the same as those observed in the unliganded form 1, indicating that ITP binding to
PhNTPase in solution may follow the selection mode in which ITP binds to the subunit that happens to be in the conformation observed in the unliganded form 1. In contrast to the human ITPase inducing a large domain closure upon ITP binding, the interdomain active site cleft is generally closed in
PhNTPase and only the IMP binding form shows a remarkable domain opening by 14° only in the B subunit. The interprotomer rigid-body rotation of
PhNTPase has a tendency to keep the dimeric 2-fold symmetry, which is also true in human ITPase, thereby suggesting its relevance to the positive cooperativity of the dimeric NTPases. The exception of this rule is observed in the IMP liganded form in which the dimeric 2-fold symmetry is broken by a 3° interprotomer rotation in an unusual direction. A combination of the exceptional interdomain and interprotomer relocations is most likely the reason for the observed asymmetric IMP binding that might be necessary for
PhNTPase to release the reaction product IMP.
SL ligand (E)‐2‐(((2‐(tert‐butylthio) phenyl) imino)methyl)‐4‐chlorophenol) and its Cu(II) complex Cu(C14H12ClNOS)2 are synthesized and characterized by FTIR, SEM, EDX and TGA. Single crystal X‐ray ...diffraction studies revealed that the ligand and Cu(II) complex crystallizes in identical space group and the copper complex exhibits square planar geometry (τ4=0). SL and copper complex show C−Cl⋯π and C−H⋯π interaction respectively enables the formation of multi‐dimensional supramolecular architecture and its nature of interactions is quantified by Hirshfeld surface analysis. The strength of the interaction and 3D topology of crystal packing are visualized through an energy framework. Further, the physical nature of intramolecular interactions is assessed by QTAIM and NCI index model. DFT was employed to evaluate the optimized electronic structure, HOMO‐LUMO, energy gap, molecular properties and global parameters. The copper complex exhibited good antibacterial activity against the S.aureus and MRSA and compared with the standard drug (gentamicin). The molecular docking studies of the copper complex show a high affinity towards penicillin‐binding protein 2 and topoisomerase II DNA gyrase.
trans N−O Cu(II) complex is compared with symmetric compartmental ligand and structurally characterized by single‐crystal X‐ray diffraction. The energetic difference of non‐covalent interactions are assed by quantum computational studies.
Abstract
SL ligand
(E)‐2‐(((2‐(tert‐butylthio) phenyl) imino)methyl)‐4‐chlorophenol)
and its Cu(II) complex Cu(C
14
H
12
ClNOS)
2
are synthesized and characterized by FTIR, SEM, EDX and TGA. ...Single crystal X‐ray diffraction studies revealed that the ligand and Cu(II) complex crystallizes in identical space group and the copper complex exhibits square planar geometry (τ
4
=0). SL and copper complex show C−Cl⋯π and C−H⋯π interaction respectively enables the formation of multi‐dimensional supramolecular architecture and its nature of interactions is quantified by Hirshfeld surface analysis. The strength of the interaction and 3D topology of crystal packing are visualized through an energy framework. Further, the physical nature of intramolecular interactions is assessed by QTAIM and NCI index model. DFT was employed to evaluate the optimized electronic structure, HOMO‐LUMO, energy gap, molecular properties and global parameters. The copper complex exhibited good antibacterial activity against the
S.aureus
and
MRSA
and compared with the standard drug (gentamicin). The molecular docking studies of the copper complex show a high affinity towards penicillin‐binding protein 2 and topoisomerase II DNA gyrase.
2‐Keto‐3‐deoxygluconate (KDG) is one of the important intermediates in pectin metabolism. An enzyme involved in this pathway, 3‐dehydro‐3‐deoxy‐D‐gluconate 5‐dehydrogenase (DDGDH), has been ...identified which converts 2,5‐diketo‐3‐deoxygluconate to KDG. The enzyme is a member of the short‐chain dehydrogenase (SDR) family. To gain insight into the function of this enzyme at the molecular level, the first crystal structure of DDGDH from Thermus thermophilus HB8 has been determined in the apo form, as well as in complexes with the cofactor and with citrate, by X‐ray diffraction methods. The crystal structures reveal a tight tetrameric oligomerization. The secondary‐structural elements and catalytically important residues of the enzyme were highly conserved amongst the proteins of the NAD(P)‐dependent SDR family. The DDGDH protomer contains a dinucleotide‐binding fold which binds the coenzyme NAD+ in an intersubunit cleft; hence, the observed oligomeric state might be important for the catalytic function. This enzyme prefers NAD(H) rather than NADP(H) as the physiological cofactor. A structural comparison of DDGDH with mouse lung carbonyl reductase suggests that a significant difference in the α–loop–α region of this enzyme is associated with the coenzyme specificity. The structural data allow a detailed understanding of the functional role of the conserved catalytic triad (Ser129–Tyr144–Lys148) in cofactor and substrate recognition, thus providing substantial insights into DDGDH catalysis. From analysis of the three‐dimensional structure, intersubunit hydrophobic interactions were found to be important for enzyme oligomerization and thermostability.
ATP‐binding cassette (ABC) transporters, also known as traffic ATPases, form a large family of integral membrane proteins responsible for the translocation of a variety of chemically diverse ...substrates across the lipid bilayers of cellular membranes of both prokaryotes and eukaryotes by the hydrolysis of ATP. The ATP‐binding subunit of an ABC transporter from Geobacillus kaustophilus, a homodimeric enzyme, was overexpressed in Escherichia coli and purified. Crystals were obtained using the microbatch‐under‐oil method at 291 K. X‐ray diffraction data to 1.6 Å resolution were collected on SPring‐8 beamline BL26B1. The crystals belonged to the orthorhombic space group I222, with unit‐cell parameters a = 54.94, b = 78.63, c = 112.96 Å. Assuming the presence of a dimer in the asymmetric unit gave a crystal volume per protein weight (VM) of 2.32 Å3 Da−1 and a solvent content of 47%; this was consistent with the results of a dynamic light‐scattering experiment, which showed a dimeric state of the protein in solution. Molecular‐replacement trials using the crystal structure of HisP from the Salmonella typhimurium ATP‐binding subunit of an ABC transporter as a search model did not provide a satisfactory solution, indicating that the two ATP‐binding subunits of ABC transporters have substantially different structures.
A putative UDP‐N‐acetyl‐d‐mannosamine dehydrogenase from Pyrococcus horikoshii OT3, an essential enzyme for polysaccharide biosynthesis, has been overexpressed in Escherichia coli and purified. ...Crystals were obtained using the oil‐microbatch method at 291 K. A native data set extending to 1.8 Å resolution has been collected and processed in space group P21. Assuming the presence of a dimer in the asymmetric unit, the VM value is calculated to be 2.3 Å3 Da−1, which is consistent with the result of a dynamic light‐scattering experiment that shows a dimeric state of the protein in solution.
The compounds, 5-methyl-5H-dibenzob,fazepine (1) and 5-(4-methylbenzyl)-5H-dibenzob,fazepine (2), were synthesized and characterized by spectral studies, and finally confirmed by single crystal X-ray ...diffraction method. The compound 1 crystallizes in the orthorhombic crystal system in Pca21 space group, having cell parameters a=11.5681 (18) Å, b=11.8958 (18) Å, c=8.0342 (13) Å, and Z=4 and V=1105.6 (3) Å3. And the compound 2 crystallizes in the orthorhombic crystal system and space group Pbca, with cell parameters a=16.5858 (5) Å, b=8.4947 (2) Å, c=23.1733 (7) Å, and Z=8 and V=3264.92 (16) Å3. The azepine ring of both molecules 1 and 2 adopts boat conformation with nitrogen atom showing maximum deviations of 0.483 (2) Å and 0.5025 (10) Å, respectively. The C–H⋯π short contacts were observed. The dihedral angle between fused benzene rings to the azepine motif is 47.1 (2)° for compound 1 and 52.59 (6)° for compound 2, respectively. The short contacts were analyzed and Hirshfeld surfaces computational method for both molecules revealed that the major contribution is from C⋯H and H⋯H intercontacts.
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