A new Sm4 compound constructed by an 8-hydroxyquinoline Schiff base ligand: Synthesis, crystal structure and DNA interaction

Synthesis, structure elucidation and surface analysis of a new single crystal N-((2-(benzo [4,5]imidazo [1,2-c]quinazolin-6-yl)phenyl)carbamothioyl)heptanamide: Theoretical and experimental DNA binding studies

Synthesis, spectral characterization, crystal structures, biological activities, theoretical calculations and substitution effect of salicylidene ligand on the nature of mono and dinuclear Zn(II) Schiff base complexes

Supramolecular self-assembly, DNA interaction, antibacterial and cell viability studies of Cu(II) and Ni(II) complexes derived from NNN donor Schiff base ligand

Mono- and trinuclear copper(II) complexes with 2-[1-(2-dimethylamino-ethylamino)-ethyl]-phenol (HL) have been synthesized and structurally characterized. The mononuclear complex [Cu(L)(H2O)(ONO2)] (1) crystallizes in monoclinic space group P21 /n with a square pyramidal Cu(II) center coordinated by the tridentate Schiff base (L) and a water ligand in the equatorial plane and an oxygen atom from nitrate in the axial position. The trinuclear complex [(CuL)3(μ3-OH)](ClO4)2·H2O (2) crystallizes in hexagonal space group P63; all three copper atoms are five-coordinate with square pyramidal geometries. The interactions of these complexes with calf-thymus DNA have been investigated using absorption spectrophotometry. The mononuclear complex binds more strongly than the trinuclear complex. The DNA cleavage activity of these complexes has been studied on double-stranded pBR 322 plasmid DNA by gel electrophoresis experiments in the absence and in the presence of added oxidant (H2O2). The trinuclear complex cleaves DNA more efficiently than the mononuclear complex in the presence of H2O2.

Three hydrazone ligands, H2L1-H2L3, made from salicylaldehyde and ibuprofen- or naproxen-derived hydrazides, were prepared and transformed into the corresponding copper(II) complexes [Cu(II)L1] x H2O, [Cu(II)L2], and [(Cu(II))2(L3)2] x H2O x DMF (Scheme). The X-ray crystal structure of the last-mentioned complex was solved (Fig. 1), showing a square-planar complexation geometry, and the single units were found to form a one-dimensional chain structure (Fig. 2). The interactions of these complexes with CT-DNA were studied by different techniques, indicating that they all bind to DNA by classical and/or non-classical intercalation modes.

Synthesis of derived Cu(II) complex from Schiff base of Vitamin B6 and antihypertensive hydralazine: DNA interaction, biological application and molecular docking studies

This article presents a new and facile method for the synthesis of Schiff base compounds with a benzimidazole group using a low-cost and reusable calcium aluminate nanophosphorus catalyst (CaAl2O4). This approach avoids harmful solvents and reactants, supporting a more environmentally friendly synthesis process. The catalyst maintained its activity and heterogeneity over four cycles with minimal loss of efficiency. The synthesis process was straightforward and eliminated the need for column chromatography. The Schiff base ligand (HL=(E)-N-((6-(thiophen-2-yl)pyridin-2-yl)methylene)-1H-benzo[d]imidazol-2-amine)) was synthesized by the reaction of 6-(thiophen-2-yl)pyridine-2-carbaldehyde with 1H-benzimidazole-2-amine. Subsequently, metal(II) complexes of Co(II), Ni(II), and Cu(II) were prepared using this ligand. Structural analysis of both the ligand and its metal complexes was carried out using various physicochemical and spectroscopic methods. Ni(II) and Co(II) complexes were found to adopt an octahedral geometry, while the Cu(II) complex exhibited a square-planar structure. Binding studies with calf thymus DNA (CT-DNA) at pH 7.2 were performed using UV-visible spectroscopy, viscosity measurements, and thermal denaturation studies and showed that the metal complexes intercalate into the DNA and produced a distinct binding pattern. Molecular docking simulations with AutoDock Vina provided insights into the interaction of these complexes with the B-DNA dodecamer. Furthermore, the ligand and its metal complexes showed UV-visible photonuclease activity against pUC19 DNA. Agarose gel electrophoresis showed that the metal complexes exhibit photoinduced nuclease activity, confirming their ability to cleave DNA upon exposure to light.

In the present work, 2‐hydroxy‐1‐naphthaldhyde and 2‐hydrazino‐N‐phenyl‐2‐thioxo‐acetamide are combined to create a new Schiff base. The novel ligand and its six new binuclear complexes with Ni(II), Cu(II), Ag(I), Zn(II), Cd(II), and La(III) are characterized via spectroscopic and analytical techniques, such as ultraviolet‐visible (UV–vis), infrared (IR), 1H NMR, 13C NMR, mass spectra, powder X‐ray diffraction (XRD), and thermogravimetric (TG) analysis. The spectral analysis indicated that the novel Schiff base may coordinate with the two metal ions. Additionally, the results indicated a square planar geometry for NiL, CuL, and AgL complexes and an octahedral geometry for ZnL, CdL, and LaL complexes. In contrast to the Schiff base ligand, different complex crystallinities were displayed in the powder XRD patterns. Significant thermodynamic parameter values were computed using the Coats–Redfern method which revealed high thermal stabilities of the complexes in the TG analysis. In vitro antibacterial, DNA‐binding, and anti‐inflammatory techniques were used for the biological evaluation. Moreover, to visualize the anti‐inflammatory action of complexes employing the cyclooxygenase enzyme receptor (PDB ID: 6COX), in silico docking was used. The serial dilution method evaluated the new compounds' in vitro antibacterial efficacy against three bacterial and one fungal strain. The results showed that the novel complexes showed remarkable efficiency against the bacterial growth of gram (+ve) Staphylococcus aureus compared to the parent ligand and the control. On the other hand, the ZnL, CdL, and AgL complexes showed excellent bactericidal activity. The inhibition of protein denaturation followed the following sequence: Ibuprofen > ZnL ˃ NiL ˃ AgL ˃ CuL > CdL > LaL > H2L. UV–visible and gel electrophoresis methods were used to examine the metal complexes and their ligand's affinity for binding DNA. An intercalative binding mechanism was suggested by the findings.

A novel heterometallic [CoII2CoIII4CeIV] cluster formed by In Situ reaction: Crystal structure, DNA interaction and efficient conversion of CO2 into cyclic carbonates

NKX2.5 is a homeodomain (HD) containing transcription factor preferentially expressed in cardiomyocytes. Mutations in the NKX2.5 gene have been identified in patients with congenital heart disease, suggesting its critical roles in cardiac development and maturation. NKX2.5 is reported to regulate transcription of atrial natriuretic factor (ANF), potentially through direct binding to -242 bp proximal promoter region (ANF-242). ANF-242 contains two palidromic NKX2.5 binding sites, and occupation of both sites by NKX2.5 has been reported. In addition, physical interaction between NKX2.5 proteins has been suggested to facilitate DNA binding through domains outside of the HD. However, detailed crystal structure of NKX2.5 protein is currently not available. The HD of human NKX2.5 (aa 138–197; C193S) with the oxidizable Cys193 substituted with Ser was co-crystallized with 19bp double stranded DNA including ANF-242 region. This mutant was reported to have the same DNA binding characteristics as the wild type. The crystal structure was determined at 1.8 Å resolution with final R-working and R-free values of 0.234 and 0.278, respectively. Consistent with previous studies, two molecules of NKX2.5 HD are bound to ANF-242 region without physical interaction between the two proteins. Column purification demonstrated that NKX2.5 behaves as dimers in solution in a concentration dependent manner. These results suggest that dimeric NKX2.5 HD in solution may change conformation upon DNA binding. Among various NK class proteins, the three-dimensional structure has only been determined in the HD of Drosophila vnd/NK2 (ventral nervous system defective proteins) using NMR. When the two HDs are compared, NKX2.5 HD shows extended DNA contacts to a total of 8 base pairs. Most of the residues of HD implicated in pathology of mutants are involved in DNA binding and structural stabilization. The structure of NKX2.5 HD with ANF-242 shows that the HD occupies two binding sites of ANF-242 without physical interaction between themselves. This high resolution crystal structure of NKX2.5 protein provides a detailed picture of protein and DNA interactions, which allows us to predict DNA binding of mutants identified in human patients. This research has received full or partial funding support from the American Heart Association, AHA Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).

Four Pd(II) complexes of general formula [Pd(L1)2(L2)2], where L1 = pyridine-2(1H)-thione, pyrimidine-2(1H)-thione, pyridine-4(1H)-thione, and pyridine-4(1H)-thione, L2 = tri-p-tolylphosphine, have been synthesized by direct reaction of K2[PdCl4] with phosphine and heterocyclic thiones ligands in 1 : 2 : 2 molar ratio. The complexes have been characterized by elemental analyses, FT-IR and multinuclear NMR spectroscopy. The complexes 1 and 2 were also characterized by single crystal X-ray diffraction which revealed that the Pd(II) atom adopted a nearly square planar geometry with two tri-p-tolyphosphine molecules bound in a trans fashion and also two pyridine-2(1H)-thione (1) or pyrimidine-2(1H)-thione (2) molecules trans to each other. The compounds were tested for antibacterial activity, DNA interaction by brine shrimp lethality bioassay, antitumor activity, and gel electrophoresis. The complexes demonstrated moderate activity against gram positive and gram negative bacterial strains in comparison with a standard drug imipenum. Their antitumor activity against MCF7 tumor cell line was determined to be comparable to that of doxorubicin. The investigated compounds demonstrated no cytotoxic effect in brine shrimp bioassay study.

NKX2.5 is a homeodomain containing transcription factor regulating cardiac formation and function, and its mutations are linked to congenital heart disease. Here we provide the first report of the crystal structure of the NKX2.5 homeodomain in complex with double-stranded DNA of its endogenous target, locating within the proximal promoter -242 site of the atrial natriuretic factor gene. The crystal structure, determined at 1.8 Å resolution, demonstrates that NKX2.5 homeodomains occupy both DNA binding sites separated by five nucleotides without physical interaction between themselves. The two homeodomains show identical conformation despite the differences in the DNA sequences they bind, and no significant bending of the DNA was observed. Tyr54, absolutely conserved in NK2 family proteins, mediates sequence-specific interaction with the TAAG motif. This high resolution crystal structure of NKX2.5 protein provides a detailed picture of protein and DNA interactions, which allows us to predict DNA binding of mutants identified in human patients.

Synthesis of cadmium(II) complexes with polyamines: Crystal structure, theoretical calculation, photocatalytic, DNA interaction and biological studies

Synthesis, crystal structure, DNA interaction and antioxidant activities of two novel water-soluble Cu(2+) complexes derivated from 2-oxo-quinoline-3-carbaldehyde Schiff-bases

FOXO transcription factors are a subgroup of the FOX (forkhead) family and are important for regulation of cellular processes, gene expression, apoptosis, cell‐ cycle progression, and oxidative stress resistance. Several FOXO translocations have also been implicated in cancer development, with the most common being the PAX3‐FOXO1 translocation linked to the development of Alveolar Rhabdomyosarcoma (ARMS). All FOXO proteins share sequence similarity and a highly conserved DNA‐ binding domain (DBD). This DNA‐binding domain consists of three alpha helices accompanied by two winged domains; this domain binds the Daf‐16 binding element (DBE) and the insulin response element (IRE), with the crystal structure indicating that the majority of the DNA contacts are located within Helix 3. There have been reports in the literature of sequences flanking the IRE causing an increase in binding affinity; however, no mechanism has been reported to explain this effect. Using Molecular Dynamics Simulation (MDS) we observed that the number of direct interactions between protein and DNA increases over time. Interestingly, MDS showed that wing 1 has no contact with DNA at 0 ns but eventually makes contact with a region flanking the IRE consensus sequence at 10 ns. In order to verify the new interactions observed in the 10 ns model, we mutated several bases within the IRE and observed the effect of these mutations on the interaction between protein and DNA through Electrophoretic Mobility Shift Assays (EMSA) and intrinsic fluorescence. Mutation of several bases in the IRE consensus sequence as well as in the immediate 5′ and 3′ flanking regions decreased the interaction between FOXO1 and DNA. In support of our model, mutation of the new base contact identified with Wing 1 also decreased FOXO1 DNA‐binding. The truncated FOXO1 DNA‐binding domain found in the PAX3‐FOXO1 fusion was also examined by MDS, and was predicted to retain several contacts within Helix 3 as well as the newly identified contact in Wing 1. Using this information, we can further examine the DNA‐binding of PAX3‐FOXO1 to determine if the presence of flanking sequences surrounding the IRE consensus sequence also affect the affinity of the fusion protein for DNA. Knowledge of the contribution of the FOXO1 domain to PAX3‐FOXO1 DNA targeting is important for understanding the activity of this fusion protein and its role in ARMS development.Support or Funding InformationNIH SC2GM095430RCMI‐Molecular Structure and Modeling core facility (NIH‐RCMI 2G12MD007595‐06 )NIH 5RL5GM118966‐03RISE (R25GM060926)