Presence Of Complexes Research Articles

Phosphorylation-induced flexibility of proto-oncogenic Bcl3 regulates transcriptional activation by NF-κB p52 homodimer.

B cell lymphoma 3 (Bcl3), a member of the IκB family proteins, modulates transcription by primarily associating with NF-κB p50 and p52 homodimers. Bcl3 undergoes extensive phosphorylation, though the functions of many of these modifications remain unclear. We previously described that phosphorylation at Ser33, Ser114 and Ser446 partially switches Bcl3 from acting as an IκB-like inhibitor to a transcription regulator by associating with the (p52:p52):DNA binary complex. Here, we identified another critical phosphorylation site, Ser366. Substituting at all four residues to phospho-mimetic glutamate further enhances Bcl3's transcriptional activity. Phospho-modifications retain Bcl3's ability to stably bind p52 but induces reciprocal structural changes as revealed by HDX-MS experiments; the N-terminal region stiffens, while the C-terminus becomes more flexible. The increased flexibility allowed the Bcl3:(p52p52) binary complex to better accommodate DNA. The removal of the C-terminal 28-residues transformed Bcl3 into a transcriptional activator independent of phosphorylation. Notably, most identified mutations in Bcl3 from various cancers map to its C-terminus, suggesting the functional relevance of Bcl3 C-terminal structural flexibility and enhanced interaction with (p52p52):DNA complex to transcriptional potential and disease. Overall, this study uncovers the mechanistic basis by which phosphorylation-driven structural changes convert Bcl3 from an inhibitor to a transcriptional cofactor of NF-κB, and how deregulation of its activity through altered phosphorylation or mutation can lead to cancer.

Insights into lipid-modified recognition of Apolipoprotein E3 to extra-cellular domain of TREM2 associated with Alzheimer’s disease

E3 genotype of apolipoprotein E (ApoE) and triggering receptor expressed on myeloid cells 2 (TREM2) are critical genetic risk factors for late-onset Alzheimer’s diseases (AD) that influences the formation of plaques and neurofibrillary tangles associated with AD pathogenesis. In addition, variation in genetic association of ApoE and TREM2 in presence of lipids have been advocated to potentially regulate different aspects of AD pathology by facilitating the clearance of amyloid beta (Aβ) from brain. However, the proteinopathy and functional mechanism underlying their molecular interaction in presence of lipid remains poorly understood. Herein, to shed inherent insights into the mode of ApoE3-TREM2 interaction in both lipid and aqueous medium, we have used a combination of different state-of-the-art computational tools including knowledge-based protein–protein docking and molecular dynamics (MD) simulations. Remarkably, we find the direct involvement of regulatory complementarity-determining region-2 (CDR2) loop of TREM2 in interaction with the major hinge region and helix H4 of ApoE3. We further anticipate that ApoE3 attains distinct conformational states and forms an open and extended cavity-like structure in ApoE3-TREM2 complex in presence of lipids. Our data also exhibits reduced hydrophobicity in the ApoE3 binding interface of TREM2, which sets a baseline for reduced binding affinity towards ApoE3. Therefore, we hypothesize that this decline in hydrophobic index might have resulted due to structural variations in the H4 helix and major hinge region leading to altered TREM2 conformation in presence of lipids. Altogether, our findings demonstrate the effect of phospholipids on the structural dynamics and conformation of ApoE3, which contributes to our understanding of how APOE and TREM2 influences the development of AD. However, further experimental studies are necessary to validate and explore our findings which will open up new avenues towards development of novel therapeutic strategies for AD.

Colloidal Stability of Chitosan/DNA Polyelectrolyte Complexes in Presence of Biological Polyanions

AbstractNatural or synthetic polycations are used in nucleic acid‐based therapies as complexing agents which interact electrostatically with nucleic acids, condense them into nanoparticles, protect them and control their entry into cells. However, although the literature on the formation of nanoparticles known as complexes is well documented, fewer studies have focused on the physical chemistry behind their disassembly, especially under physicochemical conditions found in an intracellular environment. There are several theories of the disassembly of these complexes, one of them consisting in the exchange between the polycations of these particles with biological polyanions. This project is focused on the study of the complexation mechanism of chitosan and calf‐thymus DNA, as well as the stability of the obtained complexes in presence of biological polyanions, i.e., glycosaminoglycans (GAGs). In the presence of polyelectrolyte complexes, GAGs that are present in cells are expected to compete with nucleic acids and dissociate the complex if polycation–GAG association is thermodynamically favored. It is found that chitosan/DNA complexes colloidal stability depends on its [N+]/[P−] charge ratio (R). Furthermore, it is determined that the aggregation onset of the complexes, generated by the addition of different GAGs, depends on the structure and the charge density of the GAGs.

Multi-channel anion sensing behaviour of a Ru(II)-bipyridine complex based on benzothiazolyl pyrazole ligand: Experimental and implication of machine learning tools for data prediction

Multi-channel anion sensing characteristics of a Ru(II) complex of the form [(bpy)2Ru (Hpzbzth)](ClO4)2 (1) {bpy = 2,2′-bipyridine and Hpzbzth = 3,5-bis(benzthiazol-2-yl)pyrazole} has been carried out in this work and analyzed through multiple machine learning tools. The complex possesses one pyrazole NH proton in its outer sphere which upon interaction with specific anions yields considerable change in its photo-redox behaviours. The anion sensing aspect of the complex is systematically investigated in acetonitrile through absorption, steady state and time-resolved emission spectroscopy as well as by square-wave (SWV) voltammetry. In absence of anions, the complex displays emission and represents the “on-state”, while complete quenching of emission takes place in presence of basic anions and designates the “off-state” of the system. The initial state of the complex could also be restored upon addition of acid and the process is reversible. Essentially, the complex acts as anion- and acid-induced molecular switches. The absorption, emission and electrochemical outputs of the complex in presence of anions and acid are employed to mimic different types of Boolean and Fuzzy logic (FL) functions. Additionally, we implemented herein different deep learning tools such as artificial neural networks (ANNs) and adaptive neuro-fuzzy inference system (ANFIS) to envisage the full anion sensing aspects of the complex. The outcomes of the three models are compared and also tallied with the experimental results.

Bonding and Reactivity in Terminal versus Bridging Arenide Complexes of Thorium Acting as ThII Synthons

AbstractThorium redox chemistry is extremely scarce due to the high stability of ThIV. Here we report two unique examples of thorium arenide complexes prepared by reduction of a ThIV‐siloxide complex in presence of naphthalene, the mononuclear arenide complex [K(OSi(OtBu)3)3Th(η6‐C10H8)] (1) and the inverse‐sandwich complex [K(OSi(OtBu)3)3Th]2(μ‐η6,η6‐C10H8)] (2). The electrons stored in these complexes allow the reduction of a broad range of substrates (N2O, AdN3, CO2, HBBN). Higher reactivity was found for the complex 1 which reacts with the diazoolefin IDipp=CN2 to yield the unexpected ThIV amidoalkynyl complex 5 via a terminal N‐heterocyclic vinylidene intermediate. This work showed that arenides can act as convenient redox‐active ligands for implementing thorium‐ligand cooperative multielectron transfer and that the reactivity can be tuned by the arenide binding mode.

Bonding and Reactivity in Terminal versus Bridging Arenide Complexes of Thorium Acting as ThII Synthons.

Thorium redox chemistry is extremely scarce due to the high stability of ThIV . Here we report two unique examples of thorium arenide complexes prepared by reduction of a ThIV -siloxide complex in presence of naphthalene, the mononuclear arenide complex [K(OSi(Ot Bu)3 )3 Th(η6 -C10 H8 )] (1) and the inverse-sandwich complex [K(OSi(Ot Bu)3 )3 Th]2 (μ-η6 ,η6 -C10 H8 )] (2). The electrons stored in these complexes allow the reduction of a broad range of substrates (N2 O, AdN3 , CO2 , HBBN). Higher reactivity was found for the complex 1 which reacts with the diazoolefin IDipp=CN2 to yield the unexpected ThIV amidoalkynyl complex 5 via a terminal N-heterocyclic vinylidene intermediate. This work showed that arenides can act as convenient redox-active ligands for implementing thorium-ligand cooperative multielectron transfer and that the reactivity can be tuned by the arenide binding mode.

TolC-AcrA complex formation monitored by time dependent single-channel electrophysiology

Characterizing protein-protein interaction on a single molecular level is a challenge, experimentally as well as interpretation of the data. For example, Gram-negative bacteria contain protein complexes spanning the outer and inner cell wall devoted to efflux effectively cell toxic substances. Recent seminal work revealed the high-resolution structure of such a tripartic composition TolC-AcrA-AcrB suggesting to design inhibitors preventing efflux of antibiotics. To show that electrophysiology can provide supporting information here, we reconstitute single TolC homotrimer into a planar lipid membrane, apply a transmembrane voltage and follow the assembly of AcrA to TolC using the modulation of the ion current through TolC channel during binding. In particular, the presence of AcrA in solution increases the average ionic current through TolC and, moreover, reduces the ion-current fluctuations caused by flickering of TolC. Here, we show that statistical properties of ion-current fluctuations (the power spectral density) provide a complementary measure of the interaction of the TolC-AcrA complex in presence of putative efflux pump inhibitors. Both characteristics, the average ion current across TolC and the current noise, taken into consideration together, point to a stiffening of the tip of TolC which might reduce the formation of the complex.

NEW SIMPLE METHOD FOR THE DETERMINATION OF TRACE LEVEL COPPER (II) USING 1- [2- (ALLYLAMINO) -1-METHYLETHYL] THIOUREA IN PRESENCE OF HYDROFOB AMINES BY MOLECULAR ABSORPTION SPECTRAL METHOD IN THE UV AND VISIBLE REGION

Cu(II) with 1- [2- (allylamino) -1-methylethyl] thiourea the rapid reacts to form orange complex and also it to form to form brownish complexes in presence of the phenanthroline (Phen) and α,α′ - dipyridine ( α,α′ -dip ). The absorption spectra of the Cu(II) - AMTIC system is a curve with the maximum absorbance at 415 nm and molar absorption coefficient of 1.95.104 l mol−1 cm−1. The absorption spectra of the Cu(II)- AMTIC- Phen and Cu(II) -AMTIC - α,α′-dip systems is a curve with the maximum absorbances at 437 nm and 443 nm and molar absorption coefficients of 2.94.104 l mol−1 cm−1 and 2.81.104 l mol−1 cm−1, respectively. The absorbance was linear for 0.25–2.07 mkg ml−1 of Cu(II) in the Cu(II)- AMTIC system and 0.12 –2.56 mkg ml−1 and 0.18–2.45 mkg ml−1 of Cu(II) in the Cu(II)-AMTIC- Phen and Cu(II)-AMTIC- α,α′-dipsystems, respectively. The proposed methods was successfully used in the determination of Cu(II) in several synthetic mixtures. The relative standard deviation (n = 5) was 0%–2.0%, for Cu(II), indicating that this methods are highly precise and reproducible. The results obtained agree well with synthetic mixture samples analyzed by inductively coupled plasma optical emission spectrometry (ICP-OES). Keywords: copper, 1- [2- (allylamino) -1-methylethyl] thiocarbamide, phenanthroline (Phen ) and α,α′ - dipyridine.

‘On and Off’ intercalative binding behaviour of double chain surfactant cobalt(III) complex containing 2, 2′-bipyridyl ligand in β-Cyclodextrin: A detail approach on Host-guest inclusion of surfactant cobalt(III) complex and CT-DNA binding in micro-heterogeneous medium

The binding interaction of surfactant cobalt(III) complex, cis-[Co(bpy)2(HA)2](ClO4)3, in which bpy is 2,2-bipyridine and HA is hexadecylamine or cetylamnine with DNA was through intercalative mode via the long aliphatic chains present in the ligands. The binding was investigated by various techniques, electronic absorption, fluorescence spectroscopy, circular dichroism (CD), cyclic voltametry (CV) and viscosimetry measurements. The spectroscopic studies together with cyclic voltammetry and viscosity experiments support that the surfactant cobalt(III) complex binds to calf thymus DNA by intercalation through the aliphatic chain present in the complex into the base pairs of DNA. The presence of bipyridine ligand with larger π-frame work may also enhance intercalation. UV–vis., spectrum showed 4 nm bathochromic shift of the absorption band at 352 nm along with significant hypochromicity for the absorption band of the complex. The intrinsic binding constants(at below and above CMC are Kb = 2.41 × 105M−1, Kb = 3.12 × 106M−1 respectively) is more in keeping with intercalators and suggests this binding mode. The viscosity measurements showed that the surfactant cobalt(III) complex-DNA interaction can be hydrophobic and confirm intercalation. Moreover, the complex induced detectable changes in the CD spectrum of CT-DNA. Competitive binding study with ethidium bromide (EB) shows that the surfactant complex exhibits the ability to displace the DNA-bound EB indicating that the complex binds to DNA in strong competition with EB for the intercalative binding site. Also, CV results confirm this mode because, with increasing the CT-DNA concentration, shift to higher potential was observed. Besides the effect of binding of surfactant cobalt(III) complex to DNA in presence of β-cyclodextrin has also studied. This binding of the surfactant cobalt(III) complex in presence of β-cyclodextrin medium has been prevented (at below and above CMC are Kb = 5.45 × 104M−1, Kb = 6.92 × 105M−1 respectively) due to the incorporation of the aliphatic chains into the cavity of β-cyclodextrin. In presence of β-cyclodextrin the binding occur through surface and (or) groove binding can be attributed to the inclusion of the long aliphatic chain that is present in one of the ligands into cyclodextrin.

Highly Selective Rhodium Catalyzed 1,4‐Hydrogenation of Conjugated Dienals

AbstractThe combination of a large bite‐angle diphosphine with a neutral rhodium complex in presence of a weak base has enabled the regio‐ and chemoselective hydrogenation of the α,β‐carbon‐carbon double bond of conjugated dienals in high selective fashion. This methodology offers a mild and neutral alternative to the commonly employed Claisen rearrangement in the synthesis of γ,δ‐unsaturated aldehydes. A large variety of substituted α,β,γ,δ‐bis‐unsaturated aldehydes has been selectively hydrogenated with the catalyst described herein showing the potential of this new methodology.

CTK7A, a curcumin derivative, can be a potential candidate for targeting HIF-1α/p300 complex: Evidences from in vitro and computational studies

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor which plays a critical role in several biochemical pathways, and consists of oxygen-dependent alpha (α) and a constitutively expressed beta (β) subunit. Under hypoxic conditions, HIF-1α is stabilized and forms a complex with β subunit and this complex is associated with cancer progression. HIF-1α activity is mainly regulated by its transcriptional co-activator p300 which has histone acetyl-transferase (HAT) activity. p300 HAT activity is very crucial for p300 auto-acetylation and subsequently its interaction with its partner molecule HIF-1α as well as proapoptotic protein p53. p300 is a multi-domain protein and CH1 domain of p300 is the interacting partner of the C-terminal domain (CTD) of HIF-1α as well as p53. Several p300 HAT inhibitors are reported to suppress p300 auto-acetylation which inhibits its interaction with associated partners. We demonstrated that the p300 HAT inhibitor CTK7A down-regulated p300 auto-acetylation, HIF-1α accumulation as well as activity in gastric cancer cell lines. Protein-protein interaction and molecular docking studies revealed a significant decrease in the binding energy of full-length p300 as well as p300-CH1 and HIF-1α-CTD complex in presence of CTK7A. Further, SwissADME, evaluates the drug-likeliness property of CTK7A by analyzing its lipophilicity, size, polarity, solubility, saturation, and flexibility. Our in vitro and in silico data support reduced HIF-1α-p300 interaction in the presence of CTK7A. Hence, CTK7A might be playing a crucial role in down-regulating HIF-1α activity and can be a prospective anticancer drug.

Molecular dynamic simulations based discovery and development of thiazolidin-4-one derivatives as EGFR inhibitors targeting resistance in non-small cell lung cancer (NSCLC)

Targeting kinases with oncogenic driver mutations in malignancies with allosteric kinase inhibitors is a promising new treatment technique. EGFR inhibitors targeting the L858R/T790M/C797S mutation bearing thiazolidine-4-one scaffold were discovered, optimized, synthesized, and biologically evaluated. According to in silico and in vitro studies, compounds 6a and 6b resulted to be highly potent with IC50 values of 120 nM and 134 nM and good selectivity. Compound 6a displayed significant antioxidant activity, with a DPPH radical scavenging value of 92.15%. The potency of compounds was also compared with ADMET and molecular dynamics simulations study. A comparative simulation of model protein and protein-ligand complex in presence and absence of compound 6a has been carried out. Communicated by Ramaswamy H. Sarma

Tuning of silica nanoparticle-lysozyme protein complexes in the presence of the SDS surfactant.

The structures of the complexes of anionic silica nanoparticle (size ∼ 16 nm)-lysozyme (cationic) protein, tuned by the addition of the anionic surfactant sodium dodecyl sulfate (SDS), have been investigated by dynamic light scattering (DLS) and small-angle neutron scattering (SANS). The unique advantage of contrast variation SANS has been used to probe the role of individual components in binary and ternary systems. The cationic lysozyme protein (at pH ∼ 7) adsorbs on the anionic silica nanoparticles and forms mass fractal aggregates due to the strong attractive interaction, whereas similarly charged SDS does not interact physically with silica nanoparticles. The presence of SDS, however, remarkably affects the nanoparticle-protein interactions via binding with the oppositely charged segments of lysozyme. In general, the SDS-lysozyme complexes possess a variety of structures (e.g., insoluble complexes of Ly(DS)8, crystalline structure, or micelle-like structure) depending on the surfactant-to-protein molar ratio (S/P). In the ternary system (HS40-lysozyme-SDS), lysozyme preferentially binds with SDS, instead of directly to nanoparticles. At low S/Ps (0 ≤ S/P ≤ 10), the SDS concentration is not enough to fully neutralize the charge of lysozyme, leading to the formation of cationic SDS-lysozyme complex-mediated nanoparticle aggregation. The morphology of the nanoparticle-(lysozyme-SDS) complexes is also found to be mass fractal kind where the fractal dimension increases with increasing SDS concentration. At S/P > 10, there is sufficient SDS to fully neutralize the lysozyme in the absence of competing charges from the particle but it is at S/P = 50 before all lysozyme desorbs from the particle and binds completely to the overwhelming amount of SDS, creating an oppositely charged lysozyme-SDS complex, which is repelled from the particle.

DNA interaction studies of Cu(II), Co(II), and Ni(II) chelates derived from schiff base ligand

Chelates of the type M(L)2 {where, M ​= ​Co(II), Ni(II) and Cu(II), and L ​= ​3-{(E)-[(2-hydroxy-3-methoxyphenyl)methylidene]amino}pyridin-4(1H)-one)} were synthesized by using the Schiff base ligand in the stochiometric ratio 2:1 (L:M) and Schiff base ligand (L) was synthesized by simple condensation between 2-hydroxy-3-methoxybenzaldehyde with 3-aminopyridin-4-ol. The structure and formation of synthesized compounds were established by different analytical and spectroscopic methods like, elemental analysis, UV- spectroscopy, FT-IR, Proton and Carbon NMR, mass spectrometry and Powder XRD. Further, the synthesized chelates screened for the DNA binding studies of Calf Thymus (CT)-DNA by exploiting electronic absorption spectra, relative viscosity measurements and thermal denaturation methods. The proposed DNA binding mode supports the enhancement in the binding activity of the complexes in presence of newly synthesized ligand. The cleavage activities of the PUC-18 DNA in the presence and the absence of the complexes were recorded with the help of gel-electrophoresis. The cleavage experiment results reveals that all the synthesized chelates can cleave pUC-18 DNA effectively.

Effect of hydrophilic polymer on solubility and taste masking of linezolid in multi-component cyclodextrin inclusion complex: Physicochemical characterization and molecular docking

The current work deals with the effect of hydrophilic polymer in a multi-component β-cyclodextrin (βCD) inclusion complex for enhancement of solubility and taste masking ability of linezolid (LZ). The phase solubility studies indicated the formation of 1:1 M stoichiometric ratio of LZ to βCD in all complexes in presence or absence of hydrophilic polymer (HPMC e5LV). The high stability constant (Ks; 1089 M−1, 1393 M−1), complexation efficiency (CE; 3.347, 3.761) and more negativity of Gibbs free energy (ΔG; −238.69, −1019.61) of ternary complexes in presence of 2.5% w/v and 5% w/v of HPMCe5LV was compared with binary system (Ks, 1024 M−1: CE, 2.571: ΔG, −59.91), which resulted in the improved complexation stability and solubilizing efficiencies. Solid inclusion complexes of LZ-βCD were prepared in 1:0.3 M ratio by kneading, co-evaporation, physical mixing and microwave irradiation methods with or without addition of HPMC e5LV. The drug content, solubility, dissolution and taste masking of LZ in ternary complexes were significantly higher (p < 0.05) than the binary complexes. The lowest MDT value (0.34 ± 0.007), highest value of DE (30mts) (28.9 ± 0.05) and R (15mts) (70.33 ± 0.57) were observed in case of solid inclusion complexes prepared by microwave irradiation method. The negative binding affinity found in molecular docking indicated the high stability of the ternary complex. No interaction was found in LZ, βCD and HPMC e5LV when analyzed by FTIR study. XRD and DSC results revealed that more amorphization of LZ in presence of βCD and HPMC e5LV. It infers that the multi-component system by microwave irradiation method can be a promising approach for increasing solubility with better palatability.

The effects of Cu, Zn doped, and static electrical field on the interaction of mercaptopyridine drug with B12P12 nanocage: Insight from DFT, TD-DFT

In the current work, the interaction of 4-Mercaptopyridine drug (4-MCP) with the pristine, Cu, and Zn doped boron phosphide nanocage (B12P12) in the absence and presence of static electrical field (SEF) were investigated by density functional theory (DFT) and TD-DFT methods at the cam-B3LYP/Lanl2DZ level of theory by Gaussian 09 software. The calculated results demonstrated that the adsorption of the 4-MCP from the N site on the B site of nanocage in the 4-MCP&B12P12 complex was more desirable than 4-MCP&CuB11P12, and 4-MCP&ZnB11P12 complexes. In the presence of static electrical field (SEFz+0.02, SEFz+0.03, and SEFz+0.04 au), the adsorption energy of 4-MCP&B12P12 complex in all adsorption models increases from the original state. On the other hand, the gap energy of 4-MCP&B12P12, 4-MCP&CuB11P12, and 4-MCP&ZnB11P12 complexes in presence of the SEF field decreases significantly from the pure state, thereby the conductivity and reactivity of nanocage increase significantly from the pure state. This result demonstrates that in the presence of a SEF field, the sensitivity of B12P12 to detect 4-MCP in the system increases, and this method is suitable for making a sensitive sensor for 4-MCP.The RDG (reduced density gradient), NBO (natural bond orbital), and AIM (atom in molecule) results confirm that the bond nature between 4-MCP and B12P12 nanocage in all studied complexes is a partially covalent bond type. The results of this study suggest that the application of an external electric field is important in the targeted adsorption and transport of drugs, as well as in determining the location of drugs in the body and boosting the therapeutic effect of the drug.

Solvent induced distortion in a square planar copper(II) complex containing an azo-functionalized Schiff base: Synthesis, crystal structure, in-vitro fungicidal and anti-proliferative, and catecholase activity

This research work reports the synthesis, single crystal X-ray structure, catechol oxidation, fungicidal and antiproliferative activity of a newly synthesized copper(II) complex, [Cu(L)2]H2O . CH3OH (1) containing an azo-functionalized Schiff base, HL = 2-methoxy-6-((Z)-((4-((E)-phenyldiazenyl)phenyl)imino)methyl)phenol. The crystal structure analysis reveals that the Cu(II) centre exists in a highly distorted square planar geometry. The crystallize water and methanol form a strong intermolecular association through H-bonding. More importantly, the H atoms of the lattice water interact with the O atoms of ligand units leading to 5- and 6-membered cycles through the H-bonding network and distort the square planar geometry. The copper(II) complex has emerged as a bioinspired catalyst in the oxidative transformation of 3,5-di-tert-butylcatechol (DTBC) to o-benzoquinone in methanol with a high turnover number, 4.75 × 102 h–1. Electrochemical analysis of the copper(II) complex in presence of DTBC recommends the generation of catechol/o-benzosemiquinone redox couple in the course of oxidation. The EPR spectral analysis of 1 in presence of DTBC was found silent and suggested the antiferromagnetic interaction between copper centre and benzosemiquinone species. The copper(II) complex turns out to be a potential fungicidal agent against clinical candida albicans and scanning electron microscope studies confirm the destruction of the fungal cell membrane with the deposition of copper. The IC50 value of the copper complex was determined as 15 µg/mL which suggests the excellent antiproliferative potency of the synthetic compound against the breast cancer cell lines, MCF-7.

Dissociation of the DCF-Hb complex in presence of cationic micelles: A spectroscopic and computational approach

Diclofenac sodium (DCF) is a derivative of phenyl acetic acid and a model representative of the family of non-steroidal anti-inflammatory drugs (NSAIDs). It is extensively consumed for treating inflammation and degenerative disorders like rheumatoid arthritis. The micelles or aggregates of surfactants have ability to solubilize poorly soluble drugs thereby increasing bioavailability of the drugs. Thus, in the current study we have shown a systematic approach for the association of diclofenac with haemoglobin and deintercalation of DCF from hemoglobin (Hb) by hexadecyltrimethylammonium bromide (CTAB) micelles by using various spectroscopic techniques. The fluorescence and UV–visible spectral results revealed that DCF interacts with CTAB micelles and resides in its hydrophobic core. Thus, steady fluorescence and UV–visible measurements provides a strong sign for the relocation of DCF molecules from the hemoglobin interior to the micellar interface of CTAB above cmc. The CD results hinted that CTAB micelles do not disturb the structure of hemoglobin, which further supported that CTAB micelles can be applied as a reliable delivery vehicle for DCF. The present study may be significant for the discovery of improved micelle-based vehicles to the delivery of non-steroidal anti-inflammatory drugs in their targeted site.

A fluorescence turn-down-up detection of Cu2+ and pesticide quinalphos using carbon quantum dot integrated UiO-66-NH2

Synthesis of a fluorescent probe consisting of carbon quantum dot integrated metal–organic framework (OPCD@UiO-66-NH 2 ) via a facile one-pot route has been reported. Carbon dot derived from orthophenylenediamine (OPCD) with a PLQY (26%) has been deposited on UiO-type metal organic framework by introducing OPCD during the synthesis of MOF. The resulting fluorescent OPCD@UiO-66-NH 2 composite shows better fluorescence properties as well as photostability than pristine OPCD. The molecular interaction between UiO-66-NH 2 and Cu 2+ can be sensed by encapsulated OPCD. As a result the OPCD@UiO-66-NH 2 shows remarkable fluorescence quenching on addition of Cu 2+ . However, in presence of organophosphorus pesticide quinalphos, the fluorescence intensity (at λ 425 ) of CD@UIO-66-NH 2 is regained because of competitive binding of Cu 2+ with quinalphos and releasing OPCD@UIO-66-NH 2 to the medium. Thus a dual sensor for Cu 2+ and quinalphos can be established by measuring fluorescence intensity at λ 425 . The relative increase in fluorescence intensity for quinalphos (F/F 0 ) works linearly in the concentration range 0–16 μM and the limit of detection is found to be 0.3 nM. The specific and selective recognition of our probe towards organophosphorus pesticide quinalphos makes it suitable for real field applications. • A carbon dot integrated UiO fluorescence sensor has been designed for detection of quinalphos in aqueous medium. • The sensing mechanism is based on disruption of non-radiative CD@UiO-Cu 2+ complex in presence of quinalphos. • The limit of detection is 0.3 nM which is lowest among the published papers. • The sensors can be successfully used to detect quinalphos in real samples.

Time-dependent conformational analysis of ALK5-lumican complex in presence of graphene and graphene oxide employing molecular dynamics and MMPBSA calculation

Lumican, an extracellular matrix protein avails wound healing by binding to ALK5 membrane receptor (TGF-beta receptor I). Their interaction enables epithelialization and substantiates rejuvenation of injured tissue. To enrich permanence of ALK5-lumican interaction, we employed graphene and graphene oxide co-factors. Herein, this study explicates concomitancy of graphene and graphene oxide with ALK5-lumican. We performed an in silico approach involving molecular modelling, molecular docking, molecular dynamics for 200 ns, DSSP analysis and MMPBSA calculations. Results of molecular dynamics indicate cofactors influential in altering bioactive site of lumican than ALK5. Similarly, MMPBSA calculations unveiled binding energy of apoenzyme as −108.09 kcal/mol, holoenzyme (G) as −79.20 kcal/mol and holoenzyme (GO) as −114.33 kcal/mol. This concludes graphene oxide lucrative in enhancing binding energy of ALK5-lumican in holoenzyme (GO) via coil formation of Lum C13 domain. In contrast, graphene reduced binding energy of ALK5-lumican in holoenzyme (G) modifying Lum C13 into beta sheets. MMPBSA residual contribution analysis of Lum C13 residues revealed binding energy of −13.9 kcal/mol for apoenzyme, −6.8 kcal/mol for holoenzyme (G) and −19.5 kcal/mol for holoenzyme (GO). This supports coil formation propitious for better ALK5-Lum interaction. Highest SASA energy of −21.05 kcal/mol of holoenzyme (G) assures graphene reasonable for improved ALK5-lumican hydrophobicity. As per the motive of the study, graphene oxide enriches permanence of ALK5-lumican. This provides counsel for plausible exploitation of lumican and graphene oxide as targeted/nano drug delivery system to reinstate acute wounds, chronic wounds, corneal wounds, hypertrophic scars and keloids in near future. Communicated by Ramaswamy H. Sarma