Site Ligands Research Articles

Energetic metal-organic framework based on multinuclear clusters of Cu(II) and Fe(III) and its catalytic action on thermal decomposition of solid propellant components (RDX, HMX, CL-20 and AP)

Using nitrogen-rich tetrazole derivatives with multifunctional groups and ligand sites in metal–organic frameworks (MOFs) is a strategy to enhance their energy levels and broaden their applications. In the present study, a Cu(II) and Fe(III) heteronuclear {[CuFe3O(tza)6(H2O)3]·(NO3)2·OH}n (CuFe-MOF) based on the high-energy ligand tetrazole-1-acetic acid (Htza) was synthesized and its structures and properties were evaluated. The effects of CuFe-MOF as a catalyst on the thermal decomposition performance of the solid propellant components (RDX, HMX, CL-20 and AP) were investigated. The results demonstrated that the successfully prepared compound, an infinite 3D meshwork structure composed of [Fe3O(tza)6]+ and Cu2+, is in the ortho-hexagonal crystal system, P63/m space group. CuFe-MOF exhibited good thermal stability (Tdec = 238.9 °C) and insensitivity to impact (IS > 40 J) and friction (FS > 360 J). The addition of 5 % CuFe-MOF significantly reduces the decomposition peak temperature (1.9 °C, 5.8 °C, 5.7 °C and 71.4 °C) and apparent activation energy (38.5 kJ·mol−1, 38.3 kJ·mol−1, 63.9 kJ·mol−1, and 27.0 kJ·mol−1) of the RDX, HMX, CL-20, and AP compared to the raw materials while notably enhancing the heat release (509.8 J·g−1, 613.1 J·g−1, 578.4 J·g−1 and 584.3 J·g−1). Furthermore, good compatibility with RDX, HMX, CL-20, and AP was demonstrated using VST method. This research indicates the potential of {[CuFe3O(tza)6(H2O)3]·(NO3)2·OH}n as a promising alternative to the existing inert catalysts in propellants containing RDX, HMX, CL-20, and AP components, serving as an energetic combustion catalyst.

Economic optimization of antibody capture through Protein A affinity nanofiber chromatography

In this study we compare a nanofiber device and a resin column, both with the same Protein A ligand, for the capture of four different monoclonal antibodies and a trivalent crystallizable fragments (Fc) of antibody. We show that the dynamic binding capacity of the nanofiber device varies slightly with residence time, with the transfer kinetics slower for the IgG1, than for the IgG4 antibody. Surface plasmon resonance shows that the trivalent Fc binds to multiple Protein A ligand sites due to its three repeating Fc units, whereas multiple IgG antibodies bind to a single Protein A ligand. The nanofiber device gives comparable eluate purity to the resin column but at lower antibody concentrations due to its larger housing volume and lower binding capacity. It can be used for up to 200 cycles without performance loss and gives consistent eluate quality when scaled from 0.4 mL to 3.75 mL. We show that the use of a single nanofiber device to process one 2000 L clarified harvest through multiple cycles can reduce the Cost of Goods fivefold compared with a resin column. Costs are potentially lower for up to thirteen 2000 L harvests if device reuse can be validated. Nanofiber devices are thus an attractive option for manufacture of pre-clinical or clinical trial material where the number of batches is limited.

Biophysical Mechanism of Allosteric Regulation of Actin Capping Protein

Actin capping protein (CP) can be regulated by steric and allosteric mechanisms. The molecular mechanism of the allosteric regulation at a biophysical level includes linkage between the binding sites for three ligands: F-actin, Capping-Protein-Interacting (CPI) motifs, and V-1/myotrophin, based on biochemical functional studies and solvent accessibility experiments. Here, we investigated the mechanism of allosteric regulation at the atomic level using single-molecule Förster resonance energy transfer (FRET) and molecular dynamics (MD) to assess the conformational and structural dynamics of CP in response to linked-binding site ligands. In the absence of ligand, both single-molecule FRET and MD revealed two distinct conformations of CP in solution; previous crystallographic studies revealed only one. Interaction with CPI-motif peptides induced conformations within CP that bring the cap and stalk closer, while interaction with V-1 moves them away from one another. Comparing CPI-motif peptides from different proteins, we identified variations in CP conformations and dynamics that are specific to each CPI motif. MD simulations for CP alone and in complex with a CPI motif and V-1 reveal atomistic details of the conformational changes. Analysis of the interaction of CP with wild-type (wt) and chimeric CPI-motif peptides using single-molecule FRET, isothermal calorimetry (ITC) and MD simulation indicated that conformational and affinity differences are intrinsic to the C-terminal portion of the CPI motif. We conclude that allosteric regulation of CP involves changes in conformation that disseminate across the protein to link distinct binding-site functions. Our results provide novel insights into the biophysical mechanism of the allosteric regulation of CP.

Experimental and theoretical studies on structural aspects of transition metal complexes of isonicotinoyl N‐oxide hydrazone: Their DNA‐binding interaction and cytotoxicity

Equilibrium studies of isonicotinoyl N‐oxide hydrazone [4‐(2‐(4‐(diethylamino)‐2‐hydroxybenzylidene) hydrazine carbonyl) pyridine1‐oxide] were carried out by employing pH‐metric titrations in 40% DMF‐H2O medium at 303 K and 0.1 M ionic strength, to investigate its ligation properties. Quantitative structure activity relationship (QSAR) and molecular orbital properties were evaluated by applying HyperChem 7.5 tools. The title compound and its Cu (II), Ni (II), and Zn (II) complexes were characterized by various spectro analytical tools, namely, Fourier‐transform infrared spectroscopy, 1H‐nuclear magnetic resonance, liquid chromatography‐mass spectrometry, UV‐Vis, thermogravimetric analysis–differential thermal analysis, scanning electron microscope (SEM)–energy‐dispersive X‐ray, electron spin resonance, and X‐ray diffraction (XRD) studies. Infrared data provided information about the chelating properties of ligand and coordination sites in metal complexes. The electronic spectral studies of complexes inferred the symmetry‐based spin allowed electronic transitions and charge transfer (CT) transitions. Mass spectral studies, elemental analysis, and thermal studies of complexes confirmed the composition of the metal complexes. The surface texture and nanocrystalline nature of solid compounds were studied by SEM and XRD methods. The antioxidant activities of all the compounds were determined by DPPH radical scavenging method. DNA‐binding interactions of the synthesized compounds with calf thymus (CT)‐DNA were studied by absorption and fluorescence methods. Antioxidant and antimicrobial studies indicated their potentiality as active agents. Cytotoxicity measurements of title compounds for IC50 values on MCF‐7 cell line, and docking scores of these compounds with chosen target, computed by employing AutoDock software indicated their potential for anticancer properties.

Identifiability of equilibrium constants for receptors with two to five binding sites.

Ligand-gated ion channels (LGICs) are regularly oligomers containing between two and five binding sites for ligands. Neither in homomeric nor heteromeric LGICs the activation process evoked by the ligand binding is fully understood. Here, we show on theoretical grounds that for LGICs with two to five binding sites, the cooperativity upon channel activation can be determined in considerable detail. The main requirements for our strategy are a defined number of binding sites in a channel, which can be achieved by concatenation, a systematic mutation of all binding sites and a global fit of all concentration-activation relationships (CARs) with corresponding intimately coupled Markovian state models. We take advantage of translating these state models to cubes with dimensions 2, 3, 4, and 5. We show that the maximum possible number of CARs for these LGICs specify all 7, 13, 23, and 41 independent model parameters, respectively, which directly provide all equilibrium constants within the respective schemes. Moreover, a fit that uses stochastically varied scaled unitary start vectors enables the determination of all parameters, without any bias imposed by specific start vectors. A comparison of the outcome of the analyses for the models with 2 to 5 binding sites showed that the identifiability of the parameters is best for a case with 5 binding sites and 41 parameters. Our strategy can be used to analyze experimental data of other LGICs and may be applicable to voltage-gated ion channels and metabotropic receptors.

Selective Radical Transfer in a Series of Nonheme Iron(III) Complexes.

A series of nonheme iron complexes, FeIII(BNPAPh2O)(Lax)(Leq) (Lax/eq = N3-, NCS-, NCO-, and Cl-) have been synthesized using the previously reported BNPAPh2O- ligand. The ferrous analogs FeII(BNPAPh2O)(Lax) (Lax = N3-, NCS-, and NCO-) were also prepared. The complexes were structurally characterized using single crystal X-ray diffraction, which shows that all the FeIII complexes are six-coordinate, with one anionic ligand (Lax) in the H-bonding axial site and the other anionic ligand (Leq) in the equatorial plane, cis to the Lax ligand. The reaction of FeIII(BNPAPh2O-)(Lax)(Leq) with Ph3C• shows that one ligand is selectively transferred in each case. A selectivity trend emerges that shows •N3 is the most favored for transfer in each case to the carbon radical, whereas Cl• is the least favored. The NCO and NCS ligands showed an intermediate propensity for radical transfer, with NCS > NCO. The overall order of selectivity is N3 > NCS > NCO > Cl. In addition, we also demonstrated that H-bonding has a small effect on governing product selectivity by using a non-H-bonded ligand (DPAPh2O-). This study demonstrates the inherent radical transfer selectivity of nonhydroxo-ligated nonheme iron(III) complexes, which could be useful for efforts in synthetic and (bio)catalytic C-H functionalization.

Structural determinations of homo and heterodi- or tetra-nuclear lanthanide complexes and their characterization by μ-Squid experiments

Two families of homo- and heterodinuclear complexes are prepared and structurally characterized, thus demonstrating that genuine complexes involving two lanthanide ions closely located in the lanthanide series can be obtained, taking into account a simple rule that necessitates introduction of the better Lewis acid Ln ion (the smallest Ln ion) into the inner coordination site of the main ligand used in this synthesis. In the first family, the presence of a deprotonated orthovanillin ligand (ovan) around the Ln ion positioned in the outer coordination site of the main ligand allows a good isolation of the dinuclear complexes. These complexes behave as SMSs when a Dy ion is coordinated in the outer site but a weak magnetic magnetic Ln-Dy interaction is needed to create a weak magnetic field able to suppress collapsing of the hysteresis loops in zero external applied field at very low temperature. In the second family, the ovan ligand is replaced by a chloride ligand, so that two dinuclear units are linked together by two Cl…HOMe hydrogen bonds to yield tetranuclear complexes that are not SMMs. Eventually these two preparation pathways are expected to give novel and genuine examples of homo or hetero-dinuclear and tetranuclear lanthanide complexes likely to furnish in future coordination complexes useful in quantum computing.

Targeting of HPV E6 at the binding sites to the host-cell E6AP, p53, and the endoplasmic reticulum-resident chaperone, GRP78

Background: Human papillomavirus (HPV) represents an etiological factor for many cancer types, especially cervical cancer. Its oncoprotein E6 sheds drug designers who aim to stop its cellular protein associations, such as p53 and E6AP. Recently, it was discovered that the host-cell chaperone glucose-regulated protein 78 (GRP78) plays a crucial function in HPV infectivity by association with the viral E6 and E7 proteins. Therefore, we aimed to test small molecules inhibitor that could contradict the association between E6 and cellular factors E6AP, GRP78, and p53. Methods: In this study, molecular docking protocol was elaborated to test 115 small molecule compounds against the three binding sites of HPV E6 to the host-cell proteins; E6AP, p53, and GRP78. After that, molecular dynamics simulation and free energy calculations were performed on the best three complexes. Results: The results reveal the potency of 18 compounds against the HPV E6 at different binding sites, which give lower free energies than paclitaxel (positive control). The best two compounds, hypericin, and anabsinthin, could bind effectively and stably during the 100 ns MD simulation period to HPV E6. The calculated average free energies for hypericin and anabsinthin are −18.76 and −14.40 kcal/mol, respectively. They formed stable complexes with the three binding sites by forming hydrophobic contacts. The key residues that stabilize the two ligands in HPV E6 binding sites are V31, Y32, V62, and Y70 (E6AP), P13, C16, T22, I23 and A46 (p53), and M1, V31, L50, L67, and Q107 (GRP78). Conclusions: The best two compounds, hypericin, and anabsinthin, are potential candidates against HPV E6 at the host-cell factors binding sites, hence could block the oncoprotein activity of E6 in infected cells. Further experimental validation is yet to be performed and suggested as future work. Communicated by Ramaswamy H. Sarma

In silico Exploration on The Potency of Basil (Ocimum basilicum) as an Anti-Aging Skin Agent

New and improved skin care products and procedures have been established by technological advances and scientific investigation. By increasing the skin's moisture, firmness, and elasticity, anti-aging skin care can enhance the skin's overall condition. The objective of this study was to examine the potential of basil's chemical compounds as an in silicoanti-aging agent. Exploration of online databases, scholarly articles from national and international journals, and analysis using docking software are selected as examples of data collection methods. Matrix metalloproteinase 1 (MMP1), with PDB code 966C, is one of the targeted proteins related to skin anti-aging. Ladanein, acacetin, luteolin, 5-hydroxy-7,4'-dimethoxyflavone and genkwanin are five basil compounds that are predicted to exhibit anti-aging agents based on the presence of the binding affinity score indicator and the similarity of the appropriate attachment sites compared to the native ligand used. The scores for the binding affinity of luteolin, ladanein, acacetin, 5-hydroxy-7,4'-dimethoxyflavone, and genkwanin are -10, -9.9, -9.9, -9.8, and -9.6 kcal/mol, respectively. At the attachment positions of five basil compounds, the interactions with ASN 180, LEU 181 and ALA 182 key amino acids, which are the attachment sites for the native ligands, were also formed.

THU578 Concept: Role Of Spiral Steroids (SS) During Pregnancy

Abstract Disclosure: F.I. Chasalow: None. Background: Earlier, my laboratory reported 3 novel endogenous steroids (SS) that cross react with digoxin-specific antibodies (DLM). The SS are readily distinguished from all other steroids by 3 characteristics: [1] each is a phosphocholine diester, [2] each has more than 21 carbon atoms in the steroid fragment and [3] the extra carbons form an E-ring with a cyclic lactone. The discovery included a biosynthetic scheme with known enzymes and no need for a ‘magic’ step. Function: NaK-ATPase has 3 subunits, designated FXYD, α, and β. Affinity for Na+ and K+ ions is regulated by FXYD proteins. Each SS matches a tissue-specific α-subunit. Each α-subunit has 2 different binding sites for steroids. One site binds a SS; the ligand of the other site is unknown. For example, Ionotropin is specific for the α subunit present in cardiac and renal tissue. Kaleotropin is isolated from gonads, but the α subunit which matches each specific ovarian cell type is unknown. Galotropin (G-trop): One of the SS, G-trop, was detected as a DLM in human breast cyst fluids, specifically cysts with high K+ ion levels. Solubility properties distinguished it from previously known cardiac glycosides and, like other DLM, it inhibited NaK-ATPase. G-trop was also detected in milk from cows, sheep and goats. Ions derived from Ionotropin (m/z=341 Da) or Kaleotropin (m/z=369 Da) were not present in milk extracts. On LC-MS, G-trop fragmented to an ion at m/z= 381 Da. Trial and error analysis suggests C25O4H34. No other formula is consistent with m/z=381 Da. G-trop: G-trop wasn’t present in serum from children. At 22-26 weeks of gestation, whether or not a pregnant woman had pre-eclampsia, serum had low levels of G-trop. Maternal G-trop increases during the 3rd trimester, coincidentally with initiation of milk production; simultaneously, K+ ion levels in milk increased. Pre-eclampsia. In a pilot study, 65% of patients (n=20) with pre-eclampsia had elevated levels of Ionotropin precursor and 30% had elevated levels of Kaleotropin precursor. 25% of patients with pre-eclampsia develop life-threatening hypertension or seizures, typical of the expected response to elevated Ionotropin levels. Therapy includes immediate delivery of the infant at 30-36 weeks of gestation. Maternal G-trop synthesis has not yet begun and mother’s milk has low K+ ion levels. Elevated maternal Kaleotropin is not the cause of maternal hypertension, suggesting a specific gestational maternal α-subunit is its target. Kaleotropin from placenta may be the signal to respond to maternal hypokalemia. Necrotizing enterocolitis (NEC):In utero the fetus does not absorb K+ from the GI tract because fetal need for K+ ion is provided via the placenta. Concept: After premature delivery, without G-trop in milk, the infant can’t absorb K+ from the GI tract; the GI tract fails to grow and tight junctions do not form. As a result, infants are at high risk for developing NEC. Presentation Date: Thursday, June 15, 2023

Inhibitions of monoamine oxidases by ferulic acid hydrazide derivatives: synthesis, biochemistry, and computational evaluation

Monoamine oxidases (MAOs) regulate neurotransmitters, and changes in their regulation lead to neurogenerative diseases (NDs). Therefore, MAO inhibitors are used to treat NDs. Ferulic acid, a phenolic compound found in various plant species, has been demonstrated to have a variety of biological functions, including anti-inflammatory, anticancer, and neuroprotective effects. In this study, ten ferulic acid hydrazide derivatives (FA1–FA10) were synthesized, and their ability to inhibit monoamine oxidase (MAO) enzymes was tested. Six candidates demonstrated a more pronounced pattern of inhibitory action against MAO-B than against MAO-A. FA3 had the highest inhibitory efficacy in MAO-B inhibition (IC50 value of 1.88 μM), followed by FA9 (2.08 μM). FA3 has a Ki of 1.92 ± 0.73 μM. A reversibility experiment of MAO-B inhibition by FA3 was conducted using dialysis, and the recovery pattern showed FA3 was a reversible MAO-B inhibitor with a similar recovery to safinamide, a reversible reference inhibitor. These results indicate that FA3 is an effective reversible MAO-B inhibitor. In molecular dynamics and docking, FA3 paired with pi-pi stacking helped stabilize the protein ligand in the active site of MAO-B. According to this study, lead compounds can be used as therapeutic agents to treat neurological conditions, such as Parkinson's disease (PD).

Interaction of Synthetic Cannabinoid Receptor Agonists with Cannabinoid Receptor I: Insights into Activation Molecular Mechanism.

Synthetic cannabinoid receptor agonists (SCRAs) have become a wide group of new psychoactive substances since the 2010s. For the last few years, the X-ray structures of the complexes of cannabinoid receptor I (CB1) with SCRAs as well as the complexes of CB1 with its antagonist have been published. Based on those data, SCRA-CB1 interactions are analyzed in detail, using molecular modeling and molecular dynamics simulations. The molecular mechanism of the conformational transformation of the transmembrane domain of CB1 caused by its interaction with SCRA is studied. These conformational changes allosterically modulate the CB1-Gi complex, providing activation of the Gi protein. Based on the X-ray-determined structures of the CB1-ligand complexes, a stable apo conformation of inactive CB1 with a relatively low potential barrier of receptor activation was modeled. For that model, molecular dynamic simulations of SCRA binding to CB1 led to the active state of CB1, which allowed us to explore the key features of this activation and the molecular mechanism of the receptor's structural transformation. The simulated CB1 activation is in accordance with the previously published experimental data for the activation at protein mutations or structural changes of ligands. The key feature of the suggested activation mechanism is the determination of the stiff core of the CB1 transmembrane domain and the statement that the entire conformational transformation of the receptor to the active state is caused by a shift of alpha helix TM7 relative to this core. The shift itself is caused by protein-ligand interactions. It was verified via steered molecular dynamics simulations of the X-ray-determined structures of the inactive receptor, which resulted in the active conformation of CB1 irrespective of the placement of agonist ligand in the receptor's active site.

Sustainable antimony management via porphyrin ligand-based MOFs: From enrichment of antimony from water to the utilization in SbO2– based aqueous batteries

Antimony-based materials are rapidly developing towards industrialization, making it crucial to control potential toxicity and address sustainable antimony management. A strategy has been proposed to remove antimony from wastewater and sustainably convert the resulting antimony-enriched waste adsorbent into electrode materials. Herein, the porphyrin ligand-based zirconium metal-organic framework (PCN-222) was constructed for antimony adsorption. The antimony is initially adsorbed onto the Zr cluster nodes, spreads along the skeleton through hydrogen bonds, and finally terminates at the N-coordination fixed sites in the porphyrin ligand. Afterwards adsorption, the antimony-enriched waste adsorbent is converted to Sb nanoparticles embedded in N-doped porous carbon composite by one-step carbothermal reduction. The composite is applied into SbO2--based aqueous alkaline battery, which displays a high specific capacity with 122.5 mAh/g at 1 A/g and good cycling stability. The work provides valuable insights into the treatment of contaminated water and the management of antimony resources.

Synthesis and crystal structure of bis-(tert-butyl isocyanide-κC)[5,10,15,20-tetra-kis-(4-chloro-phen-yl)porphyrinato-κ4N]iron(II).

In the title compound, [FeII(C44H24Cl4N4)(C5H9N)2] or [FeII(TClPP)(t-BuNC)2] [where TClPP and t-BuNC are 5,10,15,20-tetra-kis-(4-chloro-phen-yl)porphyrinate and tert-butyl isocyanide ligands, respectively], the metal ion lies on an inversion center and is octa-hedrally coordinated by the N atoms of the porphyrin ring in the equatorial plane and by carbon atoms of the trans t-BuNC ligands in the axial sites. The Fe-N bond length of 2.0074 (14) Å suggests a low-spin complex (S = 0). The crystal packing of the title compound is sustained by C-H⋯Cl, C-H⋯N and C__H⋯Cg (Cg = the centroid of a pyrrole ring of the TClPP porphyrinate) inter-actions, leading to a three-dimensional network. The Hirshfeld surface (HS) analysis indicates that 61.4% of the inter-molecular inter-actions are from H⋯H contacts while other contributions are from C⋯H/H⋯C, O⋯H/H⋯O and N⋯H/H⋯N inter-actions, which comprise 21.3%, 13.3% and 3.6% of the HS, respectively.

Study of G protein coupling receptors

G-protein coupled receptor is a type of cell membrane receptor that plays a crucial role in cellular signaling and is involved in various physiological processes in the human body. They are involved in transmitting signals from the extracellular environment to the inside of the cell, which ultimately leads to various cellular responses. The basic structure of a GPCR consists of a single polypeptide chain that crosses the cell membrane seven times, forming seven transmembrane helices. These helices create a pocket or cleft on the cell surface that acts as the binding site for specific ligands, such as hormones, neurotransmitters, or other signaling molecules. Overall, GPCRs are essential components of cellular communication and play vital roles in maintaining homeostasis and regulating various physiological functions in the human body. This review presents a comprehensive analysis of GPCR structure, mechanism, and physiological relevance, offering a novel framework for comprehending GPCR biology.

Theoretical investigations into the Spectrophotometrically Analyzed Niobium (V)-6-Chloro-3-hydroxy-7-methyl-2-(2’-thienyl)-4H-chromen-4-one Complex

Abstract Pentavalent niobium cation forms a stable yellow-colored binary complex with 6-chloro-3-hydroxy-7-methyl-2-(2’-thienyl)-4H-chromen-4-one (CHMTC) in the ratio of 1:2. The complex is quantitatively extractable into carbon tetrachloride from HClO4 solution maintained at pH 1.26–1.75 and strictly adheres to Beer’s law as verified by the Ringbom plot with an optimized range of determination as 0.385–1.211 ppm of Nb(V). The ligand-metal complex system shows good precision, accuracy, sensitivity, and selectivity and handles satisfactorily the analysis of several samples of varying complexity. The results are highly reproducible as confirmed by statistical data. The stability of the complex is theoretically confirmed with the help of HOMO-LUMO values and the energy gap [for CHMTC, ΔE gap = 3.62 V and for Nb(V)-CHMTC Complex, ΔE gap = 2.97 eV]. The reactivity descriptors were calculated for detailed computational study to probe into the chemical behavior of the studied ligand and its complex. Further, mapped electrostatic potential diagrams help in justifying the donor sites of CHMTC ligand which is in accordance with the analytical findings.

Development of molecular cluster models to probe pyrite surface reactivity.

The recent discovery that anaerobic methanogens can reductively dissolve pyrite and utilize dissolution products as a source of iron and sulfur to meet their biosynthetic demands for these elements prompted the development of atomic-scale nanoparticle models, as maquettes of reactive surface sites, for describing the fundamental redox steps that take place at the mineral surface during reduction. The given report describes our computational approach for modeling n(FeS2 ) nanoparticles originated from mineral bulk structure. These maquettes contain a comprehensive set of coordinatively unsaturated Fe(II) sites that are connected via a range of persulfide (S2 2- ) ligation. In addition to the specific maquettes with n = 8, 18, and 32 FeS2 units, we established guidelines for obtaining low-energy structures by considering the pattern of ionic, covalent, and magnetic interactions among the metal and ligand sites. The developed models serve as computational nano-reactors that can be used to describe the reductive dissolution mechanism of pyrite to better understand the reactive sites on the mineral, where microbial extracellular electron-transfer reactions can occur.

Structure-odor relationship in pyrazines and derivatives: A physicochemical study using 3D-QSPR, HQSPR, Monte Carlo, molecular docking, ADME-Tox and molecular dynamics

In this study, using both 2D-QSPR and 3D-QSPR approaches, to understand the structure-odor relationship of 78 1–4-pyrazine odorant molecules and to use this knowledge for the design of new food and flavor products. According to our results, the developed models have good predictability such as the HQSPR/BC model with QLOO2=0.832, R2 = 0.916, CoMSIA/SEH model with Q2 = 0.624, Rcv2 = 0.590, Rncv2 = 0.932, Rbs2 = 0.963, and Topomer CoMFA model withRtraining2 = 0.899, Rtest2 = 0.916. The Monte Carlo method was used in the creation of a Quantitative Structure-Property Relationship (QSPR) model. The molecular structure is represented using optimized Simplified Molecular Input Line Entry System (SMILES) and molecular descriptors. The performance of the model is evaluated using the Correlation Ideality Index (IIC) and the Correlation Contradiction Index (CCI). The best model, designated as TF2, boasts excellent statistical properties with a training R-squared value of 0.957 and a test R-squared value of 0.834. The model was then used to determine promoter activity levels, which formed the basis for the design of 36 new odorant molecules. Molecular docking and pharmacokinetic properties were used to explain the mode of binding between the proposed compounds and the active site of the Porcine Odorant Binding Protein complexed with pyrazine (2-isobutyl-3-methoxypyrazine). Molecular dynamic simulation was used to assess and justify the stability of the ligand in the active site of the receptor. The results of this study provide a basis for the discovery of new compounds with lower olfactory thresholds and diverse pharmacological properties.

Electrocatalytic and Spectroscopic Studies on Cytochrome Bd Oxidase, a Highly Diverse Bacterial Defense Factor

The selective reduction of oxygen to water is crucial to life and a central process in aerobic organisms. It is catalyzed by several different enzymes, including cytochrome bd oxidases that are solely present in prokaryotes, including several pathogens. In addition, these enzymes play a crucial role in protection against oxidative stress, in virulence, adaptability and antibiotics resistance. The reduction of O2 occurs at the high spin D-type heme in all cytochrome bd oxidases, that is also the binding site for several ligands from signaling processes, including NO, H2S and CO.Here we present the electrocatalytic study of the cytochrome bd I and bd II oxidases from Escherichia coli (1,2) as well on other related bd oxidases. Structural parameters that are crucial for the reactivity towards oxygen are analyzed. The pH dependency of the binding and release of NO, an important signaling factor is presented. The influence of mutants in the proton channel on the NO release is discussed.(1) Grauel, A. Kägi, J. Rasmussen, T. Makarchuk, I. Oppermann, S. Moumbock, A., Wohlwend, D., Müller, R., Melin, F., Günther, S., Hellwig, P., Böttcher, B., and Friedrich, T., ‘Structure of Escherichia coli cytochrome bd-II type oxidase with bound aurachin D’ (2021) Nat. Commun., 12:6498.(2) Nikolaev, A., Safarian, S., Thesseling, A., Wohlwend, D., Friedrich, T., Michel, H., Kusumoto, T., Sakamoto, J., Melin, F., Hellwig P. ‘Electrocatalytic evidence of the diversity of the oxygen reaction in the bacterial bd oxidase from different organisms’ (2021) Biochim. Biophys. Acta 1862, 148436.

Synthesis, Identification and Spectral Studies of Some New Schiff base ligand Complexes Contained 3,4-Diaminobenzophenone and pyridoxal hydrochloride Compounds

Anew Schiff base ligand. (HMPHM) 3-((4-chlorobenzylidene)amino)-4-((€-(3-hydroxy-5-(hydroxyl methyl)-2-Methyl)puridin-4-yl)methylene)amino)phenyl)(phenyl)methanon has been Prepared from reacting(3-amino-4-(((3-hydroxy-5-(hydroxylmethyl)-2-methylpyridin-4-yl)methylene)amino)phenyl)(phenyl)methanone with P-Chloro benzaldehyde Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Au(III) ions were used to create a new series of chelate complexes. The structures of the new Schiff base ligand and their transition metal complexes were characterized by using Fourier-transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H-NMR) technique, ultraviolet visible spectroscopy (UV-Vis), mass analysis, molar conductance, and magnetic susceptibility. [(M)(L)2] where M = Co(II), Ni(II), Cu(II), Zn(II), and Cd(II), and [(M)(L)Cl]Cl where M = Au (III). The coordination sites of the Schiff base ligand were revealed by FTIR to be through oxygen of the hydroxyl group, and the nitrogen of azomethine groups. Based on data obtained, the octahedral geometry was suggested for all ligand complexes exception of the Au(III) complex, which had a square planar geometry.