Structural Moieties Research Articles

SPECTROPHOTOMETRIC FINGERPRINTING AND CHEMICAL DETERMINATION OF STREPTOMYCIN, AMIKACIN, NEOMYCIN, AND GENTAMYCIN SULPHATE BY CONDENSING WITH NINHYDRIN REAGENT

Objective: The study aimed to develop a simple, efficient, inexpensive, rapid, and reproducible spectrophotometric analytical technique for aminoglycosides analysis by condensing with ninhydrin reagent. Methods: At a pH of 8.0, different aminoglycosides, including amikacin, gentamycin, neomycin, and streptomycin, were deaminated by the ninhydrin reagent. The working standard solution for each component was accurately placed into a series of 10 ml calibrated volumetric flasks, then 1 ml of the ninhydrin reagent was added and heated in a water bath for 15 min. The wavelength(s) of maximum absorption(s) was recorded after scanning the resultant purple complex from 350 nm to 930 nm. The final working concentrations ranged between 1600 and 2000 ug/ml. Results: The average weight of a neomycin sulphate tablet was 0.747g, with a standard deviation of 0.667%. After complexing with ninhydrin reagent at pH 6.0 for 10 to 15 min, all aminoglycosides developed purple coloration that lasted beyond 24 h, compared to the initial white, pale yellow, and colorless appearance of streptomycin, amikacin, neomycin, and gentamycin, respectively. The scanned spectra of the purple complex of ninhydrin formed after reaction with aminoglycosides in the visible region (350-900 nm) were similar, indicating the presence of a common parent structural moiety. At 550 nm, 650 nm, 750 nm, and 850 nm, distinct absorptions were observed. Amikacin, Streptomycin, and Gentamicin had the highest absorbance between 800 and 900 nm. After the reaction with ninhydrin, three distinct absorbances were observed in the Neomycin spectrum: between 380 and 400 nm, 580 and 600 nm, and around 800 nm. The comparative spectra for the four aminoglycosides and ninhydrin reagent with blank show a unique feature for the compounds. The coefficients of regression were 0.996 and 0.995, respectively. Conclusion: The proposed methods for analyzing streptomycin in streptomycin injections were successful. The percentage purity ranged from 017–110 % at 650 and 850 nm, which corresponds to the British Pharmacopoeia (BP) limit that streptomycin sulphate tablets should be between 97.00 and 110%.

Carbon dot complimentary green corrosion inhibitor for crystallographically textured Beta C titanium alloy for marine application: A state of art

The corrosion properties of Beta C titanium alloy were shown to differ remarkably, by more than one order of magnitude, with the crystallographic texture. More specifically, the maximum volume fraction of γ-fiber (ND//< 111 >) and large-sized grains were preferentially engineered by heat treatment to provide a corrosion-resistant surface. It was proposed that the ND//< 111 > grains, with lower dislocation content, are key in preferentially limiting corrosion. For 90% rolled plus annealed beta titanium alloy, the lowest corrosion current density, and maximum impedance were attained in nitrogen-based carbon dots containing NaCl electrolyte. Analysis using ultraviolet spectroscopy, and X-ray diffraction showed that the heteroatoms in the structural moiety of the carbon dots effectively bond to the titanium surface by physiochemical interaction.

QSAR Study on the Antitumor Activity of Novel 1,2, 3-Triazole Compounds based on Topomer Comfa Method

Background: The high mortality rate of cancer is endangering human health, and the research and development of new anticancer drugs have the attention of scientists worldwide. Sulfonamides have become the focus of anticancer drug research. 1,2,3-triazole compounds can inhibit the formation of a variety of tumor cells. Based on the excellent antitumor activity exhibited by the 1,2,3-triazole compound skeleton, the sulfonamide moiety in the sulfonamide structure can be introduced into the triazole compound skeleton to obtain highly active anticancer drugs. Methods: The Topomer CoMFA method was used to study the three-dimensional quantitative structureactivity relationship of 58 new 1,2,3-triazole compounds with sulfa groups, and a 3D-QSAR model was obtained. Results: The cross-validation coefficient q2 is 0.545, the non-cross-correlation coefficient r2 is 0. 754, r_pred2 is 0.930, the optimal number of principal components N is 4, and the standard estimation error SEE is 0.319. These results show that the model has good internal and external forecasting capabilities. By searching for the R group in the Topomer search module and combining with the more active groups in the existing molecules, 6 new compounds with theoretically higher anti-HL-60 (leukemia cell line) activity are obtained. Conclusion: The prediction result of the Topomer CoMFA model is good, and the statistical verification is effective. The prediction results of ADMET show that the 6 new compounds meet the drug requirements and are expected to become potential anti-HL-60 inhibitors, providing guidance for the synthesis of anti-tumor drugs.

Mono- and binuclear complexes of copper(II) with dimethylaminomethyl derivatives of 2-naphthol and 6-quinolinol: synthesis and in vitro study of antitumor properties.

1-(Dimethylamino)methyl-6-quinolinol scaffold, a structural moiety of the molecule of anticancer drug topotecan, was modified into copper-containing products to study cytotoxic properties. New mononuclear and binuclear Cu(II) complexes with 1-(N, N-dimethylamino)methyl-6-quinolinol were synthesized for the first time. The same way Cu(II) complexes with 1-(dimethylamino)methyl-2-naphtol ligand were synthesized. The structures of mono- and binuclear Cu(II) complexes with 1-aminomethyl-2-naphtol were confirmed by X-ray diffraction. The obtained compounds were examined for in vitro cytotoxic activity against Jurkat, K562, U937, MDA-MB-231, MCF7, T47D, and HEK293 cells. The induction of apoptosis and the effect of novel Cu complexes on the cell cycle were investigated. The cells showed a higher sensitivity to mononuclear Cu(II) complex with 1-(N, N-dimethylamino)methyl-6-quinolinolligand. All synthesized Cu(II) complexes had higher antitumor activity than the drugs topotecan, camptothecin, and platinum containing cisplatin.

Synthesis and Evaluation of Diguanosine Cap Analogs Modified at the C8-Position by Suzuki-Miyaura Cross-Coupling: Discovery of 7-Methylguanosine-Based Molecular Rotors.

Chemical modifications of the mRNA cap structure can enhance the stability, translational properties, and half-life of mRNAs, thereby altering the therapeutic properties of synthetic mRNA. However, cap structure modification is challenging because of the instability of the 5'-5'-triphosphate bridge and N7-methylguanosine. The Suzuki-Miyaura cross-coupling reaction between boronic acid and halogen compound is a mild, convenient, and potentially applicable approach for modifying biomolecules. Herein, we describe two methods to synthesize C8-modified cap structures using the Suzuki-Miyaura cross-coupling reaction. Both methods employed phosphorimidazolide chemistry to form the 5',5'-triphosphate bridge. However, in the first method, the introduction of the modification via the Suzuki-Miyaura cross-coupling reaction at the C8 position occurs postsynthetically, at the dinucleotide level, whereas in the second method, the modification was introduced at the level of the nucleoside 5'-monophosphate, and later, the triphosphate bridge was formed. Both methods were successfully applied to incorporate six different groups (methyl, cyclopropyl, phenyl, 4-dimethylaminophenyl, 4-cyanophenyl, and 1-pyrene) into either the m7G or G moieties of the cap structure. Aromatic substituents at the C8-position of guanosine form a push-pull system that exhibits environment-sensitive fluorescence. We demonstrated that this phenomenon can be harnessed to study the interaction with cap-binding proteins, e.g., eIF4E, DcpS, Nudt16, and snurportin.

Structure-guided Mutagenesis Reveals the Catalytic Residue that Controls the Regiospecificity of C6-Indole Prenyltransferases.

Indole is a significant structural moiety and functionalization of the C-H bond in indole-containing molecules expands their chemical space, and modifies their properties and/or activities. Indole prenyltransferases (IPTs) catalyze the direct regiospecific installation of prenyl, C5 carbon units, on indole-derived compounds. IPTs have shown relaxed substrate flexibility enabling them to be used as tools for indole functionalization. However, the mechanism by which certain IPTs target a specific carbon position is not fully understood. Herein, we use structure-guided site-directed mutagenesis, in vitro enzymatic reactions, kinetics and structural-elucidation of analogs to verify the key catalytic residues that control the regiospecificity of all characterized regiospecific C6 IPTs. Our results also demonstrate that substitution of PriB_His312 to Tyr leads to the synthesis of analogs prenylated at different positions than C6. This work contributes to understanding of how certain IPTs can access a challenging position in indole-derived compounds.

Exploring the stabilizing effect on the i-motif of neighboring structural motifs and drugs

Cytosine-rich DNA sequences may fold into a structure known as i-motif, with potential in vivo modulation of gene expression. The stability of the i-motif is residual at neutral pH values. To increase it, the addition of neighboring moieties, such as Watson-Crick stabilized loops, tetrads, or non-canonical base pairs have been proposed.Taking a recently described i-motif structure as a model, the relative effect of these structural moieties, as well as several DNA ligands, on the stabilization of the i-motif has been studied. To this end, not only the original sequence but different mutants were considered. Spectroscopic techniques, PAGE, and multivariate data analysis methods have been used to model the folding/unfolding equilibria induced by changes of pH, temperature, and the presence of ligands.The results have shown that the duplex is the moiety that is responsible of the stabilization of the i-motif structure at neutral pH. The T:T base pair, on the contrary, shows little stabilization of the i-motif. From several selected DNA-binding ligands, the G-quadruplex ligand BA41 is shown to interact with the duplex moiety, whereas non-specific interaction and little stabilization has been observed within the i-motif.

Semi-Synthesis of Different Pyranoflavonoid Backbones and the Neurogenic Potential.

Flavonoids and chalcones are known for their manifold biological activities, of which many affect the central nervous system. Pyranochalcones were recently shown to have a great neurogenic potential, which is partly due to a specific structural motif-the pyran ring. Accordingly, we questioned if other flavonoid backbones with a pyran ring as structural moiety would also show neurogenic potential. Different semi-synthetic approaches starting with the prenylated chalcone xanthohumol, isolated from hops, led to pyranoflavanoids with different backbones. We identified the chalcone backbone as the most active backbone with pyran ring using a reporter gene assay based on the promoter activity of doublecortin, an early neuronal marker. Pyranochalcones therefore appear to be promising compounds for further development as a treatment strategy for neurodegenerative diseases.

Thiol‐ene Reaction as Reversible Covalent Bond for the Design of Shape‐Memory Polymers

AbstractBesides a stable phase, shape‐memory polymers require an additional switchable moiety. In addition to thermal transitions and supramolecular interactions, these units can also be based on covalent bonds. Herein, the use of the reversible thiol‐ene reaction as reversible cross‐linker for the design of shape‐memory polymers is demonstrated. A facile route to polymer networks with a thiol‐ene acceptor and a comonomer (butyl methacrylate or 2‐ethylhexyl methacrylate) cross‐linked by dithiols is introduced. The thermal and mechanical properties of the resulting polymers are characterized in detail. Hereby, the polymers feature excellent shape‐memory behavior with fixity and recovery rates above 90%. This study shows that the thiol‐ene cross‐linker can function as both, the stable and the switchable structural moiety rendering the usage of a covalent cross‐linker unnecessary. This partial reversibility can also be proven by temperature‐depending Raman spectroscopy.

SiCO Ceramics as Storage Materials for Alkali Metals/Ions: Insights on Structure Moieties from Solid-State NMR and DFT Calculations.

Polymer-derived silicon oxycarbide ceramics (SiCO) have been considered as potential anode materials for lithium- and sodium-ion batteries. To understand their electrochemical storage behavior, detailed insights into structural sites present in SiCO are required. In this work, the study of local structures in SiCO ceramics containing different amounts of carbon is presented. 13 C and 29 Si solid-state MAS NMR spectroscopy combined with DFT calculations, atomistic modeling, and EPR investigations, suggest significant changes in the local structures of SiCO ceramics even by small changes in the material composition. The provided findings on SiCO structures will contribute to the research field of polymer-derived ceramics, especially to understand electrochemical storage processes of alkali metal/ions such as Na/Na+ inside such networks in the future.

Design, synthesis, structural characterization and computational studies of new class of dispirooxindolopyrrolidine embedded chromanone hybrid heterocycles

Synthesis of a new class of heterocyclic hybrid embedding spirooxindole, pyrrolidine and chromanone structural moieties was achieved in excellent yield using an intermolecular [3+2]-cycloaddition cascade reaction protocol. The synthesized spiropyrrolidines were unambiguously determined by spectroscopic analysis and the stereo- and regiochemistry of the cycloadducts were undoubtably assigned by single crystal X-ray diffraction analysis. Structural features of the compounds were examined by using X-ray crystallographic studies. The molecular packing was defined by Hirshfeld surface analysis. Furthermore, the structure and reactivity of the synthesized dispiropyrrolidines were investigated by density functional theory (DFT) calculations.

Promoting CO2 Dynamic Activation via Micro-Engineering Technology for Enhancing Electrochemical CO2 Reduction.

Optimizing the coordination structure and microscopic reaction environment of isolated metal sites is promising for boosting catalytic activity for electrocatalytic CO2 reduction reaction (CO2 RR) but is still challenging to achieve. Herein, a newly electrostatic induced self-assembly strategy for encapsulating isolated Ni-C3 N1 moiety into hollow nano-reactor as I-Ni SA/NHCRs is developed, which achievesFECO of 94.91% at -0.80V, the CO partial current density of ≈-15.35mA cm-2 , superior to that with outer Ni-C2 N2 moiety (94.47%, ≈-12.06mA cm-2 ), or without hollow structure (92.30%, ≈-5.39mA cm-2 ), and high FECO of ≈98.41% at 100mA cm-2 in flow cell. COMSOL multiphysics finite-element method and density functional theory (DFT) calculation illustrate that the excellent activity for I-Ni SA/NHCRs should be attributed to the structure-enhanced kinetics process caused by its hollow nano-reactor structure and unique Ni-C3 N1 moiety, which can enrich electron on Ni sites and positively shift d-band center to the Fermi level to accelerate the adsorption and activation of CO2 molecule and *COOH formation. Meanwhile, this strategy also successfully steers the design of encapsulating isolated iron and cobalt sites into nano-reactor, while I-Ni SA/NHCRs-based zinc-CO2 battery assembled with a peak power density of 2.54mW cm--2 is achieved.

Novel thienocycloalkylpyridazinones as useful scaffolds for acetylcholinesterase inhibition and serotonin 5-HT6 receptor interaction

A library of eighteen thienocycloalkylpyridazinones was synthesized for human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) inhibition and serotonin 5-HT6 receptor subtype interaction by following a multitarget-directed ligand approach (MTDL), as a suitable strategy for treatment of Alzheimer’s disease (AD). The novel compounds featured a tricyclic scaffold, namely thieno[3,2-h]cinnolinone, thienocyclopentapyridazinone and thienocycloheptapyridazinone, connected through alkyl chains of variable length to proper amine moieties, most often represented by N-benzylpiperazine or 1-(phenylsulfonyl)-4-(piperazin-1-ylmethyl)-1H-indole as structural elements addressing AChE and 5-HT6 interaction, respectively. Our study highlighted the versatility of thienocycloalkylpyridazinones as useful architectures for AChE interaction, with several N-benzylpiperazine-based analogues emerging as potent and selective hAChE inhibitors with IC50 in the 0.17–1.23 μM range, exhibiting low to poor activity for hBChE (IC50 = 4.13–9.70 μM). The introduction of 5-HT6 structural moiety phenylsulfonylindole in place of N-benzylpiperazine, in tandem with a pentamethylene linker, gave potent 5-HT6 thieno[3,2-h]cinnolinone and thienocyclopentapyridazinone-based ligands both displaying hAChE inhibition in the low micromolar range and unappreciable activity towards hBChE. While docking studies provided a rational structural explanation for AChE/BChE enzyme and 5-HT6 receptor interaction, in silico prediction of ADME properties of tested compounds suggested further optimization for development of such compounds in the field of MTDL for AD.

The reliable predicting refractive index for diverse polymers only from structural moieties in repeating unit structures

The refractive index (RI) of polymers is used to understand polymers' behavior in the optical wavelength range, which is essential for designing optical devices. In contrast to available Quantitative Structure-Property Relationship (QSPR) approaches which need complex descriptors, this work introduces a simple method for predicting logRIof polymers based on elemental composition in repeating unit structures as well as two correcting structural parameters. The largest available experimental data of 221 diverse organic polymers are used to derive and test the new model by considering different statistical parameters as well as internal and external validations. Reliably the novel method is compared with the calculated outputs of four QSPR models. The value of Root Mean Square Error (RMSE) of the new model for the training set containing 154 polymers is 0.00623, which is smaller than four QSPR models, i.e., 0.00694, 0.00680, 0.00685, and 0.00691. RMSE values of the test set including 67 polymers also have the same trend, i.e., 0.00621 versus 0.00695, 0.00654, 0.00644, and 0.00640.

Terpene-Containing Analogues of Glitazars as Potential Therapeutic Agents for Metabolic Syndrome.

Metabolic syndrome is a complex of abnormalities involving impaired glucose and lipid metabolism, which needs effective pharmacotherapy. One way to reduce lipid and glucose levels associated with this pathology is the simultaneous activation of nuclear PPAR-alpha and gamma. For this purpose, we synthesized a number of potential agonists based on the pharmacophore fragment of glitazars with the inclusion of mono- or diterpenic moiety in the molecular structure. The study of their pharmacological activity in mice with obesity and type 2 diabetes mellitus (C57Bl/6Ay) revealed one substance that was capable of reducing the triglyceride levels in the liver and adipose tissue of mice by enhancing their catabolism and expressing a hypoglycemic effect connected with the sensitization of mice tissue to insulin. It has also been shown to have no toxic effects on the liver.

Novel fluorocurcuminoid-BF2 complexes and their unlocked counterparts as potential bladder anticancer agents – synthesis, physicochemical characterization, and in vitro anticancer activity

Low efficiency of anticancer drugs and their toxicity in normal tissues has motivated further study on safe and effective modern anticancer agents. In the presented study, the design and synthesis of a library of 14 fluorinated curcumin (F-CUR) derivatives and their F-CUR-BF2 adducts are presented. Chemical modifications of curcumin derivatives included the introduction of BF2 unit to the diketone group, as well as the substitutions of one or two fluorine atoms in different positions of the phenyl rings. The obtained compounds were broadly characterized using ESI HRM spectrometry, 1D and 2D NMR techniques (1H, 13C, 19F, HMBC, HSQC and COSY), Fourier transform infrared spectroscopy (FTIR), and melting points. Moreover, the purity of curcumin derivatives was determined using TLC and HPLC. Novel curcumin derivatives were subjected to biological studies against two bladder cancer cell lines 5637 and SCaBER using the MTT assay and then the structure-activity relationship was established.Our study demonstrated that it is the presence of the BF2 moiety in the curcumin derivative structure, which determines the cytotoxic effect on cancer cells as the compounds with unchanged 3,5-diketone unit did not appear active in cancer cells. In addition, higher activities among the studied compounds were observed for curcumin-BF2 adducts with methoxy than with the hydroxy or fluorine group; or for compounds containing one fluorine rather than two fluorine groups. Moreover, it has become evident that the position of substituents relative to each other plays a significant role. To sum up, all BF2 adducts appeared more effective than curcumin, with the most cytotoxic compound belonging to F-CUR-BF2 adducts with 3-fluoro-4-methoxyphenyl groups in its structure and IC50 values of 6.49±0.49 μM and 3.31±0.51 μM after 24h incubation for 5637 and SCaBER cancer cell lines, respectively. The four most active F-CUR-BF2 derivatives and their F-CUR analogs were subjected to stability tests. Based on the stress tests, the susceptibility of these compounds to various environmental factors, such as hydrolytic and oxidizing agents, light, and temperature, were assessed.

Synthetic Strategies Towards and Around the CF3S(O) Structural Motif

Abstract: This account reviews synthetic strategies for constructing and transforming CF3S(O) structural moiety developed during the last decades. Existing paths to the synthesis of CF3S(O)-containing organic molecules are demonstrated. Among these are direct trifluoromethanesulfinylation reactions, oxidation of compounds having CF3S function, substitutive trifluoromethylation reactions of sulfinic acid halides and esters, and rearrangement reactions. The reactivity and substituent modification procedures are covered. Also included are sections on the synthetic application of the CF3S(O)-bearing molecules for the design of biologically important molecules and synthesis of other organofluorine compounds.

Locating anionic hydrogen in Ba3(Yb,Lu)2O5H2: A combined approach of X-ray diffraction, crystal chemistry, and DFT calculations

By a combination of x-ray diffraction, structural chemistry, and DFT calculations, the presence and location of anionic hydrogen in the two new, layered lanthanide oxyhydrides, Ba3Ln2O5H2 (Ln ​= ​Yb, Lu) is inferred. Single crystals of the compounds have been synthesized from a molten barium flux with the addition of small amounts of BaH2. These phases crystallize in space group I4/mmm (#139, Z ​= ​2) with lattice parameters a ​= ​4.3336(2) Å and c ​= ​22.7197(6) Å, and a ​= ​4.3291(1) Å and c ​= ​22.597(1) Å, respectively. The Ba3Ln2O5H2 phases comprise two different structural moieties: a perovskite double layer of stoichiometry Ba2Ln2O5H− formed by corner-connected LnO5 tetragonal bi-pyramids with a terminating hydrogen anion, and a puckered rocksalt-type (BaH)+ layer that is stretched along the c-axis. DFT calculations were used to arrive at hydrogen positions that minimize energy and are consistent with structural chemistry principles. Furthermore, the calculations show that the valence band edge is dominated by oxygen 2p orbitals with hydrogen 1s states admixed. The conduction band is formed by barium 5d-orbitals and Lu (Yb) 5d-orbitals. These are characteristics of materials with anionic H−. These new phases are isostructural with the Ba3Ln2O5Cl2 (Ln ​= ​Gd–Lu) family of compounds with the chlorine atom in the same apical position as the hydrogen atom. Steric effects limit the size of the lanthanide ion for Ba3Ln2O5H2.

Familiarizing Undergraduate Students with Advanced Mass Spectrometry Techniques: An Example of Detailed Lipid Structure Characterization

This study highlights the importance of incorporating modern mass spectrometry techniques into undergraduate education. By focusing on the structure-characterizing capability of MS, students are able to gain hands-on experience with cutting-edge techniques and better understand how MS can be used to solve real-world problems. The three-step lipid structure analysis strategy presented in the study is a great example of this, as it allows students to understand the process of lipid analysis from headgroup identification to the determination of fatty acyl chain composition and the location of C═C double bonds. The use of chemical derivatization to preactivate a structural moiety for MS/MS analysis is also emphasized in the study. This provides students with a deeper understanding of the limitations of MS/MS analysis and how chemical modifications can be used to overcome these limitations. The demonstration of a [2 + 2] photochemical reaction to locate a C═C in unsaturated lipids is a practical example of this concept. Overall, this study supports the idea that incorporating advanced research techniques into undergraduate education can not only enhance students' understanding of scientific instruments but also promote their interests in research and innovation.

Anti-Inflammatory Therapeutic Mechanisms of Natural Products: Insight from Rosemary Diterpenes, Carnosic Acid and Carnosol.

Carnosic acid (CA) and carnosol (CAR) are two major diterpenes of the rosemary plant (Rosmarinus officinalis). They possess a phenolic structural moiety and are endowed with the power to remove cellular reactive oxygen species (ROS) either through direct scavenging reaction or indirectly through upregulation of antioxidant defences. Hand in hand with these activities are their multiple biological effects and therapeutic potential orchestrated through modulating various signalling pathways of inflammation, including the NF-κB, MAPK, Nrf2, SIRT1, STAT3 and NLRP3 inflammasomes, among others. Consequently, they ameliorate the expression of pro-inflammatory cytokines (e.g., TNF-α, IL-1 and IL-6), adhesion molecules, chemokines and prostaglandins. These anti-inflammatory mechanisms of action as a therapeutic link to various effects of these compounds, as in many other natural products, are scrutinised.