Complex Moieties Research Articles

4N donor atoms moiety of transition metal complexes of a Schiff base ligand: Synthesis, characterization and biological activities study

Prepared new Schiff base ligand [H2L] with 4N donor atoms moiety by reacting amine derivative of o-phenylenediamine hydrazide moiety with benzaldehyde. Co(II), Ni(II), Cu(II) and Zn(II) of the new Schiff base were prepared by using a molar ratio of ligand: metal as (1:1). The structure of the Schiff base and the prepared complex was determined by 1H NMR, UV–Vis, IR, Mass spectrometry and molar conductivity. The thermal stability of the complexes had been studied by TGA. The spectral statement displays that the ligand behaves as bidentate ligand. On the basis of the spectral studies, reveal that an octahedral geometry had been assigned for all complexes. The Anti-proliferative effect was screened against human hepatocellular liver carcinoma cell line (HepG2) and antimicrobial activity had been inspected. Result points that complexes demonstrate the increase cytotoxicity in proliferation to cell lines as compared to free ligand.

An insight into the supramolecular interactions in two linear polyvanadates

Two polymeric [VO3]nn− metavanadate chain complexes have been synthesized and characterized by spectral and elemental analysis. The X-ray data of only complex 2 has been reported in this work. Both the complexes have a linear vanadate chain, countered by appropriately charged organic amine moieties. The simplest units of the chains contain a linear [V3O9]3− and [V2O6]2− anionic moieties in complexes 1 and 2, respectively. The charge neutralizing cationic counterparts are triprotonated tren {tris(2-aminoethyl)amine} and a diprotonated N-ethylethylenediamine in complexes 1 and 2, respectively. Complex 2 is unique in the sense that its crystal lattice contains the divanadate [V2O6]2− repeat unit and protonated N-ethylethylenediamine as the charge compensating and space filling moiety which is not reported in any other literature till now. The individual units are assembled to form a 2D supramolecular network. DFT calculations (PBE0-D3/def2-TZVP) have been used in combination to QTAIM and NCI plot computational tools to analyze the strong N–H···O charge assisted hydrogen bonding interactions in both complexes. Phenoxazinone synthase like activity (i.e. oxidative conversion of o-aminophenol to 2-aminophenoxazine-3-one) of complex 2 was evaluated.

Lipid-based Nano-phytomedicines for Disease Treatment and Theranostic Applications

: Several lipid-based nanophytomedicines for illustrations, solid lipid nanoparticles, nanocomposites, lipid carriers, phytosomes, cubosomes, nanoemulsions, microcapsules, ethosomes, etc., are exploited to enhance the efficacy and safety of various bioactive phytochemicals with respect to their delivery to therapeutic target sites. Less lipid solubility, week stability, complex moiety, and inadequate metabolism in the gut are approximate of the serious problems of phytomedicine that have been emphasized extremely. In addition, these help design therapeutically efficacious and active nanophytomedicines. Disease diagnosis and compound imaging have also become important applications of nano-phytomedicine now. The aim of this review is to provide the current progress of lipid-based nanophytomedicines for the treatment of various life-threatening diseases and their theranostic applications.

Superalkali-doped borazine and lithiated borazine complexes: diffuse excess electron and large first-hyperpolarizability.

A number of superalkali (M3O / M3S; M = Li, Na, K)-doped borazine and hexalithio borazine complexes are considered for the theoretical study of their electronic structure and quadratic polarizability. Electron-rich O/S atom of superalkali species remains very close to one boron atom of the ring through non-covalent interaction. The first-hyperpolarizability increases rather significantly upon superalkali doping. The chosen complexes possess diffuse excess electron which is located on the superpalkali moiety of borazine complexes and at the ring site of lithiated borazines. First-hyperpolarizability of M3O(S)@B3N3Li6 complexes are significantly larger than that of the corresponding M3O(S)@B3N3H6 complexes. The magnitude of first-hyperpolarizability of Li3S@B3N3Li6 is larger than that of Li3S@B3N3H6 by about three orders of magnitude.

Coordination behavior of PPh2{C6H4[CH2N(CH2CH2)2O]-2}: Case study CdCl2[PPh2{C6H4[CH2N(CH2CH2)2O]-2}

Abstract The reaction between CdCl2 and PPh2{C6H4 [CH2N(CH2CH2)2O]-2} (1) in a 1:1 molar ratio resulted in the cadmium(II) complex CdCl2[PPh2{C6H4[CH2N(CH2CH2)2O]-2}] (2). The complex 2 was characterized in solution by NMR spectroscopy (1H, 13C, and 31P). Single-crystal X-ray diffraction studies revealed no intramolecular N→P interaction in 1. The phosphane ligand behaves as a P,N chelating moiety in the cadmium complex 2, thus resulting in a species containing distorted tetrahedral environments around cadmium and phosphorus. Short intermolecular interactions CH‧‧‧π aryl and CH‧‧‧O in 1 and CH‧‧‧π aryl and CH‧‧‧Cl in 2 resulted in supramolecular networks.

Synthesis, Characterization and Crystal Structures of Zwitterionic Triazolato Complexes by Reaction of a Ruthenium Azido Complex with Excess Ethyl Propiolate

The synthesis and structures of two novel zwitterionic ruthenium triazolato complexes are reported. The treatment of the ruthenium azido complex [Ru]-N3 (1, [Ru] = (η5-C5H5)(dppe)Ru, dppe = Ph2PCH2CH2PPh2) with an excess of ethyl propiolate in CHCl3 or CH2Cl2 under ambient conditions for 15 days results in the formation of a mixture of the Z- and E-forms of N(1)-bound ruthenium 3-ethylacryl-4-carboxylate-3H-1,2,3-triazolato complexes [Ru]N3(CH=CHCO2Et)C2H(CO2) (Z-3) and (E-3) in a ratio of ca. 5:2. The structures of E-3 and Z-3 were confirmed by single-crystal X-ray diffraction analysis and fully characterized by 1H, 31P, 13C NMR and IR spectroscopy, mass spectrometry, and elemental analysis. The negatively charged carboxylate moieties of the zwitterionic ruthenium triazolato complexes Z-3 and Z-3 are highly nucleophilic and reactive toward a variety of electrophiles, making Z-3 and Z-3 potential starting materials for the development of biologically active 1,2,3-triazole derivatives.

Glycosylation Profiling as a Biomarker of Suboptimal Health Status for Chronic Disease Stratification.

WHO defines health as "a state of complete physical, mental, and social well-being and not merely the absence of disease or infirmity." We coined and defined suboptimal health status (SHS) as a subclinical, reversible stage of the pre-chronic disease. SHS is a physical state between health and disease, characterized by health complaints, general weakness, chronic fatigue, and low energy levels. We have developed an instrument to measure SHS, Suboptimal Health Status Questionnaire-25 (SHSQ-25), a self-reported survey assessing five health components that has been validated in various ethnical populations. Our studies suggest that SHS is associated with the major components of cardiovascular health and the early onset of metabolic diseases. Besides subjective measure of health (SHS), glycans are conceived as objective biomarkers of SHS. Glycans are complex and branching carbohydrate moieties attached to proteins, participating in inflammatory regulation and chronic disease pathogenesis. We have been investigating the role of glycans and SHS in multiple cardiometabolic diseases in different ethnical populations (African, Chinese, and Caucasian). Here we present case studies to prove that a combination of subjective health measure (SHS) with objective health measure (glycans) represents a window of opportunity to halt or reverse the progression of chronic diseases.

Highly photoluminescent poly(norbornene)s carrying platinum–acetylide complex moieties in their side chains: evaluation of oxygen sensing and TTA–UC

Poly(norbornene)s carrying platinum–acetylide complex moieties change their photoluminescence colors in response to oxygen. The polymers serve as excellent sensitizers of TTA–UC with 9,10-diphenylanthracene.

Synthesis of Platinum-Containing Conjugated Polymers Bearing Optically Active Amide Groups: A Mechanistic Study of Chiral Aggregation

Chirally regulated π-conjugated polymers containing platinum (Pt) complex moieties have great potential as chiroptically functional materials. In this study, novel platinum-containing conjugated po...

Electrochromic Properties of Metallo-Supramolecular Polymers and the Display Device Application

Metallo-supramolecular polymers were synthesized by the complexation of transition metal ions including Fe(II), Ru(II), and Os(II) with ditopic organic ligands such as bisterpyridines. The obtained polymers were easily processed to the film state by spray-coating due to the amorphous nature of polymers. The polymers have specific color such as blue, red, and yellow, based on the metal-to-ligand charge transfer (MLCT) absorption in the complex moieties of polymer. The author and coworkers found reversible electrochromism in the polymer film, triggered by the electrochemical redox of the metal ions in the polymers. We confirmed high durability to the repeated color changes more than 100,000 times. Fe(II)-based metallo-supramolecular polymer (polyFeL1), which was prepared by the 1:1 complexation of Fe(II) ions and bis(terpyridyl)benzene (L1), exhibited high coloration efficiency (263.8 cm2/C). When tris(terpyridyl)benzene (L2) and Fe(II) ions were further added to a polyFeL1 solution, the linear polymer structure of polyFeL1 was hyperbranched. Interestingly, the hyperbranched structure has enhanced the coloration efficiency of the polymer film up to 383.4 cm2/C. We could introduce two metal species (Fe(II) and Ru(II)) in the polymer by simple mixing of Fe(II), Ru(II), and L1 at the molar ratio of 0.5:0.5:1. The obtained heterometallo-supramolecular polymer displayed multi-color electrochromism by changing the applied potential, because the redox potential of Fe(II)/(III) and Ru(II)/(III) are different. We succeeded in fabricating electrochromic devices using the polymers. Owing to the amorphous nature of polymers, flexible electrochromic sheet devices were also fabricated. The nonvolatile display devices with both high durability and abundant color variation will be attractive for wide applications containing smart windows, wearable IoT displays, and digital signages.

Two Anthracene-Based Ir(III) Complexes [Ir(pbt)2(aip)]Cl and [Ir(pbt)2(aipm)]Cl: Relationship between Substituent Group and Photo-oxidation Activity as Well as Photo-oxidation-Induced Luminescence.

Two anthracene-based complexes [Ir(pbt)2(aip)]Cl (1) and [Ir(pbt)2(aipm)]Cl (2) have been synthesized based on the ligands aip = 2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline, aipm = 2-(9-anthryl)-1-methyl-imidazo[4,5-f][1,10]phenanthroline, and pbtH = 2-phenylbenzothiazole in order to explore both the influence of the substituent group R1 (R1 = H in 1 and CH3 in 2) on photo-oxidation activity and photo-oxidation-induced luminescence. Both 1H NMR spectra and ES mass spectra indicate that the anthracene moiety in complex 1 can be oxidized at room temperature upon irradiation with 365 nm light. Thus, this complex shows photo-oxidation-induced turn-on yellow luminescence. Compared to 1, complex 2 incorporates an R1 = CH3 group, resulting in very weak photo-oxidation activity. On the basis of experimental results and quantum chemical calculation, we report the differences between 1 and 2 in both photo-oxidation behavior and the related luminescence modulation and discuss the relationship between photo-oxidation activity and substituent group R1 in these complexes.

Ab initio investigations on the interaction of CO2 and non-metallic superalkalis: structure, stability and electronic properties

Superalkalis are hypervalent species, having lower ionisation energy than alkalis and its strong reducing capabilities can be used in the design of a variety of charge-transfer compounds. The interaction of non-metallic superalkalis such as F2H3, O2H5, and N2H7 with CO2 has been systematically explored using ab initio MP2/6-311++G(d,p) method. We have studied the structural isomers of the resulting superalkali-CO2 complexes and their relative stabilities. We have analyzed their partial charge, spin density, and singly-occupied molecular orbitals’ energy, which reveal the relative strength and charge transfer due to the interaction of CO2 with superalkalis. We notice that this interaction leads to the reduction of CO2, as the structure of CO2 moiety in superalkali-CO2 complexes is bent due to electron transfer from superalkalis. Thus, this study should provide some interesting results on the single-electron reduction of CO2 by non-metallic compounds.

A tetrameric uudd type water cluster encapsulated in a dinuclear vanadium(V) Schiff base complex and its role in the formation of supramolecular assemblies: A joint experimental and theoretical study

A new dinuclear vanadium(V) complex, [(µ-O)2V2O2L2]·4H2O, [where HL = 2-((2-(ethylamino)ethylimino)methyl)-5-(diethylamino)phenol] has been synthesized and subsequently characterized by elemental and spectral studies. Structure of the complex has been confirmed by single crystal X-ray diffraction study. The four lattice water molecules in the crystal structure are assembled to form a tetrameric water cluster (W4), stabilized via hydrogen bonding interactions. These clusters further interconnect with the complex moiety to generate a 1D supramolecular chain of the complex in the solid state. The interaction energies and the possible cooperativity effects have been studied using DFT calculations and the MEP surface analysis.

Synthesis, characterization, and evaluation of biological activities of new 4′‐substituted ruthenium (II) terpyridine complexes: Prospective anti‐inflammatory properties

The synthesis and characterization of Ru (II) terpyridine complexes derived from 4′ functionalized 2,2′:6′,2″‐terpyridine (tpy) ligands are reported. The heteroleptic complexes comprise the synthesized ligands 4′‐(2‐thienyl)‐ 2,2′:6′,2″‐terpyridine) or (4′‐(3,4‐dimethoxyphenyl)‐2,2′:6′,2″‐terpyridine and (dimethyl 5‐(pyrimidin‐5‐yl)isophthalate). The new complexes [Ru(4′‐(2‐thienyl)‐2,2′:6′,2″‐terpyridine)(5‐(pyrimidin‐5‐yl)‐isophthalic acid)Cl2] (9), [Ru(4′‐(3,4‐dimethoxyphenyl)‐2,2′:6′,2″‐terpyridine)(5‐(pyrimidin‐5‐yl)‐isophthalic acid)Cl2] (10), and [Ru(4′‐(2‐thienyl)‐2,2′:6′,2″‐terpyridine)(5‐(pyrimidin‐5‐yl)‐isophthalic acid)(NCS)2] (11) were characterized by 1H‐ and 13C‐NMR spectroscopy, C, H, N, and S elemental analysis, UPLC‐ESI‐MS, TGA, FT‐IR, and UV‐Vis spectroscopy. The biological activities of the synthesized ligands and their Ru (II) complexes as anti‐inflammatory, antimicrobial, and anticancer agents were evaluated. Furthermore, the toxicity of the synthesized compounds was studied and compared with the standard drugs, namely, diclofenac potassium and ibuprofen, using hemolysis assay. The results indicated that the ligands and the complex 9 possess superior anti‐inflammatory activities inhibiting albumin denaturation (89.88–100%) compared with the standard drugs (51.5–88.37%) at a concentration of 500 μg g−1. These activities were related to the presence of the chelating N‐atoms in the ligands and the exchangeable chloro‐ groups in the complex. Moreover, the chloro‐ and thiophene groups in complex 9 produce a higher anticancer activity compared with its isothiocyanate derivative in the complex 11 and the 3,4‐dimethoxyphenyl moiety in complex 10. Considering the toxicity results, the synthesized ligands are nontoxic or far less toxic compared with the standard drugs and the metal complexes. Therefore, these newly synthesized compounds are promising anti‐inflammatory agents in addition to their moderate unique broad antimicrobial activity.

2-(Substituted amino)-8-azachromones from 4,6-Diaryl-2-pyridones: A Synthetic Strategy toward Compounds of Broad Structural Diversity.

3-Acetoacetyl-4,6-diaryl-2-pyridones are synthesized in three steps from chalcones and then condense with carbon disulfide to afford 8-azachromones containing a methylthio group at C2. This leaving group offers an entry point for the insertion of more complex moieties via nucleophilic substitution. For this purpose, N-nucleophiles are explored according to their positions in the Mayr's nucleophilicity scale (N parameter), and three main classes are distinguished depending on whether the substitution takes place from their neutral forms, from their deprotonated anionic forms, or under nucleophilic catalysis. A broad range of primary and secondary amines may be inserted by this method, including enantiomerically pure amino acids, enabling us to explore structural diversity.

Synergistic Effect of Pendant N Moieties for Proton Shuttling in the Dehydrogenation of Formic Acid Catalyzed by Biomimetic IrIII Complexes.

Formic acid (FA) is among the most promising hydrogen storage materials. The development of efficient catalysts for the dehydrogenation of FA via molecular-level control and precise tuning remains challenging. A series of biomimetic Ir complexes was developed for the efficient dehydrogenation of FA in an aqueous solution without base addition. A high turnover frequency of 46510 h-1 was achieved at 90 °C in 1 m FA solution with complex 1 bearing pendant pyridine. Experimental and mechanistic studies revealed that the integrated pendant pyridine and pyrazole moieties of complex 1 could act as proton relay and facilitate proton shuttling in the outer coordination sphere. This study provides a new strategy to control proton transfer accurately and a new principle for the design of efficient catalysts for FA dehydrogenation.

Nanoformulated Single-Stranded RNA-Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen-Presenting Cells.

As agonists of TLR7/8, single-stranded RNAs (ssRNAs) are safe and promising adjuvants that do not cause off-target effects or innate immune overactivation. However, low stability prevents them from mounting sufficient immune responses. This study evaluates the adjuvant effects of ssRNA derived from the cricket paralysis virus intergenic region internal ribosome entry site, formulated as nanoparticles with a coordinative amphiphile, containing a zinc/dipicolylamine complex moiety as a coordinative phosphate binder, as a stabilizer for RNA-based adjuvants. The nanoformulated ssRNA adjuvant was resistant to enzymatic degradation in vitro and in vivo, and that with a coordinative amphiphile bearing an oleyl group (CA-O) was approximately 100 nm, promoted effective recognition, and improved activation of antigen-presenting cells, leading to better induction of neutralizing antibodies following single immunization. Hence, CA-O may increase the efficacy of ssRNA-based adjuvants, proving useful to meet the urgent need for vaccines during pathogen outbreaks.

Nanoformulated Single‐Stranded RNA‐Based Adjuvant with a Coordinative Amphiphile as an Effective Stabilizer: Inducing Humoral Immune Response by Activation of Antigen‐Presenting Cells

AbstractAs agonists of TLR7/8, single‐stranded RNAs (ssRNAs) are safe and promising adjuvants that do not cause off‐target effects or innate immune overactivation. However, low stability prevents them from mounting sufficient immune responses. This study evaluates the adjuvant effects of ssRNA derived from the cricket paralysis virus intergenic region internal ribosome entry site, formulated as nanoparticles with a coordinative amphiphile, containing a zinc/dipicolylamine complex moiety as a coordinative phosphate binder, as a stabilizer for RNA‐based adjuvants. The nanoformulated ssRNA adjuvant was resistant to enzymatic degradation in vitro and in vivo, and that with a coordinative amphiphile bearing an oleyl group (CA‐O) was approximately 100 nm, promoted effective recognition, and improved activation of antigen‐presenting cells, leading to better induction of neutralizing antibodies following single immunization. Hence, CA‐O may increase the efficacy of ssRNA‐based adjuvants, proving useful to meet the urgent need for vaccines during pathogen outbreaks.

Interaction of cobalt and iron hydroperoxo bleomycin with deoxyribonucleic acid (DNA): Dynamic vs. electronic structure considerations

Classical molecular mechanics and quantum mechanical dynamics calculations of iron and cobalt hydroperoxo adducts of bleomycin with deoxyribonucleic acid (DNA) yield structures in reasonable agreement with the experimentally-known Co structures. The hydroxyl (OH) group of the metal-bound hydroperoxide is predicted to reside very close to a deoxyribose proton in the Co-hydroperoxo-DNA adduct (in agreement with experiment) as well as in the ferric counterpart (for which no structural data is available from experiments). According to density functional theory calculations, this sterical arrangement leads to facile insertion of the peroxide OH into the sugar within the Fe(III) but not in the Co(III)-hydroperoxo-bleomycin-DNA complex. However, experiments reveal that the peroxo oxygen is in fact not inserted into the product – at odds with the quantum mechanical calculations. On the other hand, the computed dynamics of the peroxide-sugar distance involve occasional movement of the peroxide ~1.5 Å further away from the CH bond, providing an opportunity for Fe(III)O-OH bond cleavage without immediately trapping the departing OH onto the deoxyribose. Also, while the peroxide moiety in the DNA-bleomycin complex is on average well shielded from the solvent, the dynamics calculations reveal occasional opening of this shielding on nanosecond timescales; individual snapshots are identified, where water molecules from the solvent are in direct contact with the iron-bound hydroperoxide in the bleomycin-DNA complex. Therefore, the general picture provided by molecular dynamics simulations is one where the oxygen–oxygen bond is initially cleaved to generate a high-valent intermediate, which can oxidize the deoxyribose in an outer-sphere manner

Complex Generic Products: Insight of Current Regulatory Frameworks in US, EU and Canada and the Need of Harmonisation.

The regulatory agencies all over the world have defined the pathway and regulations for the approval of simple small-molecule generics. In addition, the agencies are striving to form perspicuous regulatory frameworks for the approval of biosimilars. In this view, there are no defined regulations for the approval of complex generics, also known as non-biological complex drugs (NBCDs). Complex drugs are large, highly complex and synthetic moieties and are made of complex active substances but are different from biologics product. Regulatory frameworks being adopted for complex generics today are questionable and ambiguous. The market for complex generics is huge and there are fewer generic competitors in this area. In addition, the cost of bringing such generics into the market is high. Since the complex generics are largely used for chronic and life-threatening diseases and the competition is less, generic players show high interest in this segment. Thus, there is a need for a well-defined pathway and guidance documents for the authorization of generic versions of complex drug products. The article focuses on the regulatory frameworks currently adopted by US, EU and Canada for bringing complex generics into the market. It also describes on the regulatory disparities existing among the three agencies in the light of complex generics.