Anisotropic exchange in a tetranuclear CoII complex

Very high-frequency (50–715 GHz) electron paramagnetic resonance (EPR) studies of the tetranuclear Co^II complex [Co(hmp)(dmb)Cl]₄ (1), where dmb is 3,3-dimethyl-1-butanol and hmp^? is the monoanion of 2-hydroxy-methylpyridine, reveal the presence of significant zero-field-splitting (ZFS) within the ground state spin multiplet. Meanwhile, low-temperature hysteresis measurements of 1 (and related Co^II₄ complexes) provide evidence for slow magnetization relaxation, suggesting that it could be a single-molecule magnet (SMM). However, EPR studies of a Zn analog of 1, doped with a small quantity of Co^II, show the ground state of the Co^II ions to be an effective spin S′ = 1/2 Kramers doublet with a highly anisotropic g-tensor. The question then arises as to the origin of the ZFS within the ground state spin multiplet of 1, as well as the slow magnetization relaxation. Here, we consider the effect of anisotropic exchange interactions between the effective spin S′ = 1/2 Kramers ions within the tetranuclear complex. Such exchange anisotropy arises naturally when one treats the ground state of high-spin Co^II as a Kramers doublet. Our model provides an explanation for the ZFS in the ground state observed via EPR, and can also account for qualitative features observed through magnetic measurements.     

Cobalt complexes supported by salicylichydrazono derivative ligands and various coordination solvents

We report the synthesis and molecular solid-state structures of five novel Co^II and Co^III mononuclear complexes supported by the 2-salicyloylhydrazono-1,3-dithiolane (L1) and 2-salicyloylhydrazono-1,3-dithiane (L2) ligands. Moreover, one novel diamagnetic μ-oxo dinuclear Co^III complex [Co^III₂(HL)₄(μ-O)₂] supported by the ligand L1 was stabilized and characterized. Crystal structure of the supporting ligand L2 was also determined.     

Can Artemisia herba-alba Be Useful for Managing COVID-19 and Comorbidities?

The focus of this roadmap is to evaluate the possible efficacy of Artemisia herba-alba Asso. (Asteraceae) for the treatment of COVID-19 and some of its symptoms and several comorbidities using a combination of in silico (molecular docking) studies, reported ethnic uses, and pharmacological activity studies of this plant. In this exploratory study, we show that various phytochemicals from Artemisia herba-alba can be useful against COVID-19 (in silico studies) and for its associated comorbidities. COVID-19 is a new disease, so reports of any therapeutic treatments against it (traditional or conventional) are scanty. On the other hand, we demonstrate, using Artemisia herba-alba as an example, that through a proper search and identification of medicinal plant(s) and their phytochemicals identification using secondary data (published reports) on the plant’s ethnic uses, phytochemical constituents, and pharmacological activities against COVID-19 comorbidities and symptoms coupled with the use of primary data obtained from in silico (molecular docking and molecular dynamics) studies on the binding of the selected plant’s phytochemicals (such as: rutin, 4,5-di-O-caffeoylquinic acid, and schaftoside) with various vital components of SARS-CoV-2, it may be possible to rapidly identify plants that are suitable for further research regarding therapeutic use against COVID-19 and its associated symptoms and comorbidities.     

Synthesis,X-ray structure and magnetic properties of a unusual transition Co(II) complex with polychlorotriphenylmethyl radicals

A new cobalt(II) complex with a polychlorotriphenylmethyl radical ligand properly functionalized with a carboxylate group (PTMMC⁻), [Co(PTMMC)₂(py)₂(H₂O)₂]·[Co(PTMMC) (py)₃(H₂O)(Cl)]₂·2py·2THF (3), has been synthesized and characterized including single-crystal X-ray diffraction. The structure of 3 consists of two different Co(II) units, [Co(PTMMC)₂(py)₂(H₂O)₂] (3A) and [Co(PTMMC) (py)₃(H₂O)(Cl)] (3B), which cocrystallize together with two molecules of pyridine and two molecules of THF. Its magnetic behaviour shows the presence of antiferromagnetic interactions between the PTMMC radicals and the Co(II) ions. The experimental data was fitted to a magnetic model based on the sum of a linear trimer (S_R1…S_Co…S_R2) and a dimer (S_Co…S_R3) to give a Co(II)-radical exchange coupling of J/K_B=−16.0 K for both complexes.     

Crotocaudin; a rearranged labdane type norditerpene from Croton caudatus geisel

The structure and stereochemistry of crotocaudin, a new norditerpene occurring as a minor constituent in Crotoncaudatus Geisel (Euphorbiaceae) have been established as ent-8S,10S-15,16-epoxy-19-norcleroda-4,11,13(16), 14-tetraene 18,6S: 20,12-diolactone 7 from the detailed studies of ¹H NMR spectra using lanthanide shift reagents, decoupling experiments and chemical reactions. The congener, teucvidin, ent-10S-15,16-epoxy-19-norcleroda-4,13(16), 14-triene-18,6S: 20,12R-diolactone 1 was obtained as a major component besides several triterpenoids viz taraxerone 2, taraxerol 3 and taraxeryl acetate 4. ¹³C NMR and ¹H NMR spectra and a few novel reactions of teucvidin and its conversion to teucvin, ent-(6R,12R)-15,16-epoxy-19-nor-9,4-friedolabda-4,13(16),14-triene-18,6:20, 12-diolactone 6 are also reported.     

Developing potent BTKC481S PROTACs for ibrutinib-resistant malignant lymphoma

Ibrutinib is a first-line treatment drug for B-cell malignancies. However, resistance to ibrutinib has been reported due to BTK^C481S mutation. Although PROTAC strategy is expected to overcome this clinical resistance, it has limitations such as large molecular weight and moderate bioactivity, which restrict its potential clinical application. Herein, we report a new type of potent BTK^C481S-targeting PROTAC degrader. Through design, computer-assisted optimization and SAR studies, we have developed a representative BTK^C481S degrader L6 with a much smaller molecular weight and improved solubility. Notably, L6 demonstrates better BTK degrading activity and lower IC₅₀ value in ibrutinib-resistant cell line than the first-generation BTK degrader P13I. Optimization strategy of L6 provides a general approach in the development of PROTACs targeting BTK and other proteins for future study.     

Synthesis of two (S)-indoline-based chiral auxiliaries and their use in diastereoselective alkylation reactions

Two chiral auxiliaries, 2-[(S)-indolin-2-yl]propan-2-ol 1a and (S)-2-(2-methoxypropan-2-yl)indoline 1b, were synthesised from enantiomerically pure (S)-indoline-2-carboxylic acid 3. High diastereoselectivities in alkylations of enolates of the propanoylamides derived from the two auxiliaries are presented. Surprisingly, both auxiliaries induced the same selectivity at the newly created stereogenic centre. The benzyl bromide and n-butyl iodide alkylation reactions showed diastereomeric ratios that were moderate (81:19) to very good (96:4) and with very good yields (86–98%). When LiCl was used as an enolate coordinating agent, in the benzylation of the enolate from propanoylated auxiliary 1a, a very high crude diastereomeric ratio was obtained (99.7:0.3).     

Rational synthesis of hexanuclear metallacycles by alkylation reactions of an S-bridged CoIIIPdIICoIII trinuclear complex containing non-binding thiolato groups

The reaction of an S-bridged Co^IIIPd^IICo^III trinuclear complex containing two non-bridging thiolato groups, [Pd{Co(aet)₃}₂]²⁺ (aet = 2-aminoethanethiolate), with o-dibromoxylene (o-xylBr₂) in water produced a cyclic Co^III₄Pd^II₂ hexanuclear complex, [{Co₂Pd(aet)₄}₂(o-L)₂]⁸⁺ ([1]⁸⁺; o-L = o-bis(2-aminoethylthiomethyl)benzene), in which two Co^IIIPd^IICo^III trinuclear units are linked by two o-xyl²⁺ moieties through C–S bonds. A similar cyclic Co^III₄Pd^II₂ complex, [{Co₂Pd(aet)₄}₂(m-L)₂]⁸⁺ ([2]⁸⁺; m-L = m-bis(2-aminoethylthiomethyl)benzene), bearing a relatively large cavity that accommodates water molecule(s), was synthesized by the reaction of [Pd{Co(aet)₃}₂]²⁺ with m-dibromoxylene (m-xylBr₂) in water. While [1]⁸⁺ afforded only the racemic (Δ₄/Λ₄) isomer, both the racemic ([2a]⁸⁺; Δ₄/Λ₄) and the meso ([2b]⁸⁺; Δ₂Λ₂) isomers were formed for [2]⁸⁺. In addition, the meso [2b]⁸⁺ was found to exist as a mixture of two diastereomers, (Δ_S)₂(Λ_R)₂ and (Δ_SΔ_R)(Λ_RΛ_S), which arise from the difference in chiral configurations (R and S) of asymmetric sulfide S atoms, while the racemic [1]⁸⁺ and [2a]⁸⁺ existed as a pair of enantiomers, (Δ_S)₄ and(Λ_R)₄, which were optically resolved. The complexes obtained were characterized on the basis of electronic absorption, CD, and NMR spectroscopies, along with single crystal X-ray analyses.     

A stable organic triradical with truncated π-conjugation as a model for single-component organic molecule-based ferrimagnetics

As a novel molecular design for genuinely organic molecule-based ferrimagnets, we have proposed a strategy of ‘single-component ferrimagnetics.’ When a π-biradical with an S=1 ground state and a π-monoradical with S=1/2 are united by σ-bonds, the π-conjugation between the biradical and the monoradical moieties should be truncated in the resultant triradical. This gives magnetic degrees of freedom for both S=1 and S=1/2 in the single molecule, serving as a building block for organic molecular ferrimagnets. We have designed and synthesized a triradical, 2,2,6,6-tetramethyl-pipelidine-1-N-oxyl-4-carboxylic acid 2,4-bis(1-oxyl-3-oxido-4,4,5,5-tetramethyl-2-imidazolin-2-yl)-phenyl ester (2) as a model compound for single-component ferrimagnetics. Solution-phase ESR spectra from 2 are explained by a perturbation treatment assuming that the exchange interaction within the biradical moiety is much larger than those between the biradical and the monoradical moieties, which is suitable for single-component ferrimagnetics. From susceptibility measurements for a cyclohexane-substituted biradical, cyclohexane carboxylic acid 2,4-bis(1-oxyl-3-oxido-4,4,5,5-tetramethyl-2-imidazolin-2-yl) phenyl ester (4) as a biradical analogue of 2, it is shown that the intramolecular ferromagnetic interaction has been found to be unaffected by the chemical modification for anchoring the monoradical moiety.     

pH and molar ratio dependent formation of monomeric,dimeric and tetrameric cobalt malate complexes

The reactions of cobalt(II) chloride with racemic malic acid (H₃mal = C₄H₆O₅) result in the isolation of monomeric, dimeric and tetrameric cobalt malato complexes: (NH₄)₂[Co(R-Hmal)(S-Hmal)] · 2H₂O (1), [Co₂(R-Hmal)(S-Hmal)(H₂O)₄]_n · 2nH₂O (2), K₄[Co₄(OH)₂(R-mal)₂(S-mal)₂(H₂O)₄] · 10H₂O (3) and trans-[Co(R-H₂mal)(S-H₂mal)(H₂O)₂] · 2H₂O (4). The formations of the malato complexes are dependent on the pH value, the molar ratio of the solutions, the reaction temperature and the counterions. In the water-soluble compound 1, the Co^II ion is octahedrally coordinated by two tridentate malates via their α-hydroxy, α-carboxy and β-carboxy groups. The malate ligands in 2 coordinate with the cobalt ion via their α-hydroxy and α-carboxy groups, while the β-carboxy group acts as a bridging ligand for the other two cobalt ions, forming a novel dimeric unit [Co₂(R-Hmal)(S-Hmal)(H₂O)₄], which further connects into a layered structure through links from the oxygen atoms of the β-carboxy groups. Complex 3 is a tetranuclear mixed-valence species. Both of the Co^II ions exist in trans-[Co(R-mal)(S-mal)(H₂O)₂] units, which are linked by a Co^III₂(OH)₂ unit with bridging α-alkoxy and β-carboxy groups. Compound 4 is the main product of reaction between cobalt chloride and excess malate under weakly acidic conditions.     

Prediction of COVID-19 manipulation by selective ACE inhibitory compounds of Potentilla reptant root: In silico study and ADMET profile

In the novel SARS-CoV-2 (COVID-19) as a global emergency event, the main reason of the cardiac injury from COVID-19 is angiotensin-converting enzyme 2 (ACE2) targeting in SARS-CoV-2 infection. The inhibition of ACE2 induces an increase in the angiotensin II (Ang II) and the angiotensin II receptor type 1 (AT1R) leading to impaired cardiac function or cardiac inflammatory responses. The ethyl acetate fraction of Potentilla reptans L. root can rescue heart dysfunction, oxidative stress, cardiac arrhythmias and apoptosis. Therefore, isolated components of P. reptans evaluated to identify natural anti-SARS-CoV-2 agents via molecular docking.In silico molecular docking study were carried out using the Auto Dock software on the isolated compounds of Potentilla reptans root. The protein targets of selective ACE and others obtained from Protein Data Bank (PDB). The best binding pose between amino acid residues involved in active site of the targets and compounds was discovered via molecular docking. Furthermore, ADMET properties of the compounds were evaluated.The triterpenoids of P. reptans showed more ACE inhibitory potential than catechin in both domains. They were selective on the nACE domain, especially compound 5. Also, the compound 5 & 6 had the highest binding affinity toward active site of nACE, cACE, AT1R, ACE2, and TNF-α receptors. Meanwhile, compound 3 showed more activity to inhibit TXA2. Drug likeness and ADMET analysis showed that the compounds passed the criteria of drug likeness and Lipinski rules. The current study depicted that P. reptans root showed cardioprotective effect in COVID-19 infection and manipulation of angiotensin II-induced side effects.     

Antifungal diastereomeric furanones from Mutisia friesiana: structural determination and conformational analysis

Two diastereomeric furanones, (4S,5S)-5-(4′-methyl-3′-pentenyl)-4-hydroxy-5-methyldihydrofuran-2-one 1 and (4S,5R)-5-(4′-methyl-3′-pentenyl)-4-hydroxy-5-methyldihydrofuran-2-one 2 were isolated for the first time from the shrub Mutisia friesiana. The relative stereochemistries of 1 and 2 were ascertained from NOESY NMR data and confirmed by a combination of molecular modeling (molecular mechanics and ab initio molecular orbital calculations) and NMR data. Comparison between experimental and calculated ¹H–¹H vicinal coupling constants revealed that both furanones exist in an equilibrium of two stable conformers of the five-membered ring. Application of Mosher's method suggests that both diastereomeric furanones have the same (S)-configuration at C-(4) and are epimers at C-(5). Furanones 1 and 2 showed antifungal activity against the pathogenic fungus Cladosporium cucumerinum.     

Electropolymerization of cobalt porphyrins and corroles for the oxygen evolution reaction

Developing large-scale electrocatalysts using molecular complexes for the oxygen evolution reaction (OER) is of great importance. Herein, four cobalt porphyrins and corroles are deposited on electrode substrates using a simple and fast electropolymerization method. Our results showed that Co-1-P@CC, formed by electropolymerizing Co tetrakis(p-N-pyrrolylphenyl)porphyrin (Co-1-P) on carbon cloth (CC), is the most active OER catalyst in the examined Co porphyrins and corroles in alkaline aqueous solutions by displaying an onset overpotential of 380 mV. Long-term electrolysis tests confirmed the stability of these electropolymerized films by functioning as OER electrocatalysts.     

Synthesis, crystal structures and electrochemical properties of CoIII complexes with hexadentate ligand containing thioether-amidopyridyl donor set

Two new cobalt(III) complexes of the hexadentate ligand [1,4-bis[o-(pyridine-2-carboxamidophenyl)]-1,4-dithiobutane] (H₂bpctb) with N₄S₂ donor set atoms have been synthesized. A reaction of Co(CH₃COO)₂·4H₂O with (H₂bpctb) leads to the formation of [Co^III(bpctb)]PF₆ (1) having a CoN₂(pyridine)N′₂(amide)S₂(thioether) coordination by symmetric bpctb^2? ligand. A similar reaction under slightly different conditions, however, gives [Co^III(L ^a )(L ^b )] (2), resulting from a C–S bond cleavage reaction triggered by an acetate ion as a base, having CoN₂(pyridine)N′₂(amide)S(thioether)S′(thiolate) coordination. These two Co(III) complexes have been characterized by elemental analyses and spectroscopic methods, and the crystal and molecular structures of [Co^III(bpctb)]PF₆ (1) in the form of the solvate (1·MeOH·H₂O) and of [Co^III(L ^a )(L ^b )] (2) have been determined by X-ray crystallography. The Co atoms of both complexes exhibit distorted octahedral geometry. The electrochemical investigation of [Co(bpctb)]PF₆·MeOH·H₂O (1·MeOH·H₂O) and [Co^III(L ^a )(L ^b )] (2) by cyclic voltammetry reveals a reversible Co^III–Co^II redox process at E _1/2 = ?0.32 V (ΔE _p = 80 mV); for 1, and E _1/2 = ?0. 87 V (ΔE _p = 70 mV) for 2.     

Practical methods for the preparation of spiro[benzo[c]thiophene-1(3H),4′-piperidine]-(2S)-oxide by resolution and asymmetric sulfoxidation

We report simple and efficient methods for the preparation of enantiomerically pure spiro[benzo[c]thiophene-1(3H),4′-piperidine]-(2S)-oxide (S)-1, a key intermediate for the synthesis of tachykinin receptor antagonist, by resolution and asymmetric sulfoxidation. Racemic (RS)-1 can be resolved with (S)-(+)-mandelic acid in acetonitrile to give (S)-1 of >99% ee. We also describe the asymmetric sulfoxidation of sulfide 5 in excellent enantiomeric excess and high chemical yield by the use of the Davis reagent.     

Crystal structure,thermal behavior,and microbiological activity of a thiosemicarbazide-type ligand and its cobalt complexes

The synthesis of a potentially bioactive mixed-valence Co^III/Co^II complex with 2-acetylpyridine S-methylisothiosemicarbazone (HL) ligand is described. The crystal and molecular structure of the formed [Co^IIIL₂][Co^IICl₃ py]·Me₂CO (I) compound (py stands for pyridine) is determined by single-crystal X-ray crystallography. It’s thermal decomposition along with the decomposition of the ligand and six structurally related complexes with formulas [CoL₂]NO₃·MeOH (1), [CoL₂]Br·MeOH (2), [CoL₂]HSO₄·MeOH (3), [CoL₂]₂[Co^II(NCS)₄] (4), [Co(HL)(L)]I₂·2MeOH (5), and [Co(HL)(L)][Co^IICl₄]·MeOH (6) was determined by simultaneous TG/DSC measurements. The decomposition pattern is evaluated using TG/DTA-MS data. The results were related to the solvent/moisture content and the decomposition mechanism of the compounds. The antimicrobial activity of the ligand and of all the complexes was tested in vitro for selected gram-negative and gram-positive bacteria and fungi. The activity of the ligand against all tested bacteria is comparable with those obtained for standard antibiotics, while it is less active against fungi. Surprisingly, the activity of the complexes is very low. The low antimicrobial activity of the complexes may be in connection with their high thermodynamic and kinetic inertness in solution. The results are also supported by the relatively high thermal stability of the complexes.     

2-Oxo-3,4-dihydropyrimido[4,5-d] pyrimidines as new reversible inhibitors of EGFR C797S (Cys797 to Ser797) mutant

Extensive structure-activity relationships (SARs) study of JND3229 was conducted to yield a series of new reversible 2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidine privileged scaffold as EGFR^C797S inhibitors. One of the most potent compound 6i potently suppressed EGFR^{L858R/T790M/C797S} kinase with an IC₅₀ value of 3.1 nmol/L, and inhibited the proliferation of BaF3 cells harboring EGFR^{L858R/T790M/C797S} and EGFR^{19D/T790M/C797S} mutants with IC₅₀ values of 290 nmol/L and 316 nmol/L, respectively. Further, 6i dose-dependently induced suppression of the phosphorylation of EGFR^{L858R/T790M/C797S} and EGFR^{19D/T790M/C797S} in BaF3 cells. Compound 6i may serve as a promising lead compound for further drug discovery overcoming the acquired resistance of non-small cell lung cancer (NSCLC) patients.     

A structure and an absolute configuration of (+)-alternamin, a new coumarin from Murraya alternans having antidote activity against snake venom

(+)-Alternamin (1), a new dihydrofuranocoumarin, was isolated from the aerial parts of Murraya alternans (Kurz) Swingle. The analysis 2-D NMR correlation of (+)-1 led to either of linear dihydrofuranocoumarin (2A, 2C) or angular one (2B). An IR and a vibrational circular dichroism (VCD) studies were conducted to distinguish the structure and to assign the absolute configuration. By comparison of the observed spectra with the calculated spectra for (S)-2A, (S)-2B, and (R)-2C, the molecular structure of (+)-1 was determined to be (S)-(+)-5,8-dimethoxymarmesin. The compound exhibited antidote activity against snake venom from Trimeresurus flavoviridis, affording experimental support for the pharmacological use of M. alternans.     

碳纳米纤维负载Co_3S_4复合材料的合成及其在染料敏化太阳电池对电极的应用

采用水热法合成四硫化三钴(Co_3S_4)催化材料,并利用球磨和喷涂技术将其制备成对电极,结合新型无碘电解液Co~(2+)/Co~(3+)用于染料敏化太阳电池(dye-sensitized solar cells,简称DSCs)来研究其光电性能。测试结果显示,基于Co_3S_4对电极,DSCs的能量转化效率(power conversion efficiency,简称PCE)只有6.06%,远远低于Pt对电极(8.05%)。为了提高Co_3S_4的催化能力,采用静电纺丝技术制备碳纳米纤维(electrospun carbon nanofibers,简称ECs),结合水热法制备出不同负载量的碳纳米纤维负载四硫化三钴(Co_3S_4/ECs)复合催化材料用于对电极,结果表明,Co_3S_4/ECs的PCE最高可达(8.22±0.08)%,优于Pt对电极。