Synthesis of Cobalt Bis(Dicarbollide)—Curcumin Conjugates for Potential Use in Boron Neutron Capture Therapy

A series of novel cobalt bis(dicarbollide)—curcumin conjugates were synthesized. Two conjugates were obtained through the nucleophilic ring-opening reaction of the 1,4-dioxane and tetrahydropyran derivatives of cobalt bis(dicarbollide) with the OH group of curcumin, and using two equiv. of the oxonium derivatives, two other conjugates containing two cobalt bis(dicarbollide) units per molecule were obtained. In contrast to curcumin, the conjugates obtained were found to be non-cytotoxic against both tumor and normal cell lines. The analysis of the intracellular accumulation of the conjugates by flow cytometry showed that all cobalt bis(dicarbollide)—curcumin conjugates entered HCT116 colorectal carcinoma cells in a time-dependent manner. New non-cytotoxic conjugates contain a large amount of boron atoms in the biomolecule and can potentially be used for further biological research into boron neutron capture therapy (BNCT).     

Synthesis and Structure of Nido-Carboranyl Azide and Its “Click” Reactions

Novel zwitter-ionic nido-carboranyl azide 9-N₃(CH₂)₃Me₂N-nido-7,8-C₂B₉H₁₁ was prepared by the reaction of 9-Cl(CH₂)₃Me₂N-nido-7,8-C₂B₉H₁₁ with NaN₃. The solid-state molecular structure of nido-carboranyl azide was determined by single-crystal X-ray diffraction. 9-N₃(CH₂)₃Me₂N-nido-7,8-C₂B₉H₁₁ was used for the copper(I)-catalyzed azide-alkyne cycloaddition with phenylacetylene, alkynyl-3β-cholesterol and cobalt/iron bis(dicarbollide) terminal alkynes to form the target 1,2,3-triazoles. The nido-carborane-cholesterol conjugate 9-3β-Chol-O(CH₂)C-CH-N₃(CH₂)₃Me₂N-nido-7,8-C₂B₉H₁₁ with charge-compensated group in a linker can be used as a precursor for preparation of liposomes for Boron Neutron Capture Therapy (BNCT). A series of novel zwitter-ionic boron-enriched cluster compounds bearing a 1,2,3-triazol-metallacarborane-carborane conjugated system was synthesized. Prepared conjugates contain a large amount of boron atom in the biomolecule and potentially can be used for BNCT.     

Boron-Containing Lipids and Liposomes: New Conjugates of Cholesterol with Polyhedral Boron Hydrides

A series of boron-containing lipids were prepared by reactions of cyclic oxonium derivatives of polyhedron boranes and metallacarboranes (closo-dodecaborate anion, cobalt and iron bis(dicarbollides)) with amine and carboxylic acids which are derived from cholesterol. Stable liposomal formulations, on the basis of synthesized boron-containing lipids, hydrogenated soybean l -α-phosphatidylcholine and (HSPC) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) as excipients, were prepared and then characterized by dynamic light scattering (DLS) that revealed the formation of particles to be smaller than 200 nm in diameter. The resulting liposomal formulations showed moderate to excellent loading and entrapment efficiency, thus justifying the design of the compounds to fit in the lipid bilayer and ensuring ease of in vivo use for future application. The liposomal formulations based on cobalt and iron bis(dicarbollide)-based lipids were found to be nontoxic against both human breast normal epithelial cells MCF-10A and human breast cancer cells MCF-7.     

New Azido Coumarins as Potential Agents for Fluorescent Labeling and Their “Click” Chemistry Reactions for the Conjugation with closo-Dodecaborate Anion

Novel fluorescent 7-methoxy- and 7-(diethylamino)-coumarins modified with azido-group on the side chain have been synthesized. Their photophysical properties and single crystals structure characteristics have been studied. In order to demonstrate the possibilities of fluorescent labeling, obtained coumarins have been tested with closo-dodecaborate derivative bearing terminal alkynyl group. Cu^I catalyzed Huisgen 1,3-dipolar cycloaddition reaction has led to fluorescent conjugates formation. The absorption–emission spectra of the formed conjugates have been presented. The antiproliferative activity and uptake of compounds against several human cell lines were evaluated.     

Synthesis of Boronated Amidines by Addition of Amines to Nitrilium Derivative of Cobalt Bis(Dicarbollide)

A series of novel cobalt bis(dicarbollide) based amidines were synthesized by the nucleophilic addition of primary and secondary amines to highly activated B-N⁺≡C–R triple bond of the propionitrilium derivative [8-EtC≡N-3,3′-Co(1,2-C₂B₉H₁₀)(1′,2′-C₂B₉H₁₁)]. The reactions with primary amines result in the formation of mixtures of E and Z isomers of amidines, whereas the reactions with secondary amines lead selectively to the E-isomers. The crystal molecular structures of E-[8-EtC(NMe₂)=HN-3,3′-Co(1,2-C₂B₉H₁₀)(1′,2′-C₂B₉H₁₁)], E-[8-EtC(NEt₂)=HN-3,3′-Co(1,2- C₂B₉H₁₀)(1′,2′-C₂B₉H₁₁)] and E-[8-EtC(NC₅H₁₀)=HN-3,3′-Co(1,2-C₂B₉H₁₀)(1′,2′-C₂B₉H₁₁)] were determined by single crystal X-ray diffraction.     

Synthesis of Zwitter-Ionic Conjugate of Nido-Carborane with Cholesterol

9-HC≡CCH₂Me₂N-nido-7,8-C₂B₉H₁₁, a previously described carboranyl terminal alkyne, was used for the copper(I)-catalyzed azide-alkyne cycloaddition with azido-3β-cholesterol to form a novel zwitter-ionic conjugate of nido-carborane with cholesterol, bearing a 1,2,3-triazol fragment. The conjugate of nido-carborane with cholesterol, containing a charge-compensated group in the linker, can be used as a precursor for the preparation of liposomes for BNCT (Boron Neutron Capture Therapy). The solid-state molecular structure of a nido-carborane derivative with the 9-Me₂N(CH₂)₂Me₂N-nido-7,8-C₂B₉H₁₁ terminal dimethylamino group was determined by single-crystal X-ray diffraction.     

Tethered Blatter Radical for Molecular Grafting: Synthesis of 6-Hydroxyhexyloxy,Hydroxymethyl, and Bis(hydroxymethyl) Derivatives and Their Functionalization

Synthetic access to 7-CF₃-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl radicals containing 4-(6-hydroxyhexyloxy)phenyl, 4-hydroxymethylphenyl or 3,5-bis(hydroxymethyl)phenyl groups at the C(3) position and their conversion to tosylates and phosphates are described. The tosylates were used to obtain disulfides and an azide with good yields. The Blatter radical containing the azido group underwent a copper(I)-catalyzed azide–alkyne cycloaddition with phenylacetylene under mild conditions, giving the [1,2,3]triazole product in 84% yield. This indicates the suitability of the azido derivative for grafting Blatter radical onto other molecular objects via the CuAAC “click” reaction. The presented derivatives are promising for accessing surfaces and macromolecules spin-labeled with the Blatter radical.     

Synthesis and Structure of the Bis- and Tris-Polyhedral Hybrid Carboranoclathrochelates with Functionalizing Biorelevant Substituents—The Derivatives of Propargylamine Iron(II) Clathrochelates with Terminal Triple C≡C Bond(s)

A synthetic strategy for obtaining structurally flexible hybrid iron(II) carboranoclatrochelates functionalized with biorelevant groups, based on a combination of a 1,3-dipolar cycloaddition reaction with nucleophilic substitution of an appropriate chloroclathrochelate precursor, was developed. In its first stage, a stepwise substitution of the dichloroclathrochelate precursor with amine N-nucleophiles of different natures in various solvents was performed. One of its two chlorine atoms with morpholine or diethylamine in dichloromethane gave reactive monohalogenoclathrochelate complexes functionalized with abiorelevant substituents. Further nucleophilic substitution of their remaining chlorine atoms with propargylamine in DMF led to morpholine- and diethylamine-functionalized monopropargylamine cage complexes, the molecules of which contain the single terminal C≡C bond. Their “click” 1,3-cycloaddition reactions in toluene with ortho-carborane-(1)-methylazide catalyzed by copper(II) acetate gave spacer-containing di- and tritopic iron(II) carboranoclatrochelates formed by a covalent linking between their different polyhedral(cage) fragments. The obtained complexes were characterized using elemental analysis, MALDI-TOF mass, UV-Vis, ¹H, ¹H{¹¹B}, ¹¹B, ¹¹B{¹H}, ¹⁹F{¹H} and ¹³C{¹H}-NMR spectra, and by a single crystal synchrotron X-ray diffraction experiment for the diethylamine-functionalized iron(II) carboranoclathrochelate. Its encapsulated iron(II) ion is situated almost in the center of the FeN₆-coordination polyhedron possessing a geometry intermediate between a trigonal prism and a trigonal antiprism with a distortion angle φ of approximately 28°. Conformation of this hybrid molecule is strongly affected by its intramolecular dihydrogen bonding: a flexibility of the carborane-terminated ribbed substituent allowed the formation of numerous C–H…H–B intramolecular interactions. The H(C) atom of this carborane core also forms the intermolecular C–H…F–B interaction with an adjacent carboranoclathrochelate molecule. The N–H…N intermolecular interaction between the diethylamine group of one hybrid molecule and the heterocyclic five-membered 1H-[1,2,3]-triazolyl fragment of the second molecule of this type caused formation of H-bonded carboranoclathrochelate dimers in the X-rayed crystal.     

桥连双(酮亚胺)和双(二酮亚胺)及其铝配合物的合成与催化活性

通过桥连双β-二酮类化合物与取代苯胺反应, 合成了5个新的桥连双(β-单酮亚胺)化合物(1~5)和2个新的桥连双(β-二酮亚胺)化合物(6,7), 它们与三甲基铝反应, 得到了相应的3个双(β-酮亚胺基)二铝配合物(8~10)和2个双(β-二酮亚胺基)二铝配合物(11,12). 采用核磁共振、 红外光谱和质谱等对这些化合物进行了表征, 通过X射线单晶衍射分析证实了铝配合物的结构, 并考察了这些铝配合物在ε-己内酯开环聚合反应中的催化活性.     

An anthracene based fluorescent probe for the selective and sensitive detection of Chromium (III) ions in an aqueous medium and its practical application

An anthracene based fluorescent probe, integrated with thiophene moiety, exhibited selective and sensitive detection of chromium (III) ions over other metal ions. Its synthesis was achieved by simple mixing of two commercially available compounds, 2-aminoanthracene, and 2-thiophenecarboxaldehyde, in onestep without the needed complex purification process. The probe molecule ( ANT-Th ) offered exceptional features such as “turn-on” fluorescence response, low detection limit (0.4 μM), and fast response time (<1 min) via C=N bond hydrolysis. Also, a simple test paper system was developed for the rapid detection of chromium (III) ions with the naked eye.     

The Influence of HCl Concentration on the Rate of the Hydrolysis–Condensation Reaction of Phenyltrichlorosilane and the Yield of (Tetrahydroxy)(Tetraphenyl)Cyclotetrasiloxanes,Synthesis of All Its Geometrical Isomers and Thermal Self-Condensation of Them under “Pseudo”-Equilibrium Conditions

The rate of hydrolysis–condensation reaction of phenyltrichlorosilane in water-acetone solutions and the product yields were shown to significantly depend on the concentration of HCl (C_HCl) in the solutions. The main product of the reaction was all-cis-(tetrahydroxy)(tetraphenyl)cyclotetrasiloxane. This was different from the earlier published results of analogous reactions of m-tolylSiCl₃, m-ClPhSiCl₃, and α-naphtylSiCl, in which some products of other types were formed. For example, trans-1,1,3,3-tetrahydroxy-1,3-di-α-naphtyldisiloxane was obtained in the case of α-naphtylSiCl₃. All-cis-(tetrahydroxy)(tetraphenyl)cyclotetrasiloxane was treated in acetone with HCl to give the other three geometric isomers (cis-cis-trans-, cis-trans-, and all-trans-). The thermal self-condensation of these four isomers under “pseudo”-equilibrium conditions (under atmospheric pressure) was investigated in different solvents, in quartz or molybdenum glass flasks. The compositions of the products were monitored by APCI-MS and ²⁹Si NMR spectroscopy. It was shown that all-cis- and cis-cis-trans-isomers in toluene or anisole mostly gave the cage-like Ph-T_8,10,12,14 and uncompleted cage-like Ph-T_10,12OSi(HO)Ph compounds. In contrast to these two isomers, the cis-trans–isomer in toluene mainly formed dimers with the loss of one or two molecules of water. However, in acetonitrile, significant amounts of Ph-T_10,12 and Ph-T_10,12OSi(HO)Ph species were formed along with the dimers. All-trans-isomer did not enter into the reaction at all.     

N,N'-二(2-羟苄基)取代咪唑烷的合成、表征及抑菌活性

利用生物活性叠加原理,将"邻羟苯基"和"咪唑烷"分子片断有机结合,以水杨醛和乙二胺为起始原料,经缩合、NaBH4还原制得N,N'-二邻羟苄基乙二胺(2),进而与芳醛类化合物缩合关环,合成了8种N,N'-二(2-羟苄基)取代咪唑烷类化合物(3a～3h). 化合物的结构经1H NMR、IR、MS和元素分析等测试技术进行了表征. 结果表明,水杨醛与乙二胺的缩合反应,可专一性地生成对称双缩席夫碱化合物(1);芳醛上的取代基对缩合关环反应有显著影响,邻、对位吸电基可使芳醛的羰基活化,有利于缩合关环反应的进行,邻、对位供电基可使芳醛的羰基钝化,不利于缩合关环反应进行. 抑菌测试结果表明,质量分数为0.1%时,N,N'-二(2-羟苄基)取代咪唑烷化合物对不同菌株的抑菌活性具有明显的特异性,对白色念珠菌、大肠杆菌的抑菌率达100%.     

Synthesis of 3-Aryl-3-(Furan-2-yl)Propanoic Acid Derivatives,and Study of Their Antimicrobial Activity

Reactions of 3-(furan-2-yl)propenoic acids and their esters with arenes in Brønsted superacid TfOH affords products of hydroarylation of the carbon–carbon double bond, 3-aryl-3-(furan-2-yl)propenoic acid derivatives. According to NMR and DFT studies, the corresponding O,C-diprotonated forms of the starting furan acids and esters should be reactive electrophilic species in these transformations. Starting compounds and their hydroarylation products, at a concentration of 64 µg/mL, demonstrate good antimicrobial activity against yeast-like fungi Candida albicans. Apart from that, these compounds suppress Escherichia coli and Staphylococcus aureus.     

Synthesis and Photophysical Properties of α-(N-Biphenyl)-Substituted 2,2′-Bipyridine-Based Push–Pull Fluorophores

A series of new α-(N-biphenyl)-substituted 2,2′-bipyridines were obtained through the combination of the ipso-nucleophilic aromatic substitution of the C5-cyano group, aza-Diels–Alder and Suzuki cross-coupling reactions, starting from 5-cyano-1,2,4-triazines. For the obtained compounds, photophysical and fluorosolvatochromic properties were studied. Fluorophores 3l and 3b demonstrated unexpected AIEE activity, while 3a and 3h showed promising nitroexplosive detection abilities.     

Phytochemical and Biological Activity Studies on Nasturtium officinale (Watercress) Microshoot Cultures Grown in RITA® Temporary Immersion Systems

The main compounds in both extracts were gluconasturtiin, 4-methoxyglucobrassicin and rutoside, the amounts of which were, respectively, determined as 182.93, 58.86 and 23.24 mg/100 g dry weight (DW) in biomass extracts and 640.94, 23.47 and 7.20 mg/100 g DW in plant herb extracts. The antioxidant potential of all the studied extracts evaluated using CUPRAC (CUPric Reducing Antioxidant Activity), FRAP (Ferric Reducing Ability of Plasma), and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays was comparable. The anti-inflammatory activity of the extracts was tested based on the inhibition of 15-lipoxygenase, cyclooxygenase-1, cyclooxygenase-2 (COX-2), and phospholipase A₂. The results demonstrate significantly higher inhibition of COX-2 for in vitro cultured biomass compared with the herb extracts (75.4 and 41.1%, respectively). Moreover, all the studied extracts showed almost similar antibacterial and antifungal potential. Based on these findings, and due to the fact that the growth of in vitro microshoots is independent of environmental conditions and unaffected by environmental pollution, we propose that biomass that can be rapidly grown in RITA^® bioreactors can serve as an alternative source of bioactive compounds with valuable biological properties.     

Regioselective One-Pot Synthesis,Biological Activity and Molecular Docking Studies of Novel Conjugates N-(p-Aryltriazolyl)-1,5-benzodiazepin-2-ones as Potent Antibacterial and Antifungal Agents

Novel 1,2,3-triazolo-linked-1,5-benzodiazepinones were designed and synthesized via a Cu(I)-catalyzed 1,3-dipolar alkyne-azide coupling reaction (CuAAC). The chemical structures of these compounds were confirmed by ¹H NMR, ¹³C NMR, HMBC, HRMS, and elemental analysis. The compounds were screened for their in vitro antibacterial and antifungal activities. Several compounds exhibited good to moderate activities compared to those of established standard drugs. Furthermore, the binding interactions of these active analogs were confirmed through molecular docking.     

Synthesis,Characterization, and Reaction Studies of Pd(II) Tripeptide Complexes

The aqueous synthesis of Pd(II) complexes with alkylated tripeptides led to the hydrolysis of the peptides at low pH values and mixtures of complexed peptides were formed. A non-aqueous synthetic route allowed the formation and isolation of single products and their characterization. Pd(II) complexes with α-Asp(OR)AlaGly(OR), β-Asp(OR)AlaGly(OR), and TrpAlaGly(OR) (R = H or alkyl) as tri and tetradentate chelates were characterized. The tridentate coordination mode was accompanied by a fourth monodentate ligand that was shown to participate in both ligand exchange reactions and a direct removal to form the tetradentate coordination mode. The tetradentate coordination revealed a rare a hemi labile carbonyl goup coordination mode to Pd(II). Reactivity with small molecules such as ethylene, acids, formate, and episulfide was investigated. Under acidic conditions and in the presence of ethylene; acetaldehyde was formed. The Pd(II) is a soft Lewis acid and thiophilic and the complexes abstract sulfur from episulfide at apparent modest catalytic rates. The complexes adopt a square planar geometry according to a spectroscopic analysis and DFT calculations that were employed to evaluate the most energetically favorable coordination geometry and compared with the observed infrared and NMR data.     

一种新型2，6-吡啶二甲酸镓(Ⅲ)配合物的合成、结构及抑菌活性研究(英)

A novel coordination polymer [NaGa(dipic)₂(H₂O)₂]_n was synthesized by the reaction of gallium(Ⅲ) trichloride with Na-salt of 2,6-pyridinedicarboxylic acid and its crystal structure was determined by X-ray diffraction method. The crystal belongs to monoclinic, space group Cc; the unit cell parameters are a=1.502 9(3), b=1.228 1(3) and c=0.872 38(17) nm, β=92.85(3)°, and Z=4, V=1.608 2(6) nm³, F(000)=920. Infrared, electronic absorption, ¹H NMR spectra, as well as the thermal behavior are reported. The antibacterial activity of the gallium(Ⅲ) complex has been studied against Escherichia coli, Bacillus subtilis and Staphylococcus aureus in order to check its potential for chemotherapy agent. The activity is notable and higher than that of the H₂L. CCDC: 240619.     

Catalytic Performance of Cobalt(II) Polyethylene Catalysts with Sterically Hindered Dibenzopyranyl Substituents Studied by Experimental and MLR Methods

Given the great importance of cobalt catalysts supported by benchmark bis(imino)pyridine in the (oligo)polymerization, a series of dibenzopyran-incorporated symmetrical 2,6-bis(imino) pyridyl cobalt complexes (Co1–Co5) are designed and prepared using a one-pot template approach. The structures of the resulting complexes are well characterized by a number of techniques. After activation with either methylaluminoxane (MAO) or modified MAO (MMAO), the complexes Co1–Co4 are highly active for ethylene polymerization with a maximum activity of up to 7.36 × 10⁶ g (PE) mol⁻¹ (Co) h⁻¹ and produced highly linear polyethylene with narrow molecular weight distributions, while Co5 is completely inactive under the standard conditions. Particularly, complex Co3 affords polyethylene with high molecular weights of 85.02 and 79.85 kg mol⁻¹ in the presence of MAO and MMAO, respectively. The ¹H and ¹³C NMR spectroscopy revealed the existence of vinyl end groups in the resulting polyethylene, highlighting the predominant involvement of the β-H elimination reaction in the chain-termination process. To investigate the mechanism underlying the variation of catalytic activities as a function of substituents, multiple linear regression (MLR) analysis was performed, showing the key role of open cone angle (θ) and effective net charge (Q) on catalytic activity.