Synthesis and Investigations of the Antitumor Effects of First-Row Transition Metal(II) Complexes Supported by Two Fluorinated and Non-Fluorinated ß-Diketonates.

The 3d transition metal (Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II)) complexes, supported by anions of sterically demanding ß-diketones, 1,3-dimesitylpropane-1,3-dione (HLMes) and 1,3-bis(3,5-bis(trifluoromethyl)phenyl)-3-hydroxyprop-2-en-1-one (HLCF3), were synthesized and evaluated for their antitumor activity. To assess the biological effects of substituents on phenyl moieties, we also synthesized and investigated the analogous metal(II) complexes of the anion of the less bulky 1,3-diphenylpropane-1,3-dione (HLPh) ligand. The compounds [Cu(LCF3)2], [Cu(LMes)2] and ([Zn(LMes)2]) were characterized by X-ray crystallography. The [Cu(LCF3)2] crystallizes with an apical molecule of solvent (THF) and features a rare square pyramidal geometry at the Cu(II) center. The copper(II) and zinc(II) complexes of diketonate ligands, derived from the deprotonated 1,3-dimesitylpropane-1,3-dione (HLMes), adopt a square planar or a tetrahedral geometry at the metal, respectively. We evaluated the antitumor properties of the newly synthesized (Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II)) complexes against a series of human tumor cell lines derived from different solid tumors. Except for iron derivatives, cellular studies revealed noteworthy antitumor properties, even towards cancer cells endowed with poor sensitivity to the reference drug cisplatin.

Correction: When SF5 outplays CF3: effects of pentafluorosulfanyl decorated scorpionates on copper.

[This corrects the article DOI: 10.1039/D1SC04846E.].

Understanding Copper(I)-Ethylene Bonding Using Cu K-Edge X-ray Absorption Spectroscopy.

Copper plays many important roles in ethylene chemistry, thus generating significant interest in understanding the structures, bonding, and properties of copper(I)-ethylene complexes. In this work, the ethylene binding characteristics of a series of isolable Cu(I)-ethylene compounds supported by a systematic set of fluorinated and nonfluorinated bis- and tris(pyrazolyl)borate and the related bis(pyrazolyl)methane ligands have been investigated. Through a combination of X-ray absorption spectroscopy and quantum chemical calculations, we characterize their geometric and electronic structures and the role that fluorinated ligands play in lowering the electron density at Cu sites. Such ligands increase the ethylene-to-Cu σ-donor interaction and, correspondingly, decrease the Cu-to-ethylene π back-bonding. This latter interaction leads to a partial vacancy in the Cu 3d level, which manifests experimentally as a low-energy feature in the Cu K pre-edge, allowing for its direct observation and comparison within a series of Cu(I) compounds. The pre-edge feature is reproduced by TD-DFT calculations, and its energy position and total intensity are used to quantitatively probe Cu-ethylene bonding. The variations in the Cu electronic structure influence the stability and overall ethylene bonding strength of these compounds, ultimately showing how substituents on the supporting ligands have a notable effect on their physical and chemical properties.

Synthesis and cytotoxicity studies of Cu(I) and Ag(I) complexes based on sterically hindered ß-diketonates with different degrees of fluorination.

Design, synthesis, and in vitro antitumor properties of Cu(I) and Ag(I) phosphane complexes supported by the anions of sterically hindered ß-diketone ligands, 1,3-dimesitylpropane-1,3-dione (HLMes) and 1,3-bis(3,5-bis(trifluoromethyl)phenyl)-3-hydroxyprop-2-en-1-one (HLCF3) featuring trifluoromethyl or methyl groups on the phenyl moieties have been reported. In order to compare the biological effects of substituents on the phenyl moieties, the analogous copper(I) and silver(I) complexes of the anion of the parent 1,3-diphenylpropane-1,3-dione (HLPh) ligand were also synthesized and included in the study. In the syntheses of the Cu(I) and Ag(I) complexes, the phosphane coligands triphenylphosphine (PPh3) and 1,3,5-triaza-7-phosphaadamantane (PTA) were used to stabilize silver and copper in the +1 oxidation state, preventing the metal ion reduction to Ag(0) or oxidation to Cu(II), respectively. X-ray crystal structures of HLCF3 and the metal adducts [Cu(LCF3)(PPh3)2] and [Ag(LPh)(PPh3)2] are also presented. The antitumor properties of both classes of metal complexes were evaluated against a series of human tumor cell lines derived from different solid tumors, by means of both 2D and 3D cell viability studies. They display noteworthy antitumor properties and are more potent than cisplatin in inhibiting cancer cell growth.

Copper(I), Silver(I), and Gold(I) Ethylene Complexes of Fluorinated and Boron-Methylated Bis- and Tris(pyridyl)borate Chelators.

Bis- and tris-pyridyl borate ligands containing pyridyl donor arms, a methylated boron cap, and a fluorine-lined coordination pocket have been prepared and utilized in coinage metal chemistry. The tris(pyridyl)borate ligand has been synthesized using a convenient boron source, [NBu4][MeBF3]. These N-based ligands permitted the isolation of group 11 metal-ethylene complexes [MeB(6-(CF3)Py)3]M(C2H4) and [Me2B(6-(CF3)Py)2]M(C2H4) (M = Cu, Ag, Au). The gold complexes display the largest coordination-induced upfield shifts of the ethylene 13C resonance relative to that of the free ethylene in their NMR spectra, while the silver complexes show the smallest shift. Solid-state structures of five of these metal-ethylene complexes as well as the related free ligands were established by X-ray crystallography. Surprisingly, all three [MeB(6-(CF3)Py)3]M(C2H4) adopt the rare κ2 coordination mode rather than the typical κ3 coordination mode of facial capping tridentate ligands. Computational analyses indicate that κ2 coordination mode is favored over the κ3-mode in these coinage metal-ethylene complexes and point to the effects CF3-substituents have on κ2/κ3-energy difference. The M-C and M-N bond distances of [MeB(6-(CF3)Py)3]M(C2H4) follow the trend expected based on covalent radii of M(I) ions. The calculated ethylene-M interaction energy of κ2-[MeB(6-(CF3)Py)3]M(C2H4) indicated that the gold(I) forms the strongest interaction with ethylene. A comparison to the related poly(pyrazolyl)borates is also presented.

Remarkably Selective Propylene-Propane Separation Using a Copper Scorpionate.

Propylene is a crucial building block to produce many industrial-scale chemicals including polypropylene. The separation of propylene from propane to reach the high-purity levels needed for downstream applications is a difficult task due to the close similarities in their physical properties. The olefin/paraffin separation including that involving propylene mainly relies on highly energy-intensive distillation processes and accounts for nearly 0.3% of the global energy consumption. The utility of a copper complex supported by a fluorinated bis(pyrazolyl)borate is demonstrated to accomplish the separation of propylene from propane repeatedly, under mild conditions with high selectivity. Complete characterization of a rare, copper(I) propylene complex is also reported including the molecular structure.

Isolable acetylene complexes of copper and silver.

Copper and silver play important roles in acetylene transformations but isolable molecules with acetylene bonded to Cu(i) and Ag(i) ions are scarce. This report describes the stabilization of π-acetylene complexes of such metal ions supported by fluorinated and non-fluorinated, pyrazole-based chelators. These Cu(i) and Ag(i) complexes were formed readily in solutions under an atmosphere of excess acetylene and the appropriate ligand supported metal precursor, and could be isolated as crystalline solids, enabling complete characterization using multiple tools including X-ray crystallography. Molecules that display κ2-or κ3-ligand coordination modes and trigonal planar or tetrahedral metal centers have been observed. Different trends in coordination shifts of the acetylenic carbon resonance were revealed by 13C NMR spectroscopy for the Cu(i) and Ag(i) complexes. The reduction in acetylene [italic small nu, Greek, macron] C[triple bond, length as m-dash]C due to metal ion coordination is relatively large for copper adducts. Computational tools were also used to quantitatively understand in detail the bonding situation in these species. It is found that the interaction between the transition metal fragment and the acetylene ligand is significantly stronger in the copper complexes, which is consistent with the experimental findings. The C[triple bond, length as m-dash]C distance of these copper and silver acetylene complexes resulting from routine X-ray models suffers due to incomplete deconvolution of thermal smearing and anisotropy of the electron density in acetylene, and is shorter than expected. A method to estimate the C[triple bond, length as m-dash]C distance of these metal complexes based on their experimental [italic small nu, Greek, macron] C[triple bond, length as m-dash]C is also presented.

Bonding situation in isolable silver(I) carbonyl complexes of the Scorpionates.

The bonding situation of Ag(I)CO complexes having a Scorpionate ligand directly attached to the transition metal has been analyzed in detail by means of relativistic density functional theory calculations. To this end, different experimentally characterized complexes together with other representative species have been considered to rationalize the observed shift of the corresponding ν(CO) stretching frequencies and the influence of the substituents in the Scorpionate ligand. With the help of the energy decomposition analysis method combined with the natural orbital for chemical valence it is found that the main contribution to the bonding comes from the electrostatic attractions between the LAg(I) and CO fragments. Despite that, the LAg â†’ CO π-backdonation is also significant in these species as well as in related LCu(I)CO complexes.

Iron pentacarbonyl ligands on silver scorpionates.

Fluorinated tris(pyrazolyl)borate supporting ligands enable the stabilization of silver(I) bonded to a neutral, organometallic Fe(CO)5 ligand. The Ag-Fe interaction in these molecules is mainly electrostatic in nature, but σ-donor and backbonding contributions between the two metal fragments also play notable roles, which can be modulated by the scorpionate substituents.

Binding Interactions in Copper, Silver and Gold π-Complexes.

The copper(I), silver(I), and gold(I) metals bind π-ligands by σ-bonding and π-back bonding interactions. These interactions were investigated using bidentate ancillary ligands with electron donating and withdrawing substituents. The π-ligands span from ethylene to larger terminal and internal alkenes and alkynes. Results of X-ray crystallography, NMR, and IR spectroscopy and gas phase experiments show that the binding energies increase in the order Ag

Synthesis, molecular docking studies, and in vitro antimicrobial evaluation of piperazine and triazolo-pyrazine derivatives.

For this work, two series of new piperazine derivatives (3a-o) and triazolo-pyrazine derivatives (3p-t) were synthesized in a single-step reaction. All twenty adducts were obtained in good to high yields and fully characterized by 1H NMR, 13C NMR, IR, and mass spectrometry techniques. To further confirm the chemical identity of the adducts, a crystal of N-{[(4-chlorophenyl)-3-(trifluoromethyl)]-5,6-dihydro-[1,2,4]triazolo[4,3-a]}pyrazine-7(8H)-carboxamide (3t) was prepared and analyzed using X-ray crystallography. In vitro screening of the antimicrobial activity of all compounds (3a-t) was evaluated against five bacterial and two fungal strains. This study disclosed that N-{[(3-chlorophenyl)]-4-(dibenzo[b,f][1,4]thiazepin-11-yl)}piperazine-1-carboxamide (3o) was the superior antimicrobial with good growth inhibition against A. baumannii. Furthermore, the results from the performed molecular docking studies were promising, since the observed data could be used to develop more potent antimicrobials.

When SF5 outplays CF3: effects of pentafluorosulfanyl decorated scorpionates on copper.

Polyfluorinated, electron-withdrawing, and sterically demanding supporting ligands are of significant value in chemistry. Here we report the assembly and use of a bis(pyrazolyl)borate, [Ph2B(3-(SF5)Pz)2]- that combines all such features, and involves underutilized pentafluorosulfanyl substituents. The ethylene and carbonyl chemistry of copper(i) supported by [Ph2B(3-(SF5)Pz)2]-, a comparison to the trifluoromethylated counterparts involving [Ph2B(3-(CF3)Pz)2]-, as well as copper catalyzed cyclopropanation of styrene with ethyl diazoacetate and CF3CHN2 are presented. The results from cyclopropanation show that SF5 groups dramatically improved the yields and stereoselectivity compared to the CF3.

A Molecular Compound for Highly Selective Purification of Ethylene.

Purification of C2 H4 from an C2 H4 /C2 H6 mixture is one of the most challenging separation processes, which is achieved mainly through energy-intensive, cryogenic distillation in industry. Sustainable, non-distillation methods are highly desired as alternatives. We discovered that the fluorinated bis(pyrazolyl)borate ligand supported copper(I) complex {[(CF3 )2 Bp]Cu}3 has features very desirable in an olefin-paraffin separation material. It binds ethylene exclusively over ethane generating [(CF3 )2 Bp]Cu(C2 H4 ). This molecular compound exhibits extremely high and record ideal adsorbed solution theory (IAST) C2 H4 /C2 H6 gas separation selectivity, affording high purity (>99.5 %) ethylene that can be readily desorbed from separation columns. In-situ PXRD provides a "live" picture of the reversible conversion between [(CF3 )2 Bp]Cu(C2 H4 ) and the ethylene-free sorbent in the solid-state, driven by the presence or removal of C2 H4 . Molecular structures of trinuclear {[(CF3 )2 Bp]Cu}3 and mononuclear [(CF3 )2 Bp]Cu(C2 H4 ) are also presented.

Gold(I) ethylene complexes supported by electron-rich scorpionates.

Ethylene complexes of gold(i) have been stabilized by electron-rich, κ2-bound tris(pyrazolyl)borate ligands. Large up-field shifts of olefinic carbon NMR resonances and relatively long C[double bond, length as m-dash]C distances of gold bound ethylene are indicative of significant Au(i) → ethylene π-backbonding relative to the analog supported by a weakly donating ligand, consistent with the computational data.

Terminal and Internal Alkyne Complexes and Azide-Alkyne Cycloaddition Chemistry of Copper(I) Supported by a Fluorinated Bis(pyrazolyl)borate.

Copper plays an important role in alkyne coordination chemistry and transformations. This report describes the isolation and full characterization of a thermally stable, copper(I) acetylene complex using a highly fluorinated bis(pyrazolyl)borate ligand support. Details of the related copper(I) complex of HC≡CSiMe3 are also reported. They are three-coordinate copper complexes featuring η2-bound alkynes. Raman data show significant red-shifts in C≡C stretch of [H2B(3,5-(CF3)2Pz)2]Cu(HC≡CH) and [H2B(3,5-(CF3)2Pz)2]Cu(HC≡CSiMe3) relative to those of the corresponding alkynes. Computational analysis using DFT indicates that the Cu(I) alkyne interaction in these molecules is primarily of the electrostatic character. The π-backbonding is the larger component of the orbital contribution to the interaction. The dinuclear complexes such as Cu2(µ-[3,5-(CF3)2Pz])2(HC≡CH)2 display similar Cu-alkyne bonding features. The mononuclear [H2B(3,5-(CF3)2Pz)2]Cu(NCMe) complex catalyzes [3 + 2] cycloadditions between tolyl azide and a variety of alkynes including acetylene. It is comparatively less effective than the related trinuclear copper catalyst {µ-[3,5-(CF3)2Pz]Cu}3 involving bridging pyrazolates.

Isolable Copper(I) η2-Cyclopropene Complexes.

Treatment of bis(pyrazolyl)borate ligand supported [(CF3)2Bp]Cu(NCMe) with 1,2,3-trisubstituted cyclopropenes produced thermally stable copper(I) η2-cyclopropene complexes amenable to detailed solution and solid-state analysis. The [(CF3)2Bp]Cu(NCMe) also catalyzed [2 + 1]-cycloaddition chemistry of terminal and internal alkynes with ethyl diazoacetate affording cyclopropenes, including those used as ligands in this work. The tris(pyrazolyl)borate [(CF3)2Tp]Cu(NCMe) is a competent catalyst for this process as well. The treatment of [(CF3)2Tp]Cu with ethyl 2,3-diethylcycloprop-2-enecarboxylate substrate gave an O-bonded rather than a η2-cyclopropene copper complex.

New Urea Derivatives as Potential Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies.

A series of new urea derivatives, containing aryl moieties as potential antimicrobial agents, were designed, synthesized, and characterized by 1H NMR, 13C NMR, FT-IR, and LCMS spectral techniques. All newly synthesized compounds were screened in vitro against five bacterial strains (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus) and two fungal strains (Candida albicans and Cryptococcus neoformans). Variable levels of interaction were observed for these urea derivatives. However, and of major importance, many of these molecules exhibited promising growth inhibition against Acinetobacter baumannii. In particular, to our delight, the adamantyl urea adduct 3l demonstrated outstanding growth inhibition (94.5%) towards Acinetobacter baumannii. In light of this discovery, molecular docking studies were performed in order to elucidate the binding interaction mechanisms of the most active compounds, as reported herein.

Acetylene and terminal alkyne complexes of copper(i) supported by fluorinated pyrazolates: syntheses, structures, and transformations.

Trinuclear {µ-[3,5-(CF3)2Pz]Cu}3 reacts with acetylene to produce the 2 : 1 copper(i) acetylene complex, Cu4(µ-[3,5-(CF3)2Pz])4(µ-HC[triple bond, length as m-dash]CH)2. Related Cu4(µ-[4-Br-3,5-(CF3)2Pz])4(µ-HC[triple bond, length as m-dash]CH)2 and Cu4(µ-[4-Cl-3,5-(CF3)2Pz])4(µ-HC[triple bond, length as m-dash]CH)2 have also been isolated using the corresponding copper(i) pyrazolate and acetylene. The 1 : 1 adducts Cu2(µ-[3,5-(CF3)2Pz])2(HC[triple bond, length as m-dash]CH)2 and Cu2(µ-[4-Br-3,5-(CF3)2Pz])2(HC[triple bond, length as m-dash]CH)2 are significantly less stable to the acetylene loss and can be observed in solution at low temperatures under excess acetylene. The X-ray crystal structures of 2 : 1 and 1 : 1 complexes, Cu4(µ-[3,5-(CF3)2Pz])4(µ-HC[triple bond, length as m-dash]CH)2 and Cu2(µ-[4-Br-3,5-(CF3)2Pz])2(HC[triple bond, length as m-dash]CH)2 are reported. Raman data show a reduction in [small nu, Greek, macron]C[triple bond, length as m-dash]C stretching frequency by about ∼340 and ∼163 cm-1 in the 2 : 1 and 1 : 1 Cu(i)/acetylene complexes, respectively, from that of the free acetylene. Copper(i) pyrazolate complexes of the terminal alkynes, phenylacetylene, 1,8-nonadiyne, and 1,7-octadiyne are also reported. They form adducts involving one copper atom on each alkyne moiety. The {µ-[3,5-(CF3)2Pz]Cu}3 is also a very versatile and competent catalyst for alkyne transformations as evident from its ability to catalyze the alkyne C(sp)-H bond carboxylation chemistry with CO2, azide-alkyne cycloadditions leading to 1,2,3-triazoles including the use of acetylene itself as a substrate, and thiol addition to phenylacetylene affording vinyl sulfides.

Design, synthesis, and molecular docking study of new piperazine derivative as potential antimicrobial agents.

Herein, we describe the successful design and synthesis of seventeen new 1,4-diazinanes, compounds commonly known as piperazines. This group of piperazine derivatives (3a-q) were fully characterized by 1H NMR, 13C NMR, FT-IR, and LCMS spectral techniques. The molecular structure of piperazine derivative (3h) was further established by single crystal X-ray diffraction analysis. All reported compounds were evaluated for their antibacterial and antifungal potential against five bacterial (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) and two fungal strains (Candida albicans and Cryptococcus neoformans). The complete bacterial screening results are provided. As documented, piperazine derivative 3e performed the best against these bacteria. Additionally, data obtained during molecular docking studies are very encouraging with respect to potential utilization of these compounds to help overcome microbe resistance to pharmaceutical drugs, as explicitly noted in this manuscript.