Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Strategy to Conjugate Bioactive Fragments to Cytotoxic Diiron Bis(cyclopentadienyl) Complexes.

ABSTRACT: A series of bioactive molecules were synthesized from the condensation of aspirin or chlorambucil with terminal alkynes bearing alcohol or amine substituents. Insertion of the resulting alkynes into the iron-carbyne bond of readily accessible diiron bis(cyclopentadienyl) μ-aminocarbyne complexes, [1a,b]CF₃SO₃, afforded novel diiron complexes with a bridging vinyliminium ligand, [2-10]CF₃SO₃, functionalized with a bioactive moiety. All compounds were characterized by elemental analysis and IR and multinuclear NMR spectroscopy and in three cases by single-crystal X-ray diffraction. Moreover, the D₂O solubility, stability in D₂O and cell culture media, and octanol-water partition coefficients of diiron complexes were determined spectroscopically. The cytotoxicity of the complexes was assessed in the tumorigenic A2780 and A2780cisR and the nontumorigenic HEK 293T cell lines. Some complexes exhibit high potency and the ability to overcome resistance in A2780cisR cells (aspirin complexes) or high selectivity relative to HEK 293T cells (chlorambucil complexes). Further studies indicate that the complexes significantly trigger intracellular ROS production, irrespective of the nature of the bioactive fragment. DNA alkylation and protein binding studies were also undertaken.

SUBMITTER: Schoch S

PROVIDER: S-EPMC8397425 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Triptycene-based Bis(benzimidazole) Carboxylate-Bridged Biomimetic Diiron(II) Complexes.

Project description:A triptycene-based bis(benzimidazole) ester ligand, L3, was designed to enhance the electron donating ability of the heterocyclic nitrogen atoms relative to those of the first generation bis(benzoxazole) analogs, L1 and L2. A convergent synthesis of L3 was designed and executed. Three-component titration experiments using UV-visible spectroscopy revealed that the desired diiron(II) complex could be obtained with a 1:2:1 ratio of L3:Fe(OTf)2(MeCN)2:external carboxylate reactants. X-ray crystallographic studies of two diiron complexes derived in this manner from L3 revealed their formulas to be [Fe2L3(?-OH)(?-O2CR)(OTf)2], where R = 2,6-bis(p-tolyl)benzoate (7) or triphenylacetate (8). The structures are similar to that of a diiron complex derived from L1, [Fe2L1(?-OH)(?-O2CArTol)(OTf)2] (9) with a notable difference being that, in 7 and 8, the geometry at iron more closely resembles square-pyramidal than trigonal-bipyramidal. Mössbauer spectroscopic analyses of 7 and 8 indicate the presence of high-spin diiron(II) cores. These results demonstrate the importance of substituting benzimidazole for benzoxazole for assembling biomimetic diiron complexes with syn disposition of two N-donor ligands, as found in O2-activating carboxylate-bridged diiron centers in biology.

| S-EPMC3625018 | biostudies-literature

A ?-Carbon elimination strategy for convenient <i>in situ</i> access to cyclopentadienyl metal complexes.

Project description:The electronic and steric properties of tailored cyclopentadienyl (Cp) ligands are powerful handles to modulate the catalytic properties of their metal complexes. This requires the individual preparation, purification and storage of each ligand/metal combination. Alternative, ideally in situ, complexation protocols would be of high utility. We disclose a new approach to access Cp metal complexes. Common metal precursors rapidly react with cyclopentadienyl carbinols via ?-carbon eliminations to directly give the Cp-metal complexes. An advantage of this is the direct and flexible use of storable pre-ligands. No auxiliary base is required and the Cp complexes can be prepared in situ in the reaction vessel for subsequent catalytic transformations.

| S-EPMC5635420 | biostudies-literature

Donor-Stabilized Monocarba-Bridged Bis(cyclopentadienyl)alanes.

Project description:Five monocarba-bridged bis(cyclopentadienyl)aluminum halide NHC and thione complexes and one monocarba-bridged bis(cyclopentadienyl)phosphanylalane NHC complex are reported. The former were synthesized by transmetalation of a C[1]magnesocenophane with the corresponding aluminum(III) chloride and aluminum(III) bromide donor adducts. The phosphanylalane complex was obtained by a subsequent functionalization of the corresponding bromoalane with lithium diphenylphosphide. All complexes were characterized in solution by multinuclear NMR spectroscopy and in the solid state by single crystal X-ray diffraction. Bonding energies of the NHC and thione ligands to the aluminum centres were estimated by DFT calculations.

| S-EPMC7607447 | biostudies-literature

Easily Available, Amphiphilic Diiron Cyclopentadienyl Complexes Exhibit in Vitro Anticancer Activity in 2D and 3D Human Cancer Cells through Redox Modulation Triggered by CO Release.

Project description:A straightforward two-step procedure via single CO removal allows the conversion of commercial [Fe2 Cp2 (CO)4 ] into a range of amphiphilic and robust ionic complexes based on a hybrid aminocarbyne/iminium ligand, [Fe2 Cp2 (CO)3 {CN(R)(R')}]X (R, R'=alkyl or aryl; X=CF3 SO3 or BF4 ), on up to multigram scales. Their physicochemical properties can be modulated by an appropriate choice of N-substituents and counteranion. Tested against a panel of human cancer cell lines, the complexes were shown to possess promising antiproliferative activity and to circumvent multidrug resistance. Interestingly, most derivatives also retained a significant cytotoxic activity against human cancer 3D cell cultures. Among them, the complex with R=4-C6 H4 OMe and R'=Me emerged as the best performer of the series, being on average about six times more active against cancer cells than a noncancerous cell line, and displayed IC50 values comparable to those of cisplatin in 3D cell cultures. Mechanistic studies revealed the ability of the complexes to release carbon monoxide and to act as oxidative stress inducers in cancer cells.

| S-EPMC8362065 | biostudies-literature

Synthesis of Diiron(I) Dithiolato Carbonyl Complexes.

Project description:Virtually all organosulfur compounds react with Fe(0) carbonyls to give the title complexes. These reactions are reviewed in light of major advances over the past few decades, spurred by interest in Fe2(?-SR)2(CO)x centers at the active sites of the [FeFe]-hydrogenase enzymes. The most useful synthetic route to Fe2(?-SR)2(CO)6 involves the reaction of thiols with Fe2(CO)9 and Fe3(CO)12. Such reactions can proceed via mono-, di-, and triiron intermediates. The reactivity of Fe(0) carbonyls toward thiols is highly chemoselective, and the resulting dithiolato complexes are fairly rugged. Thus, many complexes tolerate further synthetic elaboration directed at the organic substituents. A second major route involves alkylation of Fe2(?-S2)(CO)6, Fe2(?-SH)2(CO)6, and Li2Fe2(?-S)2(CO)6. This approach is especially useful for azadithiolates Fe2[(?-SCH2)2NR](CO)6. Elaborate complexes arise via addition of the FeSH group to electrophilic alkenes, alkynes, and carbonyls. Although the first example of Fe2(?-SR)2(CO)6 was prepared from ferrous reagents, ferrous compounds are infrequently used, although the Fe(II)(SR)2 + Fe(0) condensation reaction is promising. Almost invariably low-yielding, the reaction of Fe3(CO)12, S8, and a variety of unsaturated substrates results in C-H activation, affording otherwise inaccessible derivatives. Thiones and related C?S-containing reagents are highly reactive toward Fe(0), often giving complexes derived from substituted methanedithiolates and C-H activation.

| S-EPMC4933964 | biostudies-literature

The ansa-zirconocene [bis(eta(5)-cyclopentadienyl)phenylphosphine]dichloridozirconium(IV).

Project description:In the title compound, [Zr(C(16)H(13)P)Cl(2)], the geometry at the metal atom is distorted tetrahedral; the Cl-Zr-Cl angle is 101.490 (16) degrees and the cyclopentadienyl (Cp) centroids subtend an angle of 122.63 (3) degrees at the Zr atom. The P atom lies 0.474 (3) and 0.496 (3) A out of the planes of the Cp rings. The C-P-C angle of 91.42 (7) degrees reflects the pincer effect of the two Cp rings. Three C-H...Cl, one C-H...P, one C-H...pi and one Cl...P interaction link the molecules to form thick layers parallel to the bc plane.

| S-EPMC2855579 | biostudies-literature

Electron-Rich, Diiron Bis(monothiolato) Carbonyls: C-S Bond Homolysis in a Mixed Valence Diiron Dithiolate.

Project description:The synthesis and redox properties are presented for the electron-rich bis(monothiolate)s Fe2(SR)2(CO)2(dppv)2 for R = Me ([1]0), Ph ([2]0), CH2Ph ([3]0). Whereas related derivatives adopt C2-symmetric Fe2(CO)2P4 cores, [1]0-[3]0 have Cs symmetry resulting from the unsymmetrical steric properties of the axial vs equatorial R groups. Complexes [1]0-[3]0 undergo 1e- oxidation upon treatment with ferrocenium salts to give the mixed valence cations [Fe2(SR)2(CO)2(dppv)2]+. As established crystallographically, [3]+ adopts a rotated structure, characteristic of related mixed valence diiron complexes. Unlike [1]+ and [2]+ and many other [Fe2(SR)2L6]+ derivatives, [3]+ undergoes C-S bond homolysis, affording the diferrous sulfido-thiolate [Fe2(SCH2Ph)(S)(CO)2(dppv)2]+ ([4]+). According to X-ray crystallography, the first coordination spheres of [3]+ and [4]+ are similar, but the Fe-sulfido bonds are short in [4]+. The conversion of [3]+ to [4]+ follows first-order kinetics, with k = 2.3 × 10-6 s-1 (30 °C). When the conversion is conducted in THF, the organic products are toluene and dibenzyl. In the presence of TEMPO, the conversion of [3]+ to [4]+ is accelerated about 10×, the main organic product being TEMPO-CH2Ph. DFT calculations predict that the homolysis of a C-S bond is exergonic for [Fe2(SCH2Ph)2(CO)2(PR3)4]+ but endergonic for the neutral complex as well as less substituted cations. The unsaturated character of [4]+ is indicated by its double carbonylation to give [Fe2(SCH2Ph)(S)(CO)4(dppv)2]+ ([5]+), which adopts a bioctahedral structure.

| S-EPMC5927630 | biostudies-literature

Design and Anticancer Properties of New Water-Soluble Ruthenium-Cyclopentadienyl Complexes.

Project description:Ruthenium complexes are emerging as one of the most promising classes of complexes for cancer therapy. However, their limited aqueous solubility may be the major limitation to their potential clinical application. In view and to contribute to the progress of this field, eight new water-soluble Ru(II) organometallic complexes of general formula [RuCp(mTPPMS)n(L)] [CF3SO3], where mTPPMS = diphenylphosphane-benzene-3-sulfonate, for n = 2, L is an imidazole-based ligand (imidazole, 1-benzylimidazole, 1-butylimidazole, (1-(3-aminopropyl)imidazole), and (1-(4-methoxyphenyl)imidazole)), and for n = 1, L is a bidentate heteroaromatic ligand (2-benzoylpyridine, (di(2-pyridyl)ketone), and (1,2-(2-pyridyl)benzo-[b]thiophene)) were synthesized and characterized. The new complexes were fully characterized by NMR, FT-IR, UV-vis., ESI-HRMS, and cyclic voltammetry, which confirmed all the proposed molecular structures. The antiproliferative potential of the new Ru(II) complexes was evaluated on MDAMB231 breast adenocarcinoma, A2780 ovarian carcinoma, and HT29 colorectal adenocarcinoma cell lines, showing micromolar (MDAMB231 and HT29) and submicromolar (A2780) IC50 values. The interaction of complex 6 with human serum albumin (HSA) and fatty-acid-free human serum albumin (HSAfaf) was evaluated by fluorescence spectroscopy techniques, and the results revealed that the ruthenium complex strongly quenches the intrinsic fluorescence of albumin in both cases.

| S-EPMC9321894 | biostudies-literature

Anticancer Diiron Vinyliminium Complexes: A Structure-Activity Relationship Study.

Project description:A series of 16 novel diiron complexes of general formula [Fe2Cp2(CO)(μ-CO){μ-η1:η3-C(R')C(R″)CN(R)(Y)}]CF3SO3 (2-7), bearing different substituents on the bridging vinyliminium ligand, was synthesized in 69-95% yields from the reactions of diiron μ-aminocarbyne precursors with various alkynes. The products were characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy; moreover the X-ray structures of 2c (R = Y = CH2Ph, R' = R″ = Me) and 3a (R = CH2CH=CH2, Y = R' = Me, R″ = H) were ascertained by single-crystal X-ray diffraction studies. NMR and UV-Vis methods were used to assess the D2O solubility, the stability in aqueous solution at 37 °C and the octanol-water partition coefficients of the complexes. A screening study evidenced a potent cytotoxicity of 2-7 against the A2780 cancer cell line, with a remarkable selectivity compared to the nontumoral Balb/3T3 cell line; complex 4c (R = Cy, Y = R' = R″ = Me) revealed as the most performant of the series. The antiproliferative activity of a selection of complexes was also assessed on the cisplatin-resistant A2780cisR cancer cell line, and these complexes were capable of inducing a significant ROS production. Moreover, ESI-MS experiments indicated the absence of interaction of selected complexes with cytochrome c and the potentiality to inhibit the thioredoxin reductase enzyme (TrxR).

| S-EPMC8398472 | biostudies-literature

Ruthenium(II)-Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs.

Project description:Colorectal cancer (CRC) is one of the most common malignancies and one of the leading causes of cancer-related death worldwide, urging the need for new and more efficient therapeutic approaches. Ruthenium complexes have emerged as attractive alternatives to traditional platinum-based compounds in the treatment of CRC. This work aims to evaluate anti-CRC properties, as well as to identify the mechanisms of action of ruthenium complexes with the general formula [Ru(η5-C5H4R)(PPh3)(4,4'-R'-2,2'-bipyridine)][CF3SO3], where R = CH3, CHO or CH2OH and R' = H, CH3, CH2OH, or dibiotin ester. The complexes (Ru 1-7) displayed high bioactivity, as shown by low IC50 concentrations against CRC cells, namely, RKO and SW480. Four of the most promising ruthenium complexes (Ru 2, 5-7) were phenotypically characterized and were shown to inhibit cell viability by decreasing cell proliferation, inducing cell cycle arrest, and increasing apoptosis. These findings were in accordance with the inhibition of MEK/ERK and PI3K/AKT signaling pathways. Ruthenium complexes also led to a decrease in cellular clonogenic ability and cell migration, which was associated with the disruption of F-actin cytoskeleton integrity. Here, we demonstrated that ruthenium complexes, especially Ru7, have a high anticancer effect against CRC cells and are promising drugs to be used as a new therapeutical strategy for CRC treatment.

| S-EPMC9228117 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data