Triazole-tethered ferrocene-quinoline conjugates: solid-state structure analysis, electrochemistry and theoretical calculations

Djaković, Senka; Maračić, Silvija; Lapić, Jasmina; Kovalski, Eduard; Hildebrandt, Alexander; Lang, Heinrich; Vrček, Valerije; Raić‐Malić, Silvana

doi:10.1007/s11224-021-01801-2

Cited by 4 publications

(4 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Comparing these values leads to the conclusion that the first oxidation occurs at the Fc moiety directly bonded to the 1,2,3-triazole core. Such an assignment is consistent with data obtained for other ferrocenyl-1,2,3-triazole systems 83 − 85 and supported by DFT calculations (see the SI ). In the following electrochemical process, the respective FcC≡C unit is oxidized.…”

Section: Resultssupporting

confidence: 90%

Electronic Coupling in 1,2,3-Triazole Bridged Ferrocenes and Its Impact on Reactive Oxygen Species Generation and Deleterious Activity in Cancer Cells

et al. 2022

Self Cite

View full text Add to dashboard Cite

Mixed-valence (MV) binuclear ferrocenyl compounds have long been studied as models for testing theories of electron transfer and in attempts to design molecular-scale electronic devices ( e.g ., molecular wires). In contrary to that, far less attention has been paid to MV binuclear ferrocenes as anticancer agents. Herein, we discuss the synthesis of six 1,2,3-triazole ferrocenyl compounds for combined (spectro)electrochemical, electron paramagnetic resonance (EPR), computational, and anticancer activity studies. Our synthetic approach was based on the copper-catalyzed 1,3-dipolar azide–alkyne cycloaddition reaction and enabled us to obtain in one step compounds bearing either one, two, or three ferrocenyl entities linked to the common 1,2,3-triazole core. Thus, two series of complexes were obtained, which pertain to derivatives of 3′-azido-3′-deoxythymidine (AZT) and 3-azidopropionylferrocene, respectively. Based on the experimental and theoretical data, the two mono-oxidized species corresponding to binuclear AZT and trinuclear 3-azidopropionylferrocene complexes have been categorized as class II mixed-valence according to the classification proposed by Robin and Day. Of importance is the observation that these two compounds are more active against human A549 and H1975 non-small-cell lung cancer cells than their congeners, which do not show MV characteristics. Moreover, the anticancer activity of MV species competes or surpasses, dependent on the cell line, the activity of reference anticancer drugs such as cisplatin, tamoxifen, and 5-fluorouracil. The most active from the entire series of compounds was the binuclear thymidine derivative with the lowest IC 50 value of 5 ± 2 μM against lung H1975 cancer cells. The major mechanism of antiproliferative activity for the investigated MV compounds is based on reactive oxygen species generation in cancer cells. This hypothesis was substantiated by EPR spin-trapping experiments and the observation of decreased anticancer activity in the presence of N -acetyl cysteine (NAC) free-radical scavenger.

show abstract

Section: Resultssupporting

confidence: 90%

Electronic Coupling in 1,2,3-Triazole Bridged Ferrocenes and Its Impact on Reactive Oxygen Species Generation and Deleterious Activity in Cancer Cells

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, the conformation of the methylene groups in 5a is synclinal , as the same torsion angle amounts −57.4(2) o . The bond distances in 5a and 6d are consistent with the corresponding distances in closely related structures 39,54,55 …”

Section: Resultssupporting

confidence: 81%

“…The bond distances in 5a and 6d are consistent with the corresponding distances in closely related structures. 39,54,55 Only one type of intermolecular hydrogen bond, C-HÁÁÁN, connects the molecules of 5a (Table 3). All other interactions link the molecules of 5a with dichloromethane molecules present in this structure.…”

Section: X-ray Crystal Structure Studiesmentioning

confidence: 99%

“…[36][37][38] Although substantial attention has been directed toward reducing environmental impact, utilization of mechanochemistry in the synthesis of pharmaceuticals and drug-like compounds has not yet been adequately investigated. 31 The promising antiproliferative activity of ferrocenes conjugated with N-heterocycle in I ÀIII via 1,2,3-triazole 12,14,39 prompted us to further study the anticancer potential of a series of 1,1 0 -disubstituted ferrocene derivatives bearing quinoline (5a-5d and 6a-6d) or quinolone (7a, 7b, 8a, and 8b) moiety (Figure 1). In contrast to the well-developed milling procedures of click reactions, 38,[40][41][42] this is the first attempt of LAG mechanochemical synthesis of ferrocenes containing 1,2,3-triazole moiety, which may guide further research on LAG mechanosynthesis in medicinal organometallic chemistry.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mechanochemical synthesis and antiproliferative activity of novel ferrocene quinoline/quinolone hybrids

Maračić

Jakopec

Piškor

et al. 2023

Applied Organom Chemis

Self Cite

View full text Add to dashboard Cite

The synthesis of novel 1,1′‐disubstituted ferrocene conjugates appended with N‐1 and O‐4 alkylated quinolone and quinoline was reported. The target compounds were synthesized employing a liquid‐assisted grinding (LAG) mechanochemical method in copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) to obtain ferrocene−quinoline/quinolone hybrids (5a–5d, 6a–6d, 7a, 7b, 8a, and 8b) in higher yields and shorter reaction time compared to a conventional method, thus proving superiority of mechanochemistry versus conventional synthesis. Bis‐quinoline and bis‐quinolone ferrocene derivatives were evaluated for their antiproliferative effects on five selected tumor and two non‐tumor cell lines. Bis‐6‐methylquinolone–ferrocene conjugate 8b showed the best antiproliferative effect on T‐cell lymphoma (HuT78) cells (IC50 = 14.8 μM) and no cytotoxicity on both non‐tumor MDCK1 and BJ cells. Results obtained after mitochondrial membrane potential (∆Ψm) measurement using flow cytometry showed that compound 8b caused accumulation of HuT78 cells in subG0/G1 phase, disturbance of mitochondrial membrane potential, and apoptosis. The structure of the quinolone and ferrocene hybrid 8b can be further optimized to obtain candidates with better inhibitory effects on HuT78 cells.

show abstract

New Ferrocene-Based Metalloligand with Two Triazole Carboxamide Pendant Arms and Its Iron(II) Complex: Synthesis, Crystal Structure, 57Fe Mössbauer Spectroscopy, Magnetic Properties and Theoretical Calculations

et al. 2022

View full text Add to dashboard Cite

The new ferrocene-based metalloligand bis (N-4-[3,5-di-(2-pyridyl)-1,2,4-triazoyl])ferrocene carboxamide (L) was prepared through derivatization of 1,1′-ferrocenedicarboxylic acid with 4-amino-3,5-di(pyridyl)-4H-1,2,4-triazole. The composition and purity of L in the solid state was determined with elemental analysis, FT-IR spectroscopy, and its crystal structure with single-crystal X-ray analysis, which revealed that the substituted cyclopentadienyl rings adopt the antiperiplanar conformation and the crystal structure of L is stabilized by O–H···N and N–H···O hydrogen bonds. The molecular properties of L in solution were investigated with NMR and UV-VIS spectroscopies, and cyclic voltammetry disclosed irreversible redox behavior providing one oxidation peak at E1/2 = 1.133 V vs. SHE. Furthermore, the polymeric FeII complex {Fe(L)(C(CN)3)2}n (1) was prepared and characterized with elemental analysis, FT-IR spectroscopy, 57Fe Mössbauer spectroscopy, and magnetic measurements. The last two methods confirmed that a mixture of low- and high-spin species is present in 1; however, the spin crossover properties were absent. The presented study was also supported by theoretical calculations at the DFT/TD-DFT level of theory using TPSS and TPSSh functionals.

show abstract

Triazole-tethered ferrocene-quinoline conjugates: solid-state structure analysis, electrochemistry and theoretical calculations

Cited by 4 publications

References 78 publications

Electronic Coupling in 1,2,3-Triazole Bridged Ferrocenes and Its Impact on Reactive Oxygen Species Generation and Deleterious Activity in Cancer Cells

Electronic Coupling in 1,2,3-Triazole Bridged Ferrocenes and Its Impact on Reactive Oxygen Species Generation and Deleterious Activity in Cancer Cells

Mechanochemical synthesis and antiproliferative activity of novel ferrocene quinoline/quinolone hybrids

New Ferrocene-Based Metalloligand with Two Triazole Carboxamide Pendant Arms and Its Iron(II) Complex: Synthesis, Crystal Structure, 57Fe Mössbauer Spectroscopy, Magnetic Properties and Theoretical Calculations

Contact Info

Product

Resources

About