The Influence of the Auxiliary Ligand in Monofunctional Pt(II) Anticancer Complexes on the DNA Backbone.

Monofunctional platinum complexes offer a promising alternative to cisplatin in cancer chemotherapy, showing a unique mechanism of action. Their ability to induce minor helix distortions effectively inhibits DNA transcription. In our study, we synthesized and characterized three monofunctional Pt(II) complexes with the general formula [Pt(en)(L)Cl]NO3, where en = ethylenediamine, and L = pyridine (py), 2-methylpyridine (2-mepy), and 2-phenylpyridine (2-phpy). The hydrolysis rates of [Pt(en)(py)Cl]NO3 (1) and [Pt(en)(2-mepy)Cl]NO3 (2) decrease with the bulkiness of the auxiliary ligand with k(1) = 2.28 ± 0.15 × 10-4 s-1 and k(2) = 8.69 ± 0.98 × 10-5 s-1 at 298 K. The complex [Pt(en)(2-phpy)Cl]Cl (3) demonstrated distinct behavior. Upon hydrolysis, an equilibrium (Keq = 0.385 mM) between the complexes [Pt(en)(2-phpy)Cl]+ and [Pt(en)(2-phpy-H+)]+ was observed with no evidence (NMR or HR-ESI-MS) for the presence of the aquated complex [Pt(en)(2-phpy)(H2O)]2+. Despite the kinetic similarities between phenanthriplatin and (2), complexes (1) and (2) exhibit minimal activity against A549 lung cancer cell line (IC50 > 100 µΜ), whereas complex (3) exhibits notable cytotoxicity (IC50 = 41.11 ± 2.1 µΜ). In examining the DNA binding of (1) and (2) to the DNA model guanosine (guo), we validated their binding through guoN7, which led to an increased population of the C3'-endo sugar conformation, as expected. However, we observed that the rapid transition 2E (C2'-endo) ↔ 3E (C3'-endo), in the case of [Pt(en)(py)(guo)](NO3)2 ([1-guo]), slows down in the case of [Pt(en)(2-mepy)(guo)](NO3)2 ([2-guo]), resulting in separate signals for the two conformers in the 1H NMR spectra. This phenomenon arises from the steric hindrance between the methyl group of pyridine and the sugar moiety of guanosine. Notably, this hindrance is absent in [2-(9-MeG)] (9-MeG = 9-methylguanine), probably due to the absence of a bulky sugar unit in 9-MeG. In the case of (3), where the bulkiness of the substitution on the pyridine is further increased by a phenyl group, we observed a notable proximity between 9-MeGH8 and the phenyl ring of 2-phpy. Considering that only (3) exhibited good cytotoxicity against the A549 cancer cell line, it is suggested that auxiliary ligands, L, with an extended aromatic system and proper orientation in complexes of the type cis-[Pt(en)(L)Cl]NO3, may enhance the cytotoxic activity of such complexes.

NMR Analysis of Extra Virgin Olive Oil of the Epirus Region of Greece with Emphasis on Selected Phenolic Compounds.

Extra virgin olive oil (EVOO) is recognized for its numerous health benefits, attributed to its rich phenolic components. NMR has emerged as a prevalent technique for precisely identifying these compounds. Among Mediterranean countries, Greece stands as the third-largest producer of olives, with the Epirus region notably advancing in olive cultivation, contributing significantly to the dynamic growth of the region. In this study, an NMR method was employed based on the acquisition of a 1H NMR spectrum along with multiple resonant suppression in order to increase the sensitivity. Using the above method, 198 samples of extra virgin olive oil, primarily sourced from the Epirus region, were analyzed, and both the qualitative and quantitative aspects of the phenolic compounds were obtained. In addition, we examined the effects of various factors such as variety, harvest month, and region origin on the phenolic compounds' concentration. The results revealed an average total phenolic content of 246 mg/kg, closely approaching the EU health claim limit of 250 mg/kg. Approximately 15% of the samples were confidently characterized as high-phenolic olive oil. The highest concentrations were observed in the Thesprotia samples, with several Lianolia varieties exceeding the total phenolic content of 400 mg/kg. Statistical tests demonstrated a significant influence of the olive variety and the month of fruit harvest on phenolic component concentration, followed by the region of origin. A very strong correlation was noted between the total phenolics content and the levels of oleocanthal and oleacein, with a correlation coefficient (r) of 0.924. Upon optimization of all factors affecting olive oil quality, the majority of the EVOOs from the Epirus region have the potential to be characterized as high in phenolic content.

Ruthenium-Cyclopentadienyl-Cycloparaphenylene Complexes: Sizable Multicharged Cations Exhibiting High DNA-Binding Affinity and Remarkable Cytotoxicity.

Two novel sizable multicharged cationic complexes, of the formulae [(η6--[12]CPP)[Ru(η5--Cp)]12]Χ12 and [(η6--[11]CPP)[Ru(η5--Cp)]11]Χ11, CPP = cycloparaphenylene, Cp = cyclopentadienyl, X = [PF6]-, (1), (3) and [Cl]-, (2), (4), were synthesized and characterized using NMR techniques, high-resolution mass spectrometry, and elemental analyses. Complexes (1) and (3) were stable in acetone and acetonitrile solutions over 48 h. In contrast, the water-soluble (2) and (4) begin to decompose in aqueous media after 1 h, due to the [Cl]- tendency for nucleophilic attack on ruthenium of the {Ru(η5--Cp)} units. Fluorescence quenching experiments conducted during the stability window of (2) with the d(5'-CGCGAATTCGCG-3')2-EtBr adducts revealed remarkably high values for Ksv = 1.185 × 104 ± 0.025 M-1 and Kb = 3.162 × 105 ± 0.001 M-1. Furthermore, the cytotoxic activity of (2) against A2780, A2780res, and MCF-7 cancer cell lines shows that it is highly cytotoxic with IC50 values in the range of 4.76 ± 1.85 to 16 ± 0.81 µΜ.

Synthesis and Characterization of Ruthenium-Paraphenylene-Cyclopentadienyl Full-Sandwich Complexes: Cytotoxic Activity against A549 Lung Cancer Cell Line and DNA Binding Properties.

Novel full-sandwich (η5-Cp)-Ru-paraphenylene complexes with the general formula [(η5-Cp)nRu(η6-L)](PF6)n where n = 1-3 and L = biphenyl, p-terphenyl and p-quaterphenyl, were synthesized and characterized by means of spectroscopic and analytical techniques. The structures of the complexes [(η5-Cp)Ru(η6-biphenyl)](PF6) (1), [(η5-Cp)Ru(η6-terphenyl)](PF6) (3) and [(η5-Cp)2Ru(η6-terphenyl)](PF6)2 (4) was determined by X-ray single crystal methods. The interaction of the complexes [(η5-Cp)Ru(η6-quaterphenyl)]Cl, (6)Cl, and [(η5-Cp)2Ru(η6-quaterphenyl)]Cl2, (7)Cl2, with the DNA duplex d(5'-CGCGAATTCGCG-3')2 was studied using NMR techniques. The results showed that both complexes interacted non-specifically with both the minor and major grooves of the helix. Specifically, (6)Cl exhibited partial binding through intercalation between the T7 and T8 bases of the sequence without disrupting the C-G and A-T hydrogen bonds. Fluorometric determination of the complexes' binding constants revealed a significant influence of the number of connected phenyl rings in the paraphenylene ligand (L) on the binding affinity of their complexes with the d(5'-CGCGAATTCGCG-3')2. The complexes (6)Cl and (7)Cl2 were found to be highly cytotoxic against the A549 lung cancer cell line, with complex (6) being more effective than (7) (IC50 for (6)Cl: 17.45 ± 2.1 µΜ, IC50 for (7)Cl2: 65.83 ± 1.8 µΜ) and with a selectivity index (SI) (SI for (6)Cl: 1.1 and SI for (7)Cl2: 4.8).