Search Results (42)

A pseudo-multicomponent one-pot protocol for the synthesis of 1,3-disubstituted imidazolidin-2-one is described, employing trans-(R,R)-diaminocyclohexane for the in situ formation of the Schiff base, followed by reduction to produce the respective diamine and cyclization with carbonyldiimidazole (CDI). This approach utilizes statistical analysis to optimize the reaction conditions, allowing a pseudo-multicomponent protocol to be proposed. The developed method demonstrates sustainability, efficiency, and potential applications in green chemistry, achieving yields ranging from 55% to 81%. This represents a significant advance in synthesizing heterocyclic compounds with biological and pharmacological applications. Full article

Transition metal complexes have been used in medicine for several decades, but their intracellular effects are not yet fully elucidated. Therefore, in this study, we investigate biomolecular changes induced by a palladium(II) complex in cervical carcinoma (HeLa) cells as a model to study the subtle changes caused by transition metal ions ingested by the cells. The impact of dichloro(1,2-diaminocyclohexane)palladium(II), [Pd(dach)Cl₂], was studied by synchrotron radiation-based Fourier transform infrared (SR FTIR) spectroscopy, a powerful tool for studying alterations in cellular components’ biochemical composition and biomolecular secondary structure on a single-cell level. A spectral analysis, complemented by statistics, revealed that the Pd(II) complex considerably affected all major types of macromolecules in HeLa cells and induced structural changes in proteins through an increased formation of cross-β-sheets and causes structural rearrangement in deoxyribonucleic acid (DNA) through potential chromosome fragmentation. Although a certain level of lipid peroxidation was detectable by SR FTIR spectroscopy and confirmed by an analysis of cellular lipids by matrix-assisted laser desorption and ionisation time-of-flight mass spectrometry, the oxidative stress is not a significant mechanism by which Pd(II) expresses the effect on the HeLa cells. Full article

A comparative study of the copolymerization of racemic propylene oxide (PO) with CO₂ catalyzed by racemic (salcy)CoX (salcy = N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-diaminocyclohexane; X = perfluorobenzoate (OBzF₅) or 2,4-dinitrophenoxy (DNP)) in the presence of a [PPN]Cl ([PPN] = bis(triphenylphosphine)iminium) cocatalyst is performed in bulk at 21 °C and a 2.5 MPa pressure of CO₂. The increase in the nucleophilicity of an attacking anion results in the increase in the copolymerization rate. Racemic (salcy)CoX provides a high selectivity of the copolymerization, which can be higher than 99%, and the living polymerization mechanism. Poly(propylene carbonate) (PPC) with bimodal molecular weight distribution (MWD) is formed throughout copolymerization. Both modes are living and are characterized by low dispersity, while their contribution to MWD depends on the nature of the attacking anion. The racemic (salcy)CoDNP/[PPN]DNP system is found to be preferable for the production of PPC with a high yield and selectivity. Full article

Development of resistance to cisplatin, oxaliplatin and carboplatin remains a challenge for their use as chemotherapies, particularly in breast and colorectal cancer. Here, we compare the anticancer effect of novel complexes [Pt(1,10-phenanthroline)(1S,2S-diaminocyclohexane)](NO₃)₂ (Pt^IIPHENSS), [Pt(5-methyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)](NO₃)₂ (Pt^II5MESS) and [Pt(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)](NO₃)₂ (Pt^II56MESS) and their platinum(IV)-dihydroxy derivatives with cisplatin. Complexes are greater than 11-fold more potent than cisplatin in both 2D and 3D cell line cultures with increased selectivity for cancer cells over genetically stable cells. ICP-MS studies showed cellular uptake occurred through an active transport mechanism with considerably altered platinum concentrations found in the cytoskeleton across all complexes after 24 h. Significant reactive oxygen species generation was observed, with reduced mitochondrial membrane potential at 72 h of treatment. Late apoptosis/necrosis was shown by Annexin V-FITC/PI flow cytometry assay, accompanied by increased sub-G0/G1 cells compared with untreated cells. An increase in S and G2+M cells was seen with all complexes. Treatment resulted in significant changes in actin and tubulin staining. Intrinsic and extrinsic apoptosis markers, MAPK/ERK and PI3K/AKT activation markers, together with autophagy markers showed significant activation of these pathways by Western blot. The proteomic profile investigated post-72 h of treatment identified 1597 MDA−MB−231 and 1859 HT29 proteins quantified by mass spectroscopy, with several differentially expressed proteins relative to no treatment. GO enrichment analysis revealed a statistically significant enrichment of RNA/DNA-associated proteins in both the cell lines and specific additional processes for individual drugs. This study shows that these novel agents function as multi-mechanistic chemotherapeutics, offering promising anticancer potential, and thereby supporting further research into their application as cancer therapeutics. Full article

It is generally accepted that adjacent guanine residues in DNA are the primary target for platinum antitumor drugs and that differences in the conformations of the Pt-DNA adducts can play a role in their antitumor activity. In this study, we investigated the effect of the carrier ligand cis-1,3-diaminocyclohexane (cis-1,3-DACH) upon formation, stability, and stereochemistry of the (cis-1,3-DACH)PtG₂ and (cis-1,3-DACH)Pt(d(GpG)) adducts (G = 9-EthlyGuanine, guanosine, 5′- and 3′-guanosine monophosphate; d(GpG) = deoxyguanosil(3′-5′)deoxyguanosine). A peculiar feature of the cis-1,3-DACH carrier ligand is the steric bulk of the diamine, which is asymmetric with respect to the Pt-coordination plane. The (cis-1,3-DACH)Pt(5′GMP)₂ and (cis-1,3-DACH)Pt(3′GMP)₂ adducts show preference for the ΛHT and ∆HT conformations, respectively (HT stands for Head-to-Tail). Moreover, the increased intensity of the circular dichroism signals in the cis-1,3-DACH derivatives with respect to the analogous cis-(NH₃)₂ species could be a consequence of the greater bite angle of the cis-1,3-DACH carrier ligand with respect to cis-(NH₃)₂. Finally, the (cis-1,3-DACH)Pt(d(GpG)) adduct is present in two isomeric forms, each one giving a pair of H8 resonances linked by a NOE cross peak. The two isomers were formed in comparable amounts and had a dominance of the HH conformer but with some contribution of the ΔHT conformer which is related to the HH conformer by having the 3′-G base flipped with respect to the 5′-G residue. Full article

Chemotherapy resistance in cancer is an essential factor leading to high mortality rates. Tumor multidrug resistance arises as a result of the autophagy process. Our previous study found that compound 1-nitro-2 acyl anthraquinone-leucine (C2) exhibited excellent anti-colorectal cancer (CRC) activity involving autophagy and apoptosis-related proteins, whereas its underlying mechanism remains unclear. A notable aspect of this study is how C2 overcomes the multidrug susceptibility of HCT116/L-OHP, a colon cancer cell line that is resistant to both in vitro and in vivo oxaliplatin (trans-/-diaminocyclohexane oxalatoplatinum; L-OHP). In a xenograft tumor mouse model, we discovered that the mixture of C2 and L-OHP reversed the resistance of HCT116/L-OHP cells to L-OHP and inhibited tumor growth; furthermore, C2 down-regulated the gene expression levels of P-gp and BCRP and decreased P-gp’s drug efflux activity. It is important to note that while C2 re-sensitized the HCT116/L-OHP cells to L-OHP for apoptosis, it also triggered a protective autophagic pathway. The expression levels of cleaved caspase-3 and Beclin 1 steadily rose. Expression of PI3K, phosphorylated AKT, and mTOR were decreased, while p53 increased. We demonstrated that the anthraquinone derivative C2 acts as an L-OHP sensitizer and reverses resistance to L-OHP in HCT116/L-OHP cells. It suggests that C2 can induce autophagy in HCT116/L-OHP cells by mediating p53 and the PI3K/AKT/mTOR signaling pathway. Full article

With this report, the space group of $\left[Zn\left(Nal\right){\left(DACH\right)}_2\right]Cl$ is corrected ($Nal$: nalidixic acid mono-anion; $DACH$: diaminocyclohexane) from its wrong description in the literature. In the correct, non-centrosymmetric space group $P1$, the crystal structure is well ordered and the stereochemistry is correct. Crystallographic tools to recognize the correct symmetry are described. This work encourages experienced and inexperienced scientists to remain critical about the output of automatic, black-box crystallographic software. Full article

This review summarizes the structural characteristics and physicochemical properties of chiral 4f and 3d-4f complexes based on enantiopure salen-type Schiff base ligands. The chirality originates from the enantiopure diamines and is imparted to the Schiff base ligands and complexes and finally to the crystal structures. The reported enantiopure Schiff base ligands derive from the condensation of aromatic aldehydes, such as salicylaldehyde and its various derivatives, and the enantiopure diamines, (1R,2R) or (1S,2S)-1,2-diamino-cyclohexane, (1R,2R) or (1S,2S)-1,2-diamino-1,2-diphenylethane, (R) or (S)-2,2′-diamino-1,1′-binaphthalene, and 1,2-diaminopropane. Full article

Two bis-(imidazolium–vanillylidene)-(R,R)-diaminocyclohexane ligands (H₂(VAN)₂dach, H₂L_1,2) and their Pd(II) complexes (PdL₁ and PdL₂) were successfully synthesized and structurally characterized using microanalytical and spectral methods. Subsequently, to target the development of new effective and safe anti-breast cancer chemotherapeutic agents, these complexes were encapsulated by lipid nanoparticles (LNPs) to formulate (PdL₁LNP and PdL₂LNP), which are physicochemically and morphologically characterized. PdL₁LNP and PdL₂LNP significantly cause DNA fragmentation in MCF-7 cells, while trastuzumab has a 10% damaging activity. Additionally, the encapsulated Pd_1,2LNPs complexes activated the apoptotic mechanisms through the upregulated P53 with p < 0.001 and p < 0.05, respectively. The apoptotic activity may be triggered through the activity mechanism of the Pd_1,2LNPs in the inhibitory actions against the FGFR2/FGF2 axis on the gene level with p < 0.001 and the Her2/neu with p < 0.05 and p < 0.01. All these aspects have triggered the activity of the PdL₁LNP and PdL₂LNP to downregulate TGFβ1 by p < 0.01 for both complexes. In conclusion, LNP-encapsulated Pd(II) complexes can be employed as anti-cancer drugs with additional benefits in regulating the signal mechanisms of the apoptotic mechanisms among breast cancer cells with chemotherapeutic-safe actions. Full article

Cisplatin-type covalent chemotherapeutics are a cornerstone of modern medicinal oncology. However, these drugs remain encumbered with dose-limiting side effects and are susceptible to innate and acquired resistance. The bulk of platinum anticancer research has focused on Cisplatin and its derivatives. Here, we take inspiration from the design of platinum complexes and ligands used successfully with other metals to create six novel complexes. Herein, the synthesis, characterization, DNA binding affinities, and lipophilicity of a series of non-traditional organometallic Pt(II)-complexes are described. These complexes have a basic [Pt(P_L)(A_L)]Cl₂ molecular formula which incorporates either 2-pyrrolidin-2-ylpyridine, 2-(1H-Imidazol-2-yl)pyridine, or 2-(2-pyridyl)benzimidazole as the P_L; the A_L is resolved diaminocyclohexane. Precursor [Pt(P_L)(Cl)₂] complexes were also characterized for comparison. While the cytotoxicity and DNA binding properties of the three precursors were unexceptional, the corresponding [Pt(P_L)(A_L)]²⁺ complexes were promising; they exhibited different DNA binding interactions compared with Cisplatin but with similar, if not slightly better, cytotoxicity results. Complexes with 2-pyrrolidin-2-ylpyridine or 2-(2-pyridyl)benzimidazole ligands had similar DNA binding properties to those with 2-(1H-Imidazol-2-yl)pyridine ligands but were not as cytotoxic to all cell lines. The variation in activity between cell lines was remarkable and resulted in significant selectivity indices in MCF10A and MCF-7 breast cancer cell lines, compared with previously described similar Pt(II) complexes such as 56MESS. Full article

Mechanically separated meat (MSM) is a by-product of the poultry industry that requires routine quality assessment. Calcium content is an indirect indicator of bone debris in MSM but is difficult to determine by EDTA titration due to the poor solubility of calcium phosphate. Therefore, 1,2-diaminocyclohexane-N,N,N’,N’-tetraacetic acid was used instead, which has two orders of magnitude higher affinity for calcium ions. In addition, the auxiliary complexing agents triethanolamine and Arsenazo III, an indicator that is sensitive to low calcium concentrations, were used. Automatic titration endpoint detection was performed using an immersion probe at 660 nm. It has been shown that the color change in Arsenazo III can also be read with an RGB camera. The CDTA titration procedure has been tested on commercial Bologna-type sausages and the results were in line with AAS and ICP reference data. The content of calcium in sausages turned out to be very diverse and weakly correlated with the content of MSM. The tested MSM samples had a wide range of calcium content: from 62 to 2833 ppm. Calcium-rich poultry by-products include fat and skin (115 to 412 ppm), articular cartilage (1069 to 1704 ppm), and tendons (532 to 34,539 ppm). The CDTA titration procedure is fully suitable for small meat processing plants due to its simplicity of use and low cost. Full article

A new series of nanostructured materials was obtained by functionalization of SBA-15 mesoporous silica with Ru(II) and Ru(III) complexes bearing Schiff base ligands derived from salicylaldehyde and various amines (1,2-diaminocyclohexane, 1,2-phenylenediamine, ethylenediamine, 1,3-diamino-2-propanol, N,N-dimethylethylenediamine, 2-aminomethyl-pyridine, and 2-(2-aminoethyl)-pyridine). The incorporation of ruthenium complexes into the porous structure of SBA-15 and the structural, morphological, and textural features of the resulting nanostructured materials were investigated by FTIR, XPS, TG/DTA, zeta potential, SEM, and N₂ physisorption. The ruthenium complex-loaded SBA-15 silica samples were tested against A549 lung tumor cells and MRC-5 normal lung fibroblasts. A dose-dependent effect was observed, with the highest antitumoral efficiency being recorded for the material containing [Ru(Salen)(PPh₃)Cl] (50%/90% decrease in the A549 cells’ viability at a concentration of 70 μg/mL/200 μg/mL after 24 h incubation). The other hybrid materials have also shown good cytotoxicity against cancer cells, depending on the ligand included in the ruthenium complex. The antibacterial assay revealed an inhibitory effect for all samples, the most active being those containing [Ru(Salen)(PPh₃)Cl], [Ru(Saldiam)(PPh₃)Cl], and [Ru(Salaepy)(PPh₃)Cl], especially against Staphylococcus aureus and Enterococcus faecalis Gram-positive strains. In conclusion, these nanostructured hybrid materials could represent valuable tools for the development of multi-pharmacologically active compounds with antiproliferative, antibacterial, and antibiofilm activity. Full article

Cancer poses a significant threat to global health and new treatments are required to improve the prognosis for patients. Previously, unconventional platinum complexes designed to incorporate polypyridyl ligands paired with diaminocyclohexane have demonstrated anticancer activity in KRAS mutated cells, previously thought to be undruggable and have cytotoxicity values up to 100 times better than cisplatin. In this work, these complexes were used as inspiration to design six novel cyclometallated examples, whose fluorescence could be exploited to better understand the mechanism of action of these kinds of platinum drugs. The cytotoxicity results revealed that these cyclometallated complexes (CMCs) have significantly different activity compared to the complexes that inspired them; they are as cytotoxic as cisplatin and have much higher selectivity indices in breast cancer cell lines (MCF10A/MCF-7). Complexes 1b, 2a, and 3b all had very high selectivity indexes compared to previous Pt(II) complexes. This prompted further investigation into their DNA binding properties, which revealed that they had good affinity to ctDNA, especially CMCs 1a and 3b. Their inherent fluorescence was successfully utilised in the calculation of their DNA binding affinity and could be useful in future work. Full article

Al(III) complexes have been recently investigated for their potential use in imaging with positron emission tomography (PET) by formation of ternary complexes with the radioisotope fluorine-18 (¹⁸F). Although the derivatives of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) are the most applied chelators for [Al¹⁸F]²⁺ labelling and (pre)clinical PET imaging, non-macrocyclic, semi-rigid pentadentate chelators having two N- and three O-donor atoms such as RESCA1 and AMPDA-HB have been proposed with the aim to allow room temperature labelling of temperature-sensitive biomolecules. The paucity of stability data on Al(III) complexes used for PET imaging instigated a complete thermodynamic and kinetic solution study on Al(III) complexes with aminomethylpiperidine (AMP) derivatives AMPTA and AMPDA-HB and the comparison with a RESCA1-like chelator CD3A-Bn (trans-1,2-diaminocyclohexane-N-benzyl-N,N′,N′-triacetic acid). The stability constant of [Al(AMPDA-HB)] is about four orders of magnitude higher than that of [Al(AMPTA)] and [Al(CD3A-Bn)], highlighting the greater affinity of phenolates with respect to acetate O-donors. On the other hand, the kinetic inertness of the complexes, determined by following the Cu²⁺-mediated transmetallation reactions in the 7.5–10.5 pH range, resulted in a spontaneous and hydroxide-assisted dissociation slightly faster for [Al(AMPTA)] than for the other two complexes (t_1/2 = 4.5 h for [Al(AMPTA)], 12.4 h for [Al(AMPDA-HB)], and 24.1 h for [Al(CD3A-Bn)] at pH 7.4 and 25 °C). Finally, the [AlF]²⁺ ternary complexes were prepared and their stability in reconstituted human serum was determined by ¹⁹F NMR experiments. Full article