Exploring the cytotoxicity of dinuclear Ru(II) p-cymene complexes appended N,N'-bis(4-substituted benzoyl)hydrazines: insights into the mechanism of apoptotic cell death.

Cancer is a perilous life-threatening disease, and attempts are constantly being made to create multinuclear transition metal complexes that could lead to the development of potential anticancer medications and administration procedures. Hence, this work aims to design, synthesize, characterize, and assess the anticancer efficacy of ruthenium p-cymene complexes incorporating N,N'-bis(4-substituted benzoyl)hydrazine ligands. The formation of the new complexes (Ru2H1-Ru2H3) has been thoroughly established by elemental analysis, and FT-IR, UV-vis, NMR, and HR-MS spectral techniques. The solid-state molecular structures of the complexes Ru2H1 and Ru2H3 have been determined using the SC-XRD study, which confirms the N, O, and Cl-legged piano stool pseudo-octahedral geometry of each ruthenium(II) ion. The stability of these complexes in the solution state and their lipophilicity profile have been determined. Furthermore, the title complexes were tested for their in vitro anticancer activity against cancerous H460 (lung cancer cells), SkBr3 (breast cancer cells), HepG2 (liver cancer cells), and HeLa (cervical cancer cells) along with non-cancerous (HEK-293) cells. The IC50 results revealed that complex Ru2H3 exhibits potent activity against the proliferation of all four cancer cells and outscored the effect of the standard metallodrug cisplatin. This may be attributed to the presence of a couple of lipophilic electron-donating methoxy groups in the ligand scaffold and also the ruthenium(II) p-cymene motifs. Advantageously, all the complexes (Ru2H1-Ru2H3) displayed cytotoxic specificity only towards cancerous cells by leaving the off-target non-cancerous cells undamaged. Acridine orange/ethidium bromide (AO/EB) staining, Hoechst 33342, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) staining assays were used to investigate the apoptotic pathway and ROS levels in mitochondria. The results of western blot analysis confirmed that the complexes triggered apoptosis through an intrinsic mitochondrial pathway by upregulating Bax and downregulating Bcl-2 proteins. Finally, the extent of apoptosis triggered by the complex Ru2H3 was quantified with the aid of flow cytometry using the Annexin V-FITC/propidium iodide (PI) double-staining technique.

Effect of N-phenyl substituent on thermal, optical, electrochemical and luminescence properties of 3-aminophthalimide derivatives.

The seven N-phthalimide derivatives substituted with the amine group at the 3-C position in the phenylene ring were synthesized. The effect of N-substituent chemical structure was investigated. The thermal, electrochemical and optical studies were performed and supported by the density functional theory calculations (DFT). The electrochemical investigations of the synthesized low-molecular phthalimides revealed the one oxidation and reduction process with the HOMO energy level under - 5.81 eV and energy-band gap below 3 eV. The N-phthalimide derivatives were emitted light in a blue spectral region in solutions (in polar and non-polar) with the quantum yield between 2 and 68%, dependent on the substituent at the nitrogen atom, solvent and concentration. The N-phthalimide derivatives were emissive also in a solid state as a thin film and powder. They were tested as a component of the active layer with PVK:PBD matrix and as an independent active layer in the organic light-emitting diodes. The registered electroluminescence spectra exhibited the maximum emission band in the 469-505 nm range, confirming the possibility of using N-phthalimides with PVK:PBD matrix as the blue emitters.

Room-Temperature Synthesis of Biogenic δ-MnO2 NPs for the Dehydrogenative Coupling of Diamines with Alcohols for Benzimidazole and Quinoxaline Synthesis: An Efficient Catalyst for Electrochemical Applications.

An efficient, unique, and eco-friendly biogenic synthesis of single-crystalline δ-phase manganese oxide nanoparticles (MnO2 NPs) using Gliricidia sepium leaves (GSL) extract at room temperature has been revealed for the first time. The active chemicals present in the GSL extract were found to serve as both reducing and stabilizing agents. The catalyst shows an excellent surface area of 301.13 m2 g-1, a mean pore diameter of 4.01 nm, and 39.97% w/w of active metal content. The reactivity of the synthesized catalyst was demonstrated by achieving a one-pot synthesis of benzimidazoles and quinoxalines via an acceptorless dehydrogenative coupling strategy utilizing biorenewable alcohols. The release of hydrogen gas was observed as the only side product and proven by its successful utilization for alkene reduction which supports the mechanistic elucidation. The release of hydrogen gas as a useful byproduct highlights the scientific importance of the present methodology. Additionally, gram-scale synthesis and catalyst recyclability studies are deliberated. Importantly, the δ-MnO2 NP catalyst exhibited superior catalytic activity and high durability toward hydrogen evolution reaction in alkaline media, highlighting the dual use of the catalyst. The δ-MnO2 NPs attain the current density of 10 mA/cm2 at an overpotential of 154 mV with a Tafel slope of 119 mV/dec.

Exploration of Antiproliferative Activity and Apoptosis Induction of New Nickel(II) Complexes Encompassing Carbazole Ligands.

To attest the effectiveness of nickel complexes as anticancer drug candidates with minimum side effects, the present investigation describes the facile synthesis and anticancer activities of nickel(II) complexes enriched with three derivatives of carbazolone-based benzhydrazone ligands(L) having a [Ni(L)2] composition. Analytical and spectral techniques were used to characterize the synthesized Ni(II) complexes. The single-crystal X-ray diffraction performed for complex 4 confirmed the square planar geometry with a [Ni(κ2-N,O-L)2] arrangement. The MTT assay was carried out for the complexes to determine in vitro cytotoxicity against cancerous human-cervical carcinoma, human-colon carcinoma, and non-cancerous L929 (fibroblast) cells. All three complexes exhibited good toxicity against the cancer cells with a low IC50 concentration. Complex 4, containing -OCH3 fragment, exhibits high lipophilicity and revealed exceptional cytotoxicity against cancer cells. AO-EB fluorescent staining indicated apoptosis-associated cell morphological changes after exposure to complex 4. The apoptosis induction was further confirmed by a HOECHST-33342 fluorescent staining technique via chromosomal condensation and nuclear fragmentation. Further, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) mechanistic studies revealed that complex 4 can raise ROS levels and reduce MMP and promote mitochondrial dysfunction-mediated apoptotic cell death. Further, stimulation of late apoptosis by complex 4 in cervical cancer cells was quantitatively differentiated through the staining of phosphatidylserine externalization by flow cytometry. Furthermore, the ELISA analysis confirmed that complex 4 induced apoptosis through caspase activation.

Sugar-Based Phase-Selective Supramolecular Self-Assembly System for Dye Removal and Selective Detection of Cu2+ Ions.

Simple, effective, and eco-friendly sugar-based phase-selective gelators were synthesized at a low cost. They showed high gelling ability toward a wide range of solvents at lower concentrations (minimum gelation concentration ∼0.3%). Preliminary tests reveal that these low molecular weight organogelators can immediately and phase-selectively gel benzene, toluene, petrol, and kerosene in water at room temperature. We also identified G13 in toluene as the good gelator, and the corresponding organogel proficiently removes water-soluble dyes from their concentrated aqueous solutions. This efficient removal of toxic organic solvents and dyes from water suggests promising applications in removing organic substances from contaminated water resources. The thermoreversible gel exhibits effective rechargeability up to five cycles of burning and gelation, which imply the flame stability of the gel. Interestingly, these compounds had a high detection ability toward Cu2+ ions with a state change from gel to the solution. The physical justification for gelation mechanisms and the molecular interaction with metal ions were further confirmed by computational studies.

Six New Unsymmetrical Imino-1,8-naphthalimide Derivatives Substituted at 3-C Position-Photophysical Investigations.

In this research, six novel unsymmetrical imino-1,8-naphthalimides (AzNI) were synthesized. Comprehensive thermal (thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), optical (UV-Vis, photoluminescence), and electrochemical (CV, DPV) studies were carried out to characterize these new compounds. The molecules showed the onset of thermal decomposition in the temperature range 283-372 °C and molecular glass behavior. Imino-1,8-naphthalimides underwent reduction and oxidation processes with the electrochemical energy band gap (Eg) below 2.41 eV. The optical properties were evaluated in solvents with different polarities and in the solid-state as a thin films and binary blends with poly(N-vinylcarbazole): (2-tert-butylphenyl-5-biphenyl-1,3,4-oxadiazole) (PVK:PBD). Presented compounds emitted blue light in the solutions and in the green or violet spectral range in the solid-state. Their ability to emit light under external voltage was examined. The devices with guest-host structure emitted light with the maximum located in the blue to red spectral range of the electroluminescence band (EL) depending on the content of the AzNI in the PVK:PBD matrix (guest-host structure).

Spectroscopic and Physicochemical Investigations of Azomethines with Triphenylamine Core towards Optoelectronics.

Three new azomethines based on triphenylamine with two or three substituents were obtained. Chemical structure and purity were confirmed by 1H NMR, FTIR elemental analysis and mass spectroscopy. The investigations were focused on the relationship between chemical structure and properties important for optoelectronic materials. Thus, the studies of thermal, optical and electrochemical properties were carried out based on differential scanning calorimetry, thermogravimetric analysis, electronic absorption, photoluminescence and cyclic voltammetry measurements. The ongoing consideration of experimental results was complemented by theoretical calculations using the density functional theory method. The donor activity of obtained compounds was tested in bulk-heterojuntion photovoltaic cells with structure ITO/PEDOT:PSS/imine:PCBM/Al and ITO/PEDOT:PSS/imine:P3HT:PCBM/Al). The effect of the presence of the amino-thiophene-3,4-dicarboxylic acid diethyl ester groups and various number of hexyloxyphenyl units on imines properties was demonstrated.

Synthesis and Characterization of New Conjugated Azomethines End-Capped with Amino-thiophene-3,4-dicarboxylic Acid Diethyl Ester.

A new series of thiophene-based azomethines differing in the core structure was synthesized. The effect of the central core structure in azomethines on the thermal, optical and electrochemical properties was investigated. The obtained compounds exhibited the ability to form a stable amorphous phase with a high glass transition temperature above 100 °C. They were electrochemically active and undergo oxidation and reduction processes. The highest occupied (HOMO) and the lowest unoccupied molecular (LUMO) orbitals were in the range of -3.86--3.60 eV and -5.46--5.17 eV, respectively, resulting in a very low energy band gap below 1.7 eV. Optical investigations were performed in the solvents with various polarity and in the solid state as a thin film deposited on a glass substrate. The synthesized imines absorbed radiation from 350 to 600 nm, depending on its structure and showed weak emission with a photoluminescence quantum yield below 2.5%. The photophysical investigations were supported by theoretical calculations using the density functional theory. The synthesized imines doped with lithium bis-(trifluoromethanesulfonyl)imide were examined as hole transporting materials (HTM) in hybrid inorganic-organic perovskite solar cells. It was found that both a volume of lithium salt and core imine structure significantly impact device performance. The best power conversion efficiency (PCE), being about 35-63% higher compared to other devices, exhibited cells based on the imine containing a core tiphenylamine unit.

Synthesis and Thermal, Photophysical, Electrochemical Properties of 3,3-di[3-Arylcarbazol-9-ylmethyl]oxetane Derivatives.

Novel oxetane-functionalized derivatives were synthesized to find the impact of carbazole substituents, such as 1-naphtyl, 9-ethylcarbazole and 4-(diphenylamino)phenyl, on their thermal, photophysical and electrochemical properties. Additionally, to obtain the optimized ground-state geometry and distribution of the frontier molecular orbital energy levels, density functional theory (DFT) calculations were used. Thermal investigations showed that the obtained compounds are highly thermally stable up to 360 °C, as molecular glasses with glass transition temperatures in the range of 142-165 °C. UV-Vis and photoluminescence studies were performed in solvents of differing in polarity, in the solid state as a thin film on glass substrate, and in powders, and were supported by DFT calculations. They emitted radiation both in solution and in film with photoluminescence quantum yield from 4% to 87%. Cyclic voltammetry measurements revealed that the materials undergo an oxidation process. Next, the synthesized molecules were tested as hole transporting materials (HTM) in perovskite solar cells with the structure FTO/b-TiO2/m-TiO2/perovskite/HTM/Au, and photovoltaic parameters were compared with the reference device without the oxetane derivatives.

New Benzo[h]quinolin-10-ol Derivatives as Co-sensitizers for DSSCs.

New benzo[h]quinolin-10-ol derivatives with one or two 2-cyanoacrylic acid units were synthesized with a good yield in a one-step condensation reaction. Chemical structure and purity were confirmed using NMR spectroscopy and elemental analysis, respectively. The investigation of their thermal, electrochemical and optical properties was carried out based on differential scanning calorimetry, cyclic voltammetry, electronic absorption and photoluminescence measurements. The analysis of the optical, electrochemical and properties was supported by density functional theory studies. The synthesized molecules were applied in dye-sensitized solar cells as sensitizers and co-sensitizers with commercial N719. The thickness and surface morphology of prepared photoanodes was studied using optical, scanning electron and atomic force microscopes. Due to the utilization of benzo[h]quinolin-10-ol derivatives as co-sensitizers, the better photovoltaic performance of fabricated devices compared to a reference cell based on a neat N719 was demonstrated. Additionally, the effect of co-adsorbent chemical structure (cholic acid, deoxycholic acid and chenodeoxycholic acid) on DSSC efficiency was explained based on the density functional theory.

New Acceptor-Donor-Acceptor Systems Based on Bis-(Imino-1,8-Naphthalimide).

In this paper, six novel symmetrical bis-(imino-1,8-naphthalimides) differing in core and N-substituent structure were synthesized, and their thermal (TGA, DSC), optical (UV-Vis, PL), electrochemical (DPV, CV) properties were evaluated. The compounds were stable to 280 °C and could be transferred into amorphous materials. Electrochemical investigations showed their ability to occur reductions and oxidations processes. They exhibited deep LUMO levels of about -3.22 eV and HOMO levels above -5.80 eV. The optical investigations were carried out in the solutions (polar and non-polar) and in films and blends with PVK:PBD. Bis-(imino-1,8-naphthalimides) absorbed electromagnetic radiation in the range of 243-415 nm and emitted light from blue to yellow. Their capacity for light emission under voltage was preliminarily tested in devices with an active layer consisting of a neat compound and a blend with PVK:PBD. The diodes emitted green or red light.

Water-Soluble Pyrene-Adorned Imidazolium Salts with Multicolor Solid-State Fluorescence: Synthesis, Structure, Photophysical Properties, and Application on the Detection of Latent Fingerprints.

New water-soluble acetylpyrene-bound imidazolium salts (1-N-methyl-3-(2-oxo-2-(pyren-1-yl)ethyl)-imidazolium bromide (1), 1-N-isopropyl-3-(2-oxo-2-(pyren-1-yl)ethyl)-imidazolium bromide (2), 1-N-allyl-3-(2-oxo-2-(pyren-1-yl)ethyl)-imidazolium bromide (3), and 1-N-isopropyl-3-(2-oxo-2-(pyren-1-yl)ethyl)-imidazolium hexafluorophosphate (4)) were synthesized from the reaction between 1-bromoacetylpyrene and N-substituted imidazoles in excellent yield. The new molecules were fully characterized by elemental analysis, FT-IR, multinuclear (1H, 13C, and 19F) NMR techniques, and single-crystal X-ray diffraction analysis. Investigations on the crystal packing of 1, 3, and 4 show the presence of inter/intramolecular weak interactions, including the π···π stacking interaction between the pairs of pyrene molecules. The photophysical properties were investigated in detail for the four imidazolium salts. Experiments show that the emissions observed for all the four compounds are due to the excited monomer and static excimer. Very interestingly, all the four compounds exhibit solid-state multicolor fluorescence depending on the excitation wavelength. The solid-state emissions were monitored using a fluorescence microscope. Finally, a fingerprint powder was formulated based on compound 4 and demonstrated as an efficient fluorescent fingerprint powder for forensic applications. The formulated powder revealed all the 3 level information along with peculiar individual characteristics of the fingerprints under investigation. The fingerprints were further viewed through a fluorescence microscope, and the results were discussed in detail.

Direct Amination of Nitroquinoline Derivatives via Nucleophilic Displacement of Aromatic Hydrogen.

The vicarious nucleophilic substitution of hydrogen (VNS) reaction in electron-deficient nitroquinolines was studied. Properties of all new products have been characterized by several techniques: MS, HRMS, FTIR, GC-MS, electronic absorption spectroscopy, and multinuclear NMR. The structures of 4-chloro-8-nitroquinoline, 8-(tert-butyl)-2-methyl-5-nitroquinoline, 9-(8-nitroquinolin-7-yl)-9H-carbazole and (Z)-7-(9H-carbazol-9-yl)-8-(hydroxyimino)quinolin-5(8H)-one were determined by single-crystal X-ray diffraction measurements. The 9-(8-nitroquinolin-7-yl)-9H-carbazole and (Z)-7-(9H-carbazol-9-yl)-8-(hydroxyimino)quinolin-5(8H)-one illustrate the nitro/nitroso conversion within VNS reaction. Additionally, 9-(8-isopropyl-2-((8-isopropyl-2-methyl-5-nitroquinolin-6-yl)methyl)-5-nitrosoquinolin-6-yl)-9H-carbazole is presented as a double VNS product. It is postulated that the potassium counterion interacts with the oxygen on the nitro group, which could influence nucleophile attack in that way.

Hydrolysis of Schiff bases with phenyl-ethynyl-phenyl system: The importance for biological and physicochemical studies.

A series of new Schiff bases containing the phenyl-ethynyl-phenyl system was synthesized and their thermal stability, photophysical and electrochemical properties were investigated. Moreover, DFT calculations were performed to obtain the optimized ground-state geometry and distribution of the HOMO and LUMO levels as well as IR spectra of the prepared compounds. It was found that, the photoluminescence of synthesized imines was negligible in all investigated organic solvents except for the PBS/ACN mixture. As was proved in further studies, this phenomenon was related to the partial hydrolysis of imines, which is the source of the fluorogenic aldehyde causing the aggreggacion incrased-emision effect. In further research, due to the susceptibility of the azomethines to partial hydrolysis, the biological activity of 2-{(E)-[4-(phenylethynyl) phenyl]imino}phenol (1b), substrate (2-aminophenol) and Cu(II)-1b complex was analyzed. The biological tests showed, that 1b (as example of imine resveratrol analogue), demonstrated its increased cytostatic activity in prostate cancer cellular system. It was proved that the non-hydrolyzed imine was crucial for the cytotoxic effect. This activity could be ascribed to its Cu(II) complexing capability as showed in our previous research.

Investigation into antiproliferative activity and apoptosis mechanism of new arene Ru(ii) carbazole-based hydrazone complexes.

Ruthenium complexes with bioactive ligands are becoming promising substitutes for platinum complexes due to their precise action against various cancers. In the present study, the synthesis of three new arene Ru(ii) complexes containing new carbazole-based hydrazone ligands of general formula [(η6-benzene)Ru(L)Cl] (1-3; L = carbazolone benzhydrazone ligands), and their anticancer properties are described. The structural characterization of the ligands and their ruthenium complexes has been realized with the aid of elemental analysis, IR, UV-vis, NMR and HR-MS techniques. The molecular structures of all three complexes have been elucidated by single crystal X-ray crystallography and reveal the existence of pseudo-octahedral geometry around the ruthenium. The in vitro cancer cell growth inhibition property of the complexes against A549 (lung carcinoma), A2780 (ovarian adenocarcinoma) and non-cancerous 16HBE (human lung bronchial epithelium) cells were examined by MTT assay. All the complexes display good cytotoxicity towards both of these types of cancer cell compared to the standard drug cisplatin, with low IC50 values. Remarkably, complex 3, which contains an electron-donating substituent, induces a significant reduction of viability in A2780 cells. The inhibition capacity of the complexes towards A2780 cells proliferation was further confirmed using 5-ethynyl-2-deoxyuridine (EdU) assay via minimal DNA synthesis. The result of the acridine orange-ethidium bromide (AO-EB) fluorescent staining assay establishes that the cytotoxicity of the complexes was mediated by apoptosis in cancer cells. Furthermore, flow cytometry using Annexin V-FITC/propidium iodide (PI) double staining determines the quantitative discrimination of early apoptosis by the externalization of phosphatidylserine. In addition, cell cycle distribution indicates that the complexes block the cell cycle progression in the S-phase. The outcome of our investigation shows the promising scope and potency of tailored arene ruthenium complexes for precise cancer chemotherapy beyond platinum drugs.

Conformational analysis and molecular dynamics of glass-forming aromatic thiacrown ethers.

In this work, we report the synthesis, unexpected glass-forming properties, molecular dynamics and conformational analysis of two thiacrown ethers: 6-methyl-2,3-dihydro-1,4-benzodithiine (1), with a six-membered heterocyclic ring, and macrocyclic 2,3-(4'-methylbenzo)-1,4-dithia-7-oxacyclononane (2). Based on the calorimetric studies, we showed that compound 1 is a viscous liquid at room temperature undergoing vitrification at 192 K. Compound 2 is a crystalline solid at room temperature characterized by a melting point at 331 K; however, it can be vitrified with ease after being melted by cooling down to 224 K. This gave us the unique possibility to analyze the dielectric response and to follow the molecular dynamics in supercooled liquid and glassy states for each thiacrown ether. Two relaxation processes were found for compound 1, which are structural α-relaxation, connected with the collective rotational motions of molecules in a liquid, and a low-temperature secondary γ-process, resulting from conformational changes in the heterocyclic ring. Beside these two relaxation processes, an additional intermolecular ß-process of JG type was detected in the case of compound 2. Finally, based on the analysis of the thermal evolution of the Kirkwood-Fröhlich factor, it has also been shown that thiacrown ethers may be characterized by a local ordering between neighboring molecules in the supercooled liquid state.

Nickel(II)-NΛNΛO Pincer Type Complex-Catalyzed N-alkylation of Amines with Alcohols via the Hydrogen Autotransfer Reaction.

A highly sustainable catalytic protocol for the coupling of alcohols and amines for selective monoalkylated amines using Ni(II)-NΛNΛO pincer type complexes through the borrowing hydrogen methodology is described. An array of Ni(II) catalysts (1-3) was synthesized and characterized by various spectral and analytical methods. Furthermore, the distorted square planar geometry of the complexes (1 and 2) was substantiated with single crystal X-ray diffraction study. The inexpensive nickel-based catalytic methodology displays a broad substrate scope for the N-alkylation of aromatic and heteroaromatic amines using a diverse range of primary alcohols with excellent yields up to 97%. The present approach is environmentally benign, which liberates water as the sole byproduct. A short synthesis of drug intermediates such as mepyramine and chloropyramine illustrates the utility of the present protocol.

APEX Strategy Represented by Diels-Alder Cycloadditions-New Opportunities for the Syntheses of Functionalised PAHs.

Diels-Alder cycloaddition of various dienophiles to the bay region of polycyclic aromatic hydrocarbons (PAHs) is a particularly effective and useful tool for the modification of the structure of PAHs and thereby their final properties. The Diels-Alder cycloaddition belongs to the single-step annulative π-extension (APEX) reactions and represents the maximum in synthetic efficiency for the constructions of π-extended PAHs including functionalised ones, nanographenes, and π-extended fused heteroarenes. Herein we report new applications of the APEX strategy for the synthesis of derivatives of 1,2-diarylbenzo[ghi]perylene, 1,2-diarylbenzo[ghi]perylenebisimide and 1,2-disubstituted-benzo[j]coronene. Namely, the so far unknown cycloaddition of 1,2-diarylacetylenes into the perylene and perylenebisimide bay regions was used. 1,2-Disubstituted-benzo[j]coronenes were obtained via cycloaddition of benzyne into 1,2-diarylbenzo[ghi]perylenes by using a new highly effective system for benzyne generation and/or high pressure conditions. Moreover, we report an unprecedented Diels-Alder cycloaddition-cycloaromatisation domino-type reaction between 1,4-(9,9-dialkylfluoren-3-yl)-1,3-butadiynes and perylene. The obtained diaryl-substituted core-extended PAHs were characterised by DFT calculation as well as electrochemical and spectroscopic measurements.

Synthesis and Electrochemical and Spectroscopic Characterization of 4,7-diamino-1,10-phenanthrolines and Their Precursors.

New approaches to the synthesis of 4,7-dichloro-1,10-phenanthrolines and their corresponding 9H-carbazol-9-yl-, 10H-phenothiazin-10-yl- and pyrrolidin-1-yl derivatives were developed. Their properties have been characterized by a combination of several techniques: MS, HRMS, GC-MS, electronic absorption spectroscopy and multinuclear NMR in both solution and solid state including 15N CP/MAS NMR. The structures of 5-fluoro-2,9-dimethyl-4,7-di(pyrrolidin-1-yl)-1,10-phenanthroline (5d), 4,7-di(9H-carbazol-9-yl)-9-oxo-9,10-dihydro-1,10-phenanthroline-5-carbonitrile (6a) and 4,7-di(10H-phenothiazin-10-yl)-1,10-phenanthroline-5-carbonitrile (6b) were determined by single-crystal X-ray diffraction measurements. The nucleophilic substitutions of hydrogen followed by oxidation produced compounds 6a and 6b. The electrochemical properties of selected 1,10-phenanthrolines were investigated using cyclic voltammetry and compared with commercially available reference 1,10-phenanthrolin-5-amine (5l). The spatial distribution of frontier molecular orbitals of the selected compounds has been calculated by density functional theory (DFT). It was shown that potentials of reduction and oxidation were in consistence with the level of HOMO and LUMO energies.

Platinum(II) coordination compounds with 4'-pyridyl functionalized 2,2':6',2″-terpyridines as an alternative to enhanced chemotherapy efficacy and reduced side-effects.

Two platinum(II) coordination compounds, [PtCl(4'-R1-terpy)](SO3CF3) (1) and [PtCl(4'-R2-terpy)](SO3CF3) (2), with 4'-(2-pyridyl)-2,2':6',2″-terpyridine (4'-R1-terpy) or 4'-(3-pyridyl)-2,2':6',2″-terpyridine (4'-R2-terpy) were synthesized and the impact of the pendant pyridyl ring on the structure and cytotoxic activity of Pt(II)-terpyridine complexes was explored. The single-crystal X-ray diffraction analysis confirmed square planar coordination of the cations [PtCl(4'-Rn-terpy)]+. The mode of binding of 1 and 2 to calf thymus DNA was examined by UV-Vis absorption titration, ethidium displacement assay and reaction with 9-ethylguanine, and the mixed covalent-intercalative mode was demonstrated. The cytotoxicity of the Pt(II) complexes against six cancer cell lines and three normal ones was determined using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and compared to cisplatin. The IC50 values for the compound 2 towards the cancer cell lines are in the low micromolar range. Most remarkably, 2 was over 4 times more effective than 1 and cisplatin against non-small lung adenocarcinoma (A549), and its selectivity index was ~60-80 times higher than that for 1 and cisplatin. The mechanisms underlying the loss of viability under treatment of 2 was further investigated including F-actin staining, mitotic index analysis, cytometric cell cycle analysis, Fluorescein isothiocyanate (FITC) -conjugated Annexin V antibody and propidium iodide (PI) staining, measurements of reactive oxygen species (ROS) in cells, analysis of changes in the mitochondrial mass and potential and quantitative real time polymerase chain reaction (qRT-PCR) genes analysis. The compound 2 was found to have a pro-oxidative effect by strong stimulation of cells for the production of reactive oxygen species and cytostatic effect through cell cycle arrest.