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Palladium(II) complexes have stimulated research interest mainly due to their in vitro cytotoxicity against various cancer cell lines and their low cytotoxicity in healthy cells. Thus, in this work, we combined Pd(II)/phosphine systems with the natural product curcumin as a ligand, obtaining a series of complexes, [Pd(cur)(PPh 3 ) 2 ]PF 6 (A1), [Pd(cur)(dppe)]PF 6 (A2), [Pd(cur)(dppp)]PF 6 (A3), [Pd(cur)(dppb)]PF 6 (A4) and [Pd(cur)(dppf)]PF 6 (A5), where dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, dppb = 1,4-bis(diphenylphosphino)butane, and dppf = 1,1'-bis(diphenylphosphino)ferrocene (P-P), which were characterized by elemental analysis, molar conductivity analysis, and mass, NMR ( 1 H, 13 C, 31 P{ 1 H}), UV-vis, and IR spectroscopies, and four of them (A1, A2, A4, and A5) by X-ray crystallography. The in vitro cell viability of the complexes A1-A5, cisplatin, and the free ligand curcumin against MDA-MB-231 (human triple-negative breast tumor cells), SK-BR-3 (human breast tumor cells), A549 (human lung tumor cells), MRC-5 (non-tumor human lung cells), A2780 (human ovarian carcinoma cells), and A2780cis (cisplatin-resistant human ovarian carcinoma cells), was evaluated by the MTT colorimetric assay. For the tumor cell lines tested, the complexes showed good anticancer activities. The results showed that in general the complexes had lower IC 50 values than free curcumin and the precursors [PdCl 2 (P-P)]. IC 50 results obtained for the A1-A5 complexes, in the MCF-7 cell line, are similar to those that had already been observed for some Pd/bipy/curcumin complexes. In the MDA-MB-231 cell line, complexes A1 and A5 stood out, with their lowest IC 50 values, around 5 μmol L -1 , and the complexes appeared to be more active (lower IC 50 values) against the ovarian cell lines. Complex A1 was 23 and 22-fold more cytotoxic than cisplatin, against the A2780 and A2780cis cells, respectively. The complex A1 was studied on A2780cis cells and it was found that this complex inhibits colony formation and induces cell cycle arrest in the sub-G1 phase in a concentration-dependent manner and leads to cell death by apoptosis. The DCFDA assay revealed a potent ROS induction for complex A1.

Herein, we present an overview of continuous flow chemistry, including photoflow and electroflow technologies in the preparation of active pharmaceutical ingredients (APIs) and fine chemical intermediates. Examples highlighting the benefits and challenges associated with continuous flow processes, mainly involving continuous thermal, photo- and electrochemical transformations, are drawn from the relevant literature, especially our experience and collaborations in this area, with emphasis on the synthesis and prospective scale-up.

A transition-metal free methodology for the chemoselective reduction of benzylidene thiazolidine-2,4-diones and similar heterocycles is described, allowing the preparation of a broad scope of the corresponding reduced derivatives in up to 90% yield. The protocol has a simple and safe experimental setup, in which water was employed as the hydrogen source. To further demonstrate the synthetic utility of this transformation, the antidiabetic API Pioglitazone was prepared in 81% yield. To the best of our knowledge, this is the first hydride and transition-metal free protocol for the synthesis of Pioglitazone, highlighting its potential utility as a greener alternative in both academic and industrial synthesis.

A concise synthesis of molnupiravir in a one-pot two-step approach starting from uridine is described. Formally, herein, two sets of one-pot two-reaction steps introducing simplicity for purifications and using chemically available reagents are presented. In this context, molnupiravir was obtained in up to 68% overall yield and multigram-scale. In addition, HPLC analysis showed the molnupiravir purity above 99%., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The efficient C-4 selective modification of pyridines is a major challenge for the synthetic community. Current strategies are plagued with at least one drawback regarding functional group-tolerant electronic activation of the heteroarene, mild generation of the required alkyl radicals, regioselectivity, safety and/or scalability. Herein, we describe a fast, safe and scalable flow process which allows preparation of said C-4 alkylated pyridines. The process involves a photochemical hydrogen atom transfer (HAT) event to generate the carbon-centered radicals needed to alkylate the C-2 blocked pyridine. In a two-step streamlined flow process, this light-mediated alkylation step is combined with a nearly instantaneous inline removal of the blocking group. Notably, cheap benzophenone plays a dual role in the pyridine alkylation mechanism by activating the hydrocarbon feedstock reagents via a HAT mechanism, and by acting as a benign, terminal oxidant. The key role of benzophenone in the operative reaction mechanism has also been revealed through a combination of experimental and computational studies., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We report the synthesis and characterization of two novel tetra-cationic porphyrins, containing Pt(II) or Pd(II) polypyridyl complexes attached at the peripheral position of N 4 -macrocycle. Compounds were characterized through elemental analysis, molar conductivity, cyclic voltammetry, and spectroscopy analysis. Photophysical and photobiological parameters were also evaluated. Also, the binding capacity of each porphyrin with human serum albumin (HSA) was determined by UV-Vis, steady-state, and time-resolved fluorescence spectroscopy, combined with molecular docking calculations. The results suggest that the interaction of these compounds is spontaneous, weak to moderate, and probably occurs at site III (subdomain IB) by non-covalent forces, including van der Waals and H-bonding. Moreover, porphyrins containing peripheral complexes improve their interactions with biomolecules, show good photostability, generate reactive oxygen species under white light studied by electron paramagnetic resonance (EPR) analysis, and promote photo-damage of HSA.

Numerous methodologies to obtain pyridines from ylidenemalononitriles are described in the literature. Nevertheless, they are limited to the use of microwave or conventional heat and few lead to 2,3,4 or 2,3,4,5-substituted pyridines as multi-proposal molecular scaffolds or even universal pyridines. Herein, we present a mild and facile solvent-free methodology to obtain a scope of multi-substituted pyridines at room temperature. We also report an example where one of the resulting amino-nicotinonitriles exhibits a preliminary evidence of aggregation-induced emission (AIE).

In the present study, the photophysical properties and preliminary time-dependent density functional theory (TD-DFT) data of new rhenium(i) polypyridyl compounds, fac-[Re(L)(Am2phen)(CO)3]0/+, where Am2phen = 4,7-diamine-1,10-phenanthroline and L = Cl and ethyl isonicotinate (et-isonic), provided new insights into excited-state deactivation through an unusual inversion between two metal-to-ligand charge-transfer excited states. In addition, their cellular uptake using breast cancer (MCF-7) and melanoma (SkMel-147 and SkMel-29) cell lines and bioactivity were investigated and their cell-killing mechanism and protein expression were also studied. Preliminary TD-DFT results showed that both compounds exhibited a strong and broad absorption band around 300-400 nm which corresponds to a combination of ILAm2phen and MLCTRe→Am2phen transitions, and a strong contribution of charge transfer transition MLCTRe→et-isonic for fac-[Re(et-isonic)(Am2phen)(CO)3]+ is also observed. In contrast to typical Re(i) polypyridyl complexes, the substitution of Cl with the et-isonic ligand showed a bathochromic shift of the emission maxima, relatively low emission quantum yield and fast lifetime. Photophysical investigation of the fac-[ReCl(et-isonic)2(CO)3] compound provided meaningful information on the excited state manifold of the fac-[Re(L)(Am2phen)(CO)3]0/+ complexes. As shown in the absorption profile, a remarkable inversion of the lowest-lying excited state takes place from the usually observed MLCTRe→Am2phen to the unusual MLCTRe→et-isonic. The lipophilicity of the positive-complex was higher than that of the non-charge compound and the same trend for the activity against cells was observed, in the absence of light. In addition, flow cytometry and Western Blot analyses showed an overexpression of pro-caspase-9, suggesting a caspase proteolytic cascade through an intrinsic-pathway apoptosis mechanism. The photophysical properties of these compounds reported herein provide new fundamental insights into the understanding of substituent groups on polypyridyl ligands which are relevant to practical development.

In this study, direct C-H photoarylation of pyrazine with aryldiazonium salts under visible-light irradiation (blue-LEDs) is described, and additional examples including photoarylations of pyrimidine and pyridazine are also covered. The corresponding aryl-diazines were prepared in yields up to 84% only by mixing and irradiating the reaction with no need for an additional photocatalyst. We demonstrate the efficacy of this protocol by the scope with electron-donor, -neutral, and -withdrawing groups attached at the ortho , meta , and para positions of the aryldiazonium salts; the results are better than those reported for ruthenium-complex mediated photoarylations. Additionally, we demonstrate the robustness of this methodology with a 5 mmol scaled-up experiment. Mechanistic studies were carried out giving support to the proposal of a photocatalyzed approach by an electron donor-acceptor (EDA) complex, also highlighting the crucial role that solvents play in the formation of the EDA complex., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

1H and 13C NMR spectroscopy is used to investigate the organic constituents of metal complexes, MOFs and coordination compounds synthesised under solvothermal and precipitation conditions. The elucidation of the ligands in paramagnetic compounds bearing Cu2+ (d9), Gd3+ (f7), Eu3+ (f6), Fe3+ (d5), ions after treatment with a cationic exchange resin is possible. We prove the efficiency of two post-synthesis linker modifications on diamagnetic IRMOF-3 Zn2+ (d10) with ethyl isocyanate and benzyl bromide.

In the present work, new rhenium(i) polypyridyl compounds, fac-[Re(L)(CO)3(cbz2phen)](+/0) where cbz2phen = 4,7-di(9H-carbazol-9-yl)-1,10-phenanthroline and L = Cl(-), pyridine (py) or 2-aminomethylpyridine (ampy) were synthesized and characterized by (1)H NMR, UV-Vis and IR spectroscopy combined with theoretical calculations using time-dependent density functional theory (TD-DFT). Their photophysical properties were investigated by steady state and time-resolved emission spectroscopy. These compounds show a strong and broad absorption band around 350-500 nm that, also by TD-DFT, corresponds to the carbazol → phenanthroline intraligand charge transfer transition, (1)ILCTcbz2phen, with some contribution of the Re(i) → phenanthroline metal-to-ligand charge transfer transition, (1)MLCTRe→cbz2phen. In contrast to typical Re(i) polypyridyl complexes, cbz2phen-based Re(i) compounds exhibit two emission maxima in CH3CN solution and relatively low emission quantum yields, 10(-3)-10(-2). Solution phase time-resolved photoluminescence and excited state quenching experiments provided meaningful information on the presence of multiple emitter states after light excitation, which were identified as an (1)ILCTcbz2phen excited state deactivation at higher energies and a long-lived phosphorescence attributed to the (3)MLCTRe→cbz2phen excited state. When embedded into a PMMA matrix, the radiative decay from the singlet state is inhibited and the contribution of both (3)MLCT and (3)ILCTcbz2phen to the luminescence is observed. The photophysics of these Re(i) compounds reported herein provide new insights into the understanding of substitutional groups on the polypyridyl ligands that are relevant to practical and fundamental development of photo-induced molecular devices.

The synthesis of a new tetrabromobacteriochlorin BCBr4 is reported having the 3,4-dibromo-1H-pyrrole-2-carbaldehyde (10) as the major precursor. The BCBr4 was successfully employed in Pd cross-coupling reactions with methyl acrylate, phenyl acetylene and 4-ethynylanisole. In all three cases, the desired tetra-coupled products were obtained in good to excellent yields, and present a significant red shift in the UV-Vis bands above 800 nm. DFT and TD-DFT theoretical analyses of the NIR bacteriochlorin chromophores were performed in order to evaluate the effect of β substitution on their electronic structures.

A route to enantiopure (R)-(+)-3-methyl-6-isopropenyl-cyclohept-3-enone-1, an intermediate for terpenoids, has been developed and includes a highly chemo- and regioselective Tiffeneau-Demjanov reaction. Starting from readily available (R)-(-)-carvone, this robust sequence is available on a deca-gram scale and uses flow chemistry for the initial epoxidation reaction. The stereochemistry of the addition of two nucleophiles to the carbonyl group of (R)-(-)-carvone has been determined by X-ray diffraction studies and chemical correlation.