Design, synthesis, molecular modeling, and bioactivity evaluation of 1,10-phenanthroline and prodigiosin (Ps) derivatives and their Copper(I) complexes against mTOR and HDAC enzymes as highly potent and effective new anticancer therapeutic drugs.

Breast cancer is the second type of cancer with a high probability of brain metastasis and has always been one of the main problems of breast cancer research due to the lack of effective treatment methods. Demand for developing an effective drug against breast cancer brain metastasis and finding molecular mechanisms that play a role in effective treatment are gradually increasing. However, there is no effective anticancer therapeutic drug or treatment method specific to breast cancer, in particular, for patients with a high risk of brain metastases. It is known that mTOR and HDAC enzymes play essential roles in the development of breast cancer brain metastasis. Therefore, it is vital to develop some new drugs and conduct studies toward the inhibition of these enzymes that might be a possible solution to treat breast cancer brain metastasis. In this study, a series of 1,10-phenanthroline and Prodigiosin derivatives consisting of their copper(I) complexes have been synthesized and characterized. Their biological activities were tested in vitro on six different cell lines (including the normal cell line). To obtain additional parallel validations of the experimental data, some in silico modeling studies were carried out with mTOR and HDAC1 enzymes, which are very crucial drug targets, to discover novel and potent drugs for breast cancer and related brain metastases disease.

Mechanical-Bond-Induced Exciplex Fluorescence in an Anthracene-Based Homo[2]catenane.

Collisional intermolecular interactions between excited states form short-lived dimers and complexes that lead to the emergence of excimer/exciplex emission of lower energy, a phenomenon which must be differentiated from the photoluminescence (PL) arising from the monomeric molecules. Although the utilization of noncovalent bonding interactions, leading to the generation of excimer/exciplex PL, has been investigated extensively, precise control of the aggregates and their persistence at very low concentrations remains a rare phenomenon. In the search for a fresh approach, we sought to obtain exciplex PL from permanent structures by incorporating anthracene moieties into pyridinium-containing mechanically interlocked molecules. Beyond the optical properties of the anthracene moieties, their π-extended nature enforces [π···π] stacking that can overcome the Coulombic repulsion between the pyridinium units, affording an efficient synthesis of an octacationic homo[2]catenane. Notably, upon increasing the ionic strength by adding tetrabutylammonium hexafluorophosphate, the catenane yield increases significantly as a result of the decrease in Coulombic repulsions between the pyridinium units. Although the ground-state photophysical properties of the free cyclophane and the catenane are similar and show a charge-transfer band at ∼455 nm, their PL characters are distinct, denoting different excited states. The cyclophane emits at ∼562 nm (quantum yield ϕF = 3.6%, emission lifetime τs = 3 ns in MeCN), which is characteristic of a disubstituted anthracene-pyridinium linker. By contrast, the catenane displays an exciplex PL at low concentration (10-8 M) with an emission band centered on 650 nm (ϕF = 0.5%, τs = 14 ns) in MeCN and at 675 nm in aqueous solution. Live-cell imaging performed in MIAPaCa-2 prostate cancer cells confirmed that the catenane exciplex emission can be detected at micromolar concentrations.

A Supramolecular Approach for Modulated Photoprotection, Lysosomal Delivery, and Photodynamic Activity of a Photosensitizer.

Prompted by a knowledge of the photoprotective mechanism operating in photosystem supercomplexes and bacterial antenna complexes by pigment binding proteins, we have appealed to a boxlike synthetic receptor (ExBox·4Cl) that binds a photosensitizer, 5,15-diphenylporphyrin (DPP), to provide photoprotection by regulating light energy. The hydrophilic ExBox4+ renders DPP soluble in water and modulates the phototoxicity of DPP by trapping it in its cavity and releasing it when required. While trapping removes access to the DPP triplet state, a pH-dependent release of diprotonated DPP (DPPH22+) restores the triplet deactivation pathway, thereby activating its ability to generate reactive oxygen species. We have employed the ExBox4+-bound DPP complex (ExBox4+⊃DPP) for the safe delivery of DPP into the lysosomes of cancer cells, imaging the cells by utilizing the fluorescence of the released DPPH22+ and regulating photodynamic therapy to kill cancer cells with high efficiency.

Synthesis of metalated pseudorotaxane polymers with full control over the average linear density of threaded macrocycles.

Here we report the synthesis of metalated main-chain polypseudorotaxanes via ring-opening olefin metathesis copolymerization of macrocycles and metalated [2]catenanes. By varying the feed ratio of the macrocycle and the [2]catenate comonomers, we prepared metalated pseudorotaxane polymers with selected, predictable average linear densities of threaded macrocycles that ranged from 0% to 100%, thus allowing, for the first time, both full and fine control over this key parameter.