Luminescent PtII and PtIV Platinacycles with Anticancer Activity Against Multiplatinum-Resistant Metastatic CRC and CRPC Cell Models

Platinum-based chemotherapy persists to be the only effective therapeutic option against a wide variety of tumours. Nevertheless, the acquisition of platinum resistance is utterly common, ultimately cornering conventional platinum drugs to only palliative in many patients. Thus, encountering alternatives that are both effective and non-cross-resistant is urgent. In this work, we report the synthesis, reduction studies, and luminescent properties of a series of cyclometallated (C,N,N′)Pt^IV compounds derived from amine–imine ligands, and their remarkable efficacy at the high nanomolar range and complete lack of cross-resistance, as an intrinsic property of the platinacycle, against multiplatinum-resistant colorectal cancer (CRC) and castration-resistant prostate cancer (CRPC) metastatic cell lines generated for this work. We have also determined that the compounds are effective and selective for a broader cancer panel, including breast and lung cancer. Additionally, selected compounds have been further evaluated, finding a shift in their antiproliferative mechanism towards more cytotoxic and less cytostatic than cisplatin against cancer cells, being also able to oxidize cysteine residues and inhibit topoisomerase II, thereby holding great promise as future improved alternatives to conventional platinum drugs.     

Fine Tuning of Heme Reactivity: Hydrogen-Bonding and Dipole Interactions Affecting Ligand Binding to Hemoproteins

Heme reactivity in hemoproteins is governed by the microenvironment near the ligand binding site. In order to quantify polarity effects on heme ligand binding, the kinetics of O₂ and CO binding have been measured for a series of synthetic heme models equipped with a range of groups of varying dipole moments positioned near the heme coordination site. For hemes with polar aprotic groups, both O₂ on (k′) and off rates (k) are found to be dependent on the dipole moment. For model systems containing protic groups, the O₂ off rate is substantially reduced due to hydrogen bonding with the coordinated O₂. The hydrogen-bonding stabilization is estimated to be 0.7 and 1.6 kcal/mol for an alcohol and a secondary amide, respectively. CO binding displays little correlation with a polarity effect; instead it seems to depend upon the size and position of the polar group.     

Dipyrrinone imines: controlling self-association

We report the synthesis of three new dipyrrinone imine analogues and the characterisation of their self-association properties. Based on vapour pressure osmometry and nuclear magnetic resonance studies, placing the imine functional group at C(9) of the dipyrrinone disrupts the native self-association of the dipyrrinone core in a manner that correlates with the conformational A-value of the imine N-substituent.     

Synthesis,characterization and metal ion complexation and extraction capabilities of calix[4]arene Schiff base compounds

The syntheses, characterization and metal ion complexation and extraction capabilities of six new calix[4]arene Schiff base compounds, 5–10, are reported. The preparation of the compounds was achieved by the condensation of 5,17-diamino-11,23-di-tert-butyl-25,27-di-n-butoxy-26,28-dihydroxycalix[4]arene with the appropriate aldehyde (5-bromosalicylaldehyde for 5, 4-anisaldehyde for 6, 4-(dimethylamino)benzaldehyde for 7, 9-anthracenecarboxaldehyde for 8, 1-pyrenecarboxaldehyde for 9, and 9-fluorenecarboxaldehyde for 10) in refluxing ethanol. The compounds were characterized by ¹H and ¹³C NMR spectroscopy, IR spectroscopy, high-resolution mass spectrometry and elemental analysis. The X-ray crystal structures of 7, 8 and 9 (as dichloromethane solvates) revealed that the calixarene molecules adopt H-bond stabilized, distorted-cone conformations and form centrosymmetric dimers in the solid state. Compounds 5–10 did not form host–guest complexes with NEt₄[(bdt)MoO₂(OSiPh₃)] (bdt^2–=benzene-1,2-dithiolate), a potential precursor for biologically relevant oxosulfido-Mo(VI/V) enzyme models; such host–guest complexes have the potential to stabilize these sought-after but highly reactive model compounds. In addition, the capabilities of 5–10 to extract selected metal ions (Ni²⁺, Co²⁺, Cu²⁺, Zn²⁺, Ag⁺, Pb²⁺, Cd²⁺ and Hg²⁺) from an aqueous into an organic phase have been assessed by picrate extraction experiments. Compound 5 displayed exceptional selectivity towards Ni²⁺, compound 7 exhibited enhanced extraction towards all of the metal ions tested and compounds 6, 9 and 10 showed very high selectivity towards Hg²⁺. On the other hand, compound 8 exhibited negligible capacity to extract any of the metal ions tested.     

Synthesis of Sialyl Lewis X Analogues

Abstract

Sialyl Lewis X (SLe^x) analogs 2a and 2b were synthesised, where the N-acetyl-D-glucose and the D-galactose units of SLe^x 1 were replaced with an alkyl and a heteroalkyl spacer. Sulphate ester 6i was also synthesised from alcohol 6b and chlorosulphonic acid. A novel promoter, silver mercaptoethanesulphonate, was used to synthesise α-sialosides 2c. 7b and 7c.     

Synergistic effect of nanoionic destabilization and partial dehydrogenation for enhanced ionic conductivity in MBH4-C60 (M = Li+, Na+) nanocomposites

Journal of Solid State Electrochemistry - In this work, we evaluate the electrochemical properties of MBH4-C60 (M = Li+, Na+) nanocomposites for potential use as a solid-state electrolyte in...     

Controlling speckle using lenses and free space

The correlation properties of speckle fields are studied for general paraxial systems. The previous studies on lateral and longitudinal speckle size for the case of free-space propagation (Fresnel transform) are generalized to the case of the linear canonical transform. These results have implications for the control of speckle size, through appropriate design of optical systems, with particular relevance for speckle interferometry.     

A Close-to-Aromatize Approach for the Late-Stage Functionalization through Ring Closing Metathesis

An efficient approach for the synthesis of monosubstituted aromatic compounds relying on a ring-closing metathesis followed by spontaneous 1,2-elimination is presented. The efficiency for late-stage functionalization is highlighted in various solvents (up to 920 TON). This approach is compatible with strained cycles and other multiple bonds in the substrate.     

Solar Hydrogen from an Aqueous,Noble‐Metal‐Free Hybrid System in a Continuous‐Flow Sampling Reaction System

We introduce the visible‐light photocatalytic H₂ evolution reaction as catalyzed by a cobaloxime/carbon nitride (C₃N₄) noble‐metal‐free hybrid photosystem by using a continuous‐flow sampling reaction system. The photocatalytic H₂ evolution rate is highly dependent on the structure of C₃N₄, in which porous C₃N₄ shows the best activity compared with bulk C₃N₄ (lamellar) and C₃N₄ nanosheets. When using porous C₃N₄, the system is neither affected by the solution pH, nor the C₃N₄ concentration, nor the structure of the cobaloxime complex.