Metabolic reprogramming is a key cancer hallmark that has led to the therapeutic targeting of glycolysis. However, agents that target dysfunctional mitochondrial respiration for targeted therapy remains underexplored. We report the synthesis and characterization of ten (10) novel, highly potent organometallic gold(iii) complexes supported by dithiocarbamate ligands as selective inhibitors of mitochondrial respiration. The structure of dithiocarbamates employed dictates the biological stability and cellular cytotoxicity. Most of the compounds exhibit 50% inhibitory concentration (IC50) in the low-micromolar (0.50-2.9 μM) range when tested in a panel of aggressive cancer types with significant selectivity for cancer cells over normal cells. Consequently, there is great interest in the mechanism of action of gold chemotherapeutics, particularly, considering that DNA is not the major target of most gold complexes. We investigate the mechanism of action of representative complexes, 1a and 2a in the recalcitrant triple negative breast cancer (TNBC) cell line, MDA-MB-231. Whole-cell transcriptomics sequencing revealed genes related to three major pathways, namely cell cycle, organelle fission, and oxidative phosphorylation. 2a irreversibly and rapidly inhibits maximal respiration in TNBC with no effect on normal epithelial cells, implicating mitochondrial OXPHOS as a potential target. Furthermore, the modulation of cyclin dependent kinases and G1 cell cycle arrest induced by these compounds is promising for the treatment of cancer. This work contributes to the need for mitochondrial respiration modulators in biomedical research and outlines a systematic approach to study the mechanism of action of metal-based agents.The selective cross-coupling of activated electrophiles with unactivated ones has been regarded as a challenging task in cross-electrophile couplings. Herein we describe a migratory cross-coupling strategy, which can overcome this obstacle to access the desired cross-coupling products. Accordingly, a selective migratory cross-coupling of two alkyl electrophiles has been accomplished by nickel catalysis. Remarkably, this alkyl-alkyl cross-coupling reaction provides a platform to prepare 2°-2° carbon-carbon bonds from 1° and 2° carbon coupling partners. PLX4032 concentration Preliminary mechanistic studies suggest that chain-walking occurs at both alkyl halides in this reaction, thus a catalytic cycle with the key step involving two alkylnickel(ii) species is proposed for this transformation.Discrete (M3L2) n cages assembled from a tripodal ligand (L) and metal ions (M Cu(i) or Ag(i)) are embedded in networked coordination hosts formed by partial dissociation of the same discrete cages during the crystallization process. The resulting “eggs-in-an-egg-carton” structures provide unique examples of the co-crystallization of discrete and infinite coordination frameworks.The mechanical strength of individual polymer chains is believed to underlie a number of performance metrics in bulk materials, including adhesion and fracture toughness. Methods by which the intrinsic molecular strength of the constituents of a given polymeric material might be switched are therefore potentially useful both for applications in which triggered property changes are desirable, and as tests of molecular theories for bulk behaviors. Here we report that the sequential oxidation of sulfide containing polyesters (PE-S) to the corresponding sulfoxide (PE-SO) and then sulfone (PE-SO2) first weakens (sulfoxide), and then enhances (sulfone), the effective mechanical integrity of the polymer backbone; PE-S ∼ PE-SO2 > PE-SO. The relative mechanical strength as a function of oxidation state is revealed through the use of gem-dichlorocyclopropane nonscissile mechanophores as an internal standard, and the observed order agrees well with the reported bond dissociation energies of C-S bonds in each species and with the results of CoGEF modeling.Control over the photochemical outcome of photochromic molecules in solution represents a major challenge, as photoexcitation often leads to multiple competing photochemical and/or supramolecular pathways resulting in complex product mixtures. Herein, we demonstrate precise and efficient control over the photochemical behaviour of cyanostilbenes in solution using a straightforward solvent-controlled approach based on supramolecular polymerization. To this end, we designed a π-extended cyanostilbene bolaamphiphile that exhibits tuneable solvent-dependent photochemical behaviour. Photoirradiation of the system in a monomeric state (in organic solvents) exclusively leads to a highly reversible and efficient E/Z photoisomerization, whereas a nearly quantitative [2 + 2] photocycloaddition into a single cyclobutane (anti head-to-tail) occurs in aqueous solutions. These results can be rationalized by a highly regular and preorganized antiparallel J-type arrangement of the cyanostilbene units that is driven by aqueous supramolecular polymerization. The presented concept demonstrates a novel approach towards solvent-selective and environmentally friendly photochemical transformations, which is expected to broaden the scope of supramolecular polymerization.The fragment-centric design promises a means to develop complex xenobiotic protein surface mimetics, but it is challenging to find locally biomimetic structures. To address this issue, foldameric local surface mimetic (LSM) libraries were constructed. Protein affinity patterns, ligand promiscuity and protein druggability were evaluated using pull-down data for targets with various interaction tendencies and levels of homology. LSM probes based on H14 helices exhibited sufficient binding affinities for the detection of both orthosteric and non-orthosteric spots, and overall binding tendencies correlated with the magnitude of the target interactome. Binding was driven by two proteinogenic side chains and LSM probes could distinguish structurally similar proteins with different functions, indicating limited promiscuity. Binding patterns displayed similar side chain enrichment values to those for native protein-protein interfaces implying locally biomimetic behavior. These analyses suggest that in a fragment-centric approach foldameric LSMs can serve as useful probes and building blocks for undruggable protein interfaces.