14 research outputs found
Perovskite Solar Cells Based on Oligotriarylamine Hexaarylbenzene as Hole-Transporting Materials
A cobalt-catalyzed cyclotrimerization of bis(aryl)alkyne is used as an innovative tool to obtain hole-transport materials (HTMs). The novel HTM containing six units of oligotriarylamine (HAB1), characterized by UV-vis, cyclic voltammetry, DFT, and thermogravimetric analysis, confirms its suitability as an efficient HTM in PSCs. A PCE of 17.5% was obtained in HAB1-containing PSCs, a performance comparable to that obtained with spiro-OMeTAD and with slightly better thermal stability
Steric Effects on the Primary Isotope Dependence of Secondary Kinetic Isotope Effects in Hydride Transfer Reactions in Solution: Caused by the Isotopically Different Tunneling Ready State Conformations?
The
observed 1° isotope effect on 2° KIEs in H-transfer
reactions has recently been explained on the basis of a H-tunneling
mechanism that uses the concept that the tunneling of a heavier isotope
requires a shorter donor–acceptor distance (DAD) than that
of a lighter isotope. The shorter DAD in D-tunneling, as compared
to H-tunneling, could bring about significant spatial crowding effect
that stiffens the 2° H/D vibrations, thus decreasing the 2°
KIE. This leads to a new physical organic research direction that
examines how structure affects the 1° isotope dependence of 2°
KIEs and how this dependence provides information about the structure
of the tunneling ready states (TRSs). The hypothesis is that H- and
D-tunneling have TRS structures which have different DADs, and pronounced
1° isotope effect on 2° KIEs should be observed in tunneling
systems that are sterically hindered. This paper investigates the
hypothesis by determining the 1° isotope effect on α- and
β-2° KIEs for hydride transfer reactions from various hydride
donors to different carbocationic hydride acceptors in solution. The
systems were designed to include the interactions of the steric groups
and the targeted 2° H/D’s in the TRSs. The results substantiate
our hypothesis, and they are not consistent with the traditional model
of H-tunneling and 1°/2° H coupled motions that has been
widely used to explain the 1° isotope dependence of 2° KIEs
in the enzyme-catalyzed H-transfer reactions. The behaviors of the
1° isotope dependence of 2° KIEs in solution are compared
to those with alcohol dehydrogenases, and sources of the observed
“puzzling” 2° KIE behaviors in these enzymes are
discussed using the concept of the isotopically different TRS conformations
Small molecule nitroalkenes inhibit RAD51-mediated homologous recombination and amplify triple-negative breast cancer cell killing by DNA-directed therapies
Nitro fatty acids (NO2-FAs) are endogenously generated lipid signaling mediators from metabolic and inflammatory reactions between conjugated diene fatty acids and nitric oxide or nitrite-derived reactive species. NO2-FAs undergo reversible Michael addition with hyperreactive protein cysteine thiolates to induce posttranslational protein modifications that can impact protein function. Herein, we report a novel mechanism of action of natural and non-natural nitroalkenes structurally similar to (E) 10-nitro-octadec-9-enoic acid (CP-6), recently de-risked by preclinical Investigational New Drug-enabling studies and Phase 1 and Phase 2 clinical trials and found to induce DNA damage in a TNBC xenograft by inhibiting homologous-recombination (HR)-mediated repair of DNA double-strand breaks (DSB). CP-6 specifically targets Cys319, essential in RAD51-controlled HR-mediated DNA DSB repair in cells. A nitroalkene library screen identified two structurally different nitroalkenes, a non-natural fatty acid [(E) 8-nitro-nonadec-7-enoic acid (CP-8)] and a dicarboxylate ester [dimethyl (E)nitro-oct-4-enedioate (CP-23)] superior to CP-6 in TNBC cells killing, synergism with three different inhibitors of the poly ADP-ribose polymerase (PARP) and Îł-IR. CP-8 and CP-23 effectively inhibited Îł-IR-induced RAD51 foci formation and HR in a GFP-reported assay but did not affect benign human epithelial cells or cell cycle phases. In vivo, CP-8 and CP-23's efficacies diverged as only CP-8 showed promising anticancer activities alone and combined with the PARP inhibitor talazoparib in an HR-proficient TNBC mouse model. As preliminary preclinical toxicology analysis also suggests CP-8 as safe, our data endorse CP-8 as a novel anticancer molecule for treating cancers sensitive to homologous recombination-mediated DNA repair inhibitors