Electron-donating Research Articles

N-Boron-pyrrole: A negative charge stabilizing group

We show that the N-boron-pyrrole (B-pyrrole) group stabilizes the negatively charged compounds, despite not being an electron withdrawing group (EWG). Density functional theory (DFT) calculations revealed that this distinctive property of the B-pyrrole group arises from enhanced π-electron delocalization within the pyrrole ring. The effect of B-pyrrole group on the Brønsted and Lewis acidity of various compound classes was examined and compared with common EWGs including F, Cl, Br, CN, NO2. Substitution of pyrrole into the boracyclohexadiene derivatives enhances their acidity by about 1–6 kcal mol−1 while the acidity enhancement due to pyrrole substitution into boric acid was about 17 kcal mol−1. Interestingly, B(Pyrrole)3 exhibited a fluoride affinity comparable to BF3 (∼78 kcal mol−1) and approximately 15 kcal mol−1 higher than that of BH3.

SAR Study on Thiolato-Bridged Triosmium Carbonyl Clusters: Higher Reactivity Does Not Equal Higher Antiproliferative Activity.

A structure-activity relationship study on triosmium clusters of the general formula Os3(μ-H)(μ-SC6H4X)(CO)10 (2-X, where X = o-, m- or p-NH2; o-, m- or p- OH; p-H, -Br, -NO2, -COOH or -CH2COOH) show that their antiproliferative activity is through the cluster core, and the nature and position of the phenyl ring substituent X shows a significant impact on the activity. Clusters with an electron-withdrawing group are more reactive but are thus quickly consumed through reaction with serum, while those with an electron-donating group persists sufficiently to enter the cells and result in higher antiproliferative activity. Interestingly, m-substituted clusters and those with lipophilicity >6.0 also exhibit higher antiproliferative activity. In contrast, o-substituted clusters capable of intramolecular hydrogen bonding have lower cytotoxicity. The cluster 2-m-OH, with higher antiproliferative activity and lower reactivity with serum, is a potential lead compound for further mode of action studies.

Convergent Paired Electrosynthesis of β-Nitroalcohols Using an Electrogenerated Base

Organic electrosynthesis has attracted much attention as an environmentally benign organic synthesis process, because it is a redox process that does not use oxidizing or reducing agents. In organic electrosynthesis, only one of the reactions, oxidation at the anode or reduction at the cathode, is often targeted, and the counter electrode is mostly used only to conduct electric current. In contrast, paired electrosynthesis targets both anodic and cathodic reactions and is attractive from the viewpoint of current efficiency. Furthermore, convergent paired electrosynthesis, which yields a single product by the reaction between active species generated at the anode and cathode, is ideal in terms of product separation. On the other hand, β-nitroalcohols are useful organic synthetic intermediates and synthesized by the Henry reaction of carbonyl compounds with nitroalkanes. With these facts in mind, a convergent paired electrosynthesis of β-nitroalcohols was designed by combining anodic generation of benzaldehydes from benzyl alcohols and cathodic formation of nitromethyl anion from nitromethane (CH3NO2) via an electrogenerated base (EGB).The first step was to examine the electrolysis conditions for paired electrolysis of benzyl alcohol (1) using an undivided cell. The paired electrolysis of 1 was performed using Bu4PBF4 or Bu4NBF4 as the supporting electrolyte and CH3NO2 as the solvent. As a result, the yield of β-nitroalcohol (3) with the use of Bu4PBF4 was 48%, which was about twice that with the use of Bu4NBF4.In the paired electrolysis, there are three possible probases (PBs) such as Bu4N+, Bu4P+, and CH3NO2. To verify the PB, linear sweep voltammetry of Bu4NBF4 and Bu4PBF4 was demonstrated in CH3NO2, respectively. Furthermore, linear sweep voltammetry of Bu4NBF4, Bu4PBF4 and CH3NO2 was also demonstrated in CH3CN, respectively. These results suggested that CH3NO2 as the solvent, rather than Bu4NBF4 and Bu4PBF4, is mainly reduced at the cathode. To further validate the EGB that occurs in the reaction system, the electrolysis in 0.1 M Bu4PBF4/CH3NO2 was carried out in the absence of 1 using a divided cell. After the electrolysis, CH3NHOH was detected by TLC and 1H NMR in the cathode chamber. This indicates that CH3NHOH or its precursor derived from CH3NO2 may act as an EGB in this reaction system.Finally, the paired electrosynthesis of various β-nitroalcohols was carried out using benzyl alcohols having an electron-withdrawing group on the benzene ring. As a result, the corresponding β-nitroalcohols were formed in moderate yields with the exception of p-nitrobenzyl alcohol.In conclusion, we have successfully demonstrated the paired electrosynthesis of β-nitroalcohols combining anodic generation of benzaldehydes and cathodic formation of nitromethyl anion via an EGB using an undivided cell. This paired electrosynthesis can be applied to the synthesis of various β-nitroalcohols and is expected to make a significant contribution to the synthesis of pharmaceuticals and agrochemicals. Figure 1

Electrochemical C–H Arylation of Polythiophenes By Using Aryldiazonium Salts

Electrochemical post-functionalization is a polymer reaction method in which a nucleophile (or electrophile) attacks the doping state of a π-conjugated polymer generated by applying a potential to the polymer film1,2). This reaction scheme faces various challenges, including the limitation that only conducting polymers can be used as a precursor in the solid state. In order to solve this problem, development of a liquid-phase electrochemical post-functionalization is required. However, it is also known that electron transfer between electrodes and dissolved polymers does not proceed efficiently. Therefore, in this study, we developed a liquid-phase electrochemical post-functionalization that does not rely on direct electron transfer between polymers and electrodes. This method is expected to broaden the application of the electrochemical post-functionalization. Based on the report on the electrochemical C–H arylation of heteroaromatic rings by using the aryl radicals produced by the reduction of aryldiazonium salts3), we investigated to apply the reaction for the C–H arylation of poly(3-hexylthiophene) (P3HT). This approach allows for direct C–H bond functionalization without the need for introducing a functional group beforehand. Moreover, the environmentally friendly electric energy is used as the reaction driving force, avoiding need of a metal catalyst required in conventional methods4,5). Constant current electrolysis of P3HT dissolved in chlorobenzene with an aryl diazonium salt was conducted, and the introduction of an aryl group into the 4-position of the thiophene ring was confirmed by 1H NMR. However, the 1H NMR spectrum of the product (P3HT-Ar) suggested that an unsubstituted phenyl group derived from chlorobenzene was also introduced. Subsequent solvent investigation showed that using a mixed solvent (CHCl3/CH2Cl2 = 2:1) suppressed this side reaction. In addition, the formation of aryldiazonium salts in-situ, by adding 4-nitroaniline and tBuONO, yielded products with the higher degree of functionalization compared to the direct addition of aryldiazonium salts. Current density studies showed that at low current density conditions suppressed side reactions and improved the degree of functionalization. Furthermore, the degree of functionalization could be controlled to a certain range from 0% to 30%, by adjusting the charge passed. It was also possible to introduce 4-trifluoromethylphenyl group in this protocol. As a reference condition, when unsubstituted aniline without an electron-withdrawing group was used as a substrate, no arylation reaction proceed. Finally, the photophysical and electrochemical properties of P3HT-Ar were investigated. CV measurements of P3HT and P3HT-Ar with different degree of functionalization showed the oxidation potential shifted positively with increasing the degree of functionalization. The reduction peak, which did not appear in P3HT, was observed for P3HT-Ar. Furthermore, UV-vis absorption spectroscopy revealed that the maximum absorption wavelength (λmax abs) shortened as the degree of functionalization increased. These are possibly induced by the electron-withdrawing property of the 4-nitrophenyl group and the decrease in the effective π-conjugation length due to the main chain twisting. The fluorescence quantum yield significantly decreased with increasing the degree of functionalization, attributed to the fluorescence quenching effect of the 4-nitrophenyl group.Reference1) S. Inagi, T. Fuchigami, Macromol. Rapid Commun., 2014, 35, 854.2) T. Kurioka, S. Inagi, Chem. Rec., 2021, 21, 2107.3) D. Hata, M. Tobisu, T. Amaya, Bull. Chem. Soc. Jpn., 2018, 91, 1749.4) Y. Li, G. Vamvounis, J. Yu, S. Holdcroft, Macromolecules, 2001, 34, 3130.5) H. Goto, B. Ochiai, Y. Matsumura, Electrochemistry, 2023, 91,112004.6) D. Giri, S. N. Islam, S. K. Patra, Polymer, 2018, 134, 242. Figure 1

Influence of Morphology and Surface Chemistry on Ni-Exsolved Perovskite Oxides for Direct Ammonia Solid Oxide Fuel Cells

Ni-YSZ as an anode material for solid oxide fuel cells (SOFCs) has shown excellent catalytic, electrical, and thermal properties. However, when applied to direct ammonia (DA) fed SOFCs, Ni coarsening and microstructural degradation caused by Ni nitrification resulted in a decrease in the electrode reactivity and an increase in contact resistance, thereby reducing the performance of DA-SOFCs. Nano-size metal exsolved perovskite oxides have been intensively investigated as an alternative anode due to superior catalytic activity and anti-coarsening under various fuel conditions. In this study, Ni exsolution behavior, ammonia decomposition, and surface chemistry on Ni substituted (La,Sr)0.8TiO3- δ oxides were analyzed. Then it was applied to the anode of DA-SOFCs to evaluate cell performance and durability. Ni exsoluted oxides were efficient to decompose ammonia at reduced temperatures due to enlarged catalytic sites and electronic donation. The cell using Ni exsoluted perovskite anode indicated a significant improvement of durability for excellent catalyst stability while the cell performance was comparable with that of Ni-YSZ based DA-SOFC.

Stenhouse Salts: Visible Light Photoswitches for Protic Environments.

Designing photoswitches that have large structural changes, are visible-light responsive, and are compatible with water is a major challenge for moving toward applications in biological systems. Despite the potential for Stenhouse salts to be a water-compatible counterpart to the popular DASA photoswitches, there has not yet been any major investigation into their properties as a photoswitch. Here, we report a series of aniline-based Stenhouse salt (AnSten) photoswitches with electron donating and withdrawing groups. AnSten photoswitches reversibly switch from a visible light absorbing isomer to a visible light transparent isomer upon irradiation with green light. The dark equilibrium and switching kinetics are dependent on the electronics of the aniline. These molecules switch reversibly in common protic solvents including water and hydrogels. Stenhouse salts show significant potential as a visible light active, water compatible, negative photochromic, T-type photoswitch with a large structural change.

Microwave-assisted Reduction of Ketones Using Decaborane in Aqueous Solution

The reduction of ketones to secondary alcohols is an essential reaction in organic chemistry, and various reagents are utilized for this purpose. Herein, we have reported the reduction of ketone using decaborane in conventional as well as microwave-assisted methods in aqueous solution. Different types of aromatic ketones containing distinct functional groups were analyzed. We observed that ketones having an electron-withdrawing group showed a faster reaction rate with higher yield as compared to the ketones with electron-donating groups. Additionally, a comparison between microwave- assisted and conventional synthesis was done by evaluating the total reaction time and percentage yield. The results indicate that microwave-assisted syntheses lead to higher yields within very short reaction times.

Synthesis of Pyranocoumarin through MCRs: Modulation of this Approach as a Function of Substituent Effect Forms the Furocoumarin and 4-Hydroxy-3-styryl Coumarin as a Function of Solvent Effect.

The synthesis of pyranocoumarin is reported from 4-hydroxycoumarin, styrene oxide, and DMSO in the presence of p-TSA·H2O at 110 °C using a three-component reaction. Interestingly, a CH2 moiety from DMSO gets inserted in this reaction to form the pyranocoumarin ring. The plausible mechanism for this interesting reaction was proposed and validated using quantum chemical methods. Interestingly, when the reactions were performed with 7-methoxy-4-hydroxycoumarin and styrene oxides, having an electron-withdrawing group, the reaction followed a two-component pathway, and furocoumarins were obtained in good yields. Switching the solvent from DMSO to CH3CN for the same reactants results in the exclusive formation of the novel monomeric product 4-hydroxy-3-styryl-2H-chromen-2-one (5) instead of the expected furocoumarins. Interestingly, one of the novel monomeric products, 4-hydroxy-3-styryl-2H-chromen-2-one, directly undergoes unexpected cyclization to provide a more interesting and complex tricyclic product. The salient features of the present strategy are its easy handling, commercial availability of starting material, metal-free synthesis, inexpensive catalysts, environmentally benign, and high atom economy.

The Dual-Role of Benzothiadiazole Fluorophores for Enabling Electrofluorochromic and Electrochromic Devices.

Three unsymmetric fluorophores differing in their flanking electron acceptor (-NO2, -CN, -CHO) were investigated for their electrofluorochromism and electrochromism. The emission yield of the -NO2 substituted fluorophore in the solid state was ca. 9-fold less than its -CN and -CHO counterparts. Visible color changes of the fluorophores were observed with an applied potential. The intensity of the near-infrared absorption at ca. 1500 nm formed upon electrochemical oxidation was contingent on the electron-withdrawing group: 2-fold more intense with the -CN substitution than its -H counterpart. The coloration efficiency was upwards of 655 cm2 C-1 and the bleaching kinetics (tb; 22 s) of the NIR band decreased according to -NO2 > -CN > - CHO ≈ -H. The electrochemically generated states could be reversibly formed during 120 min of switching the applied potential. The contrast ratio of the radical cation and the NIR absorption was near unity and 60-82%, respectively. The photoemission intensity of the fluorophores could also be modulated with applied potentials. The collective electrochemically mediated color switching and emission intensity modulation along with their solid-state emission demonstrate that benzothiadiazole fluorophores can play a dual role in chromic devices both as the color switching and photoemission intensity modulating material.

Stabilized Ag nanoparticles loaded smart poly(chitosan-N-isopropylacrylamide-methacrylic acid) hybrid microgels for catalytic reduction of nitroarenes

Nitroarenes (NAs) are one of the most toxic pollutants in the water which cannot easily be eliminated. This challenge can be resolved with conversion of NAs into less toxic aryl amines (AAs) rapidly in the presence of a suitable catalyst. Therefore, poly(chitosan-N-isopropylacrylamide-methacrylic acid) P(ChS-NIPAM-MAA) P(ChNM) microgels were synthesized by microwave irradiations which were then fabricated with silver (Ag) nanoparticles (NPs) by in-situ reduction method and characterized with TEM, XRD, DLS, FTIR, and SEM techniques. The Ag-P(ChNM) hybrid microgels showed pH and temperature responsive behavior along with long time stability. The catalytic efficiency of Ag-P(ChNM) was evaluated for the reduction of 4-nitroaniline (4NiA) under different conditions such as concentration of NaBH4, temperature, content of Ag-P(ChNM), and 4NiA concentration. The Ag-P(ChNM) successfully converted different NAs into their corresponding AAs catalytically with high yields. The highest yield was obtained for 4-nitrophenol (4NiP) (99%) and the lowest for 2,4-dinitrophenylhydrazine (2,4DNiPH) (71%). Electron-withdrawing group containing derivatives of NAs rapidly reduced into AAs than electron-donating substituents. They exhibited excellent catalytic efficiency, stability, recyclability, and maintained their catalytic efficiency over multiple cycles.

Structural optimization of pyridine quinoxaline cobalt (II) catalysts for MMA polymerization based on systematical SCSC transformation study

The Schiff base condensation reaction was adopted to synthesize a series of pyridine-based quinoxaline ligands (L1, L2, L3, L4) using 2-acetylpyridine and 1,2-phenylenediamine aromatic amines with different substituents of –OCH3, –F, -Cl, -Br. Then, four symmetrical dinuclear metal complexes (1–4) were obtained by coordination reaction of the synthesized ligands with CoCl2·6H2O, and six unexpectedly systematic and novel solvent-involved asymmetric mononuclear metal complexes (1A-4A, 3B, 4B) were obtained during single crystals cultivating by solvent diffusion method. The microscopic composition of the complexes were proved by a series of characterizations such as elemental analysis, IR and UV–vis. At the same time, by improving the single crystal culture technology, full crystal sample of compounds was obtained and X-ray single crystal diffraction showed a rare single crystal to single crystal structure transition (SCSC) phenomenon in this study. Furthermore, the catalytic properties of the complexes for MMA polymerization was explored, it was found that the catalytic activity of complexes 1–4 containing different types of substituents on pyridyl quinoxaline ligand was in the order of 1 < 2 <3 < 4, indicating that the complex with an electron-withdrawing substituent showed the higher activity than that of electron-donating substituent. Complexes 1A-4A, 3B and 4B showed higher catalytic activity in MMA polymerization than 1–4, which confirmed that the catalytic activity of mononuclear complexes were generally higher than that of binuclear complexes.

Copper(I)-Catalyzed Asymmetric Nucleophilic Addition to Aldehydes with Skipped Enynes.

The development of sustainable and novel strategies for constructing complex chiral molecules with versatile transformation potential is a long-term pursuit in the chemistry community. We report a copper(I)-catalyzed enyne addition to aldehydes under proton-transfer conditions, unlike previous examples which were limited to the use of preformed reactive nucleophiles containing allylic heteroatoms or electron-withdrawing groups. This protocol provides an efficient platform for installing chiral allylic alcohol moieties with a broad substrate scope and high regio-, stereo-, and enantioselectivity.

4-Furanylvinylquinoline derivative as a new scaffold for the design of oxidative stress initiator and glucose transporter inhibitor drugs

In the present study, a detailed analysis of the effect of a substitution at the C4 position of the quinoline ring by styryl or furanylvinyl substituents on the structure-antitumour activity relationship was conducted. After analysing a library of derivatives from the styrylquinoline and furanylvinylquinoline groups, we selected the most active (IC50 below 100 nM) derivative 13, which contained the strongly electron-withdrawing nitro group in the furan substituent. The mechanism of action of this compound was studied on cell lines that differed in their p53 protein status. For this derivative, both cell cycle arrest (in G2/M phase in both HCT 116 cell lines and S phase for U-251 cell line) and the induction of apoptosis (up to 66% for U-251 cell line) were revealed. These studies were then confirmed by other methods at the gene and protein levels. Interestingly, we observed differences in the mechanism of action depending on the presence and mutation of the p53 protein, thus confirming its key role in cellular processes. Incubation with derivative 13 resulted in the induction of oxidative stress and triggered a cascade of cellular defence proteins that failed in the face of such an active compound. In addition, the results showed an inhibition of the GLUT-1 glucose transporter, which is extremely important in the context of anti-cancer activity.

C2-Arylated Indoles and Benzofurans through Formal (4 + 1) Annulation of N-Sulfonyl-2-aminobenzaldehydes and Salicylaldehyde Derivatives with Electron-Deficient Benzyl Chlorides.

A two-step formal (4 + 1) annulation-dehydration reaction offers a convenient route to C2-arylated indoles and benzofurans. This reaction exploits the bifunctional reactivity of electron-deficient benzyl chlorides with N-sulfonyl-2-aminobenzaldehydes or salicylaldehyde derivatives. The reaction tolerates both electron-withdrawing and donating groups on the substituted aldehydes, as well as variation of electron-withdrawing groups at the para position of the benzyl chloride reagent. This work also identifies interesting byproducts resulting from the self-reaction of these benzyl chlorides under basic conditions.

Synthesis and Functionalization of Sulfoximine‐Bicyclo[1.1.0]butanes: Functionalizable, Tuneable and Cysteine‐Selective Chiral Warheads

Electrophilic covalent warheads with appropriate reactivity and selectivity are crucial to the investigation of protein function and the discovery of therapeutics. Here we report the synthesis of sulfoximine bicyclo[1.1.0]butanes (BCBs) as novel thiol reactive chiral warheads, achieved in one‐pot from methylsulfoximines. Unusually the warhead can then be derivatized, keeping the BCB intact, over 3 vectors: i) sulfoximine N‐modification instills a broad range of strain‐release reactivity; ii) sp2‐cross‐coupling reactions on aryl‐BCB‐sulfoximines allows direct diversification, and iii) functionalization of the BCB motif itself is achieved by metalation and trapping with electrophiles. The BCB sulfoximines are shown to react selectively with cysteine including in a protein model (CDK2) under biocompatible conditions. Preliminary data indicate suitability for chemoproteomic applications, and enantioselective cysteine‐labelling. The reactivity of sulfoximine BCBs with electron withdrawing groups on nitrogen is comparable to acrylamides with low to moderate reactivity.

Regulating Electric Double Layer via Self-Assembled Monolayer for Stable Solid/Electrolyte Interphase on Mg Metal Anode.

Modulating the cationic solvation structure with high donor-number (DN) additive is an effective strategy to construct a stable solid electrolyte interphase (SEI) on the Mg anode, which necessitates meticulous consideration of electrolyte chemistry and substantial quantities of additives. Notably, the electric double layer (EDL) adjacent to anode is pivotal role in SEI formation yet remains understudied. In this study, we propose a novel self-assembled monolayer (SAM) strategy by utilizing (trifluoromethyl)trimethylsilane (TFTMS, only 2 vol %, 1.4 mol %, 0.135 mol L-1), a low DN but strong Mg metal absorbability through electron-withdrawing groups(-CF3), to modulate the complex structure of the Helmholtz absorption plane. Through dipole-dipole interaction between the electronegative fluorine (-CF3 of TFTMS) and electropositive hydrogen (-CH3/-CH2 of solvents), TFTMS weakens solvent-Mg2+ coordination and thus enhances anion-Mg2+ interaction, inducing a stable and dense SEI with superior electronic insulation to realize horizontal Mg plating/stripping. Consequently, the designed electrolytes enable the symmetric cells to cycle stable for up to 1000 hours and reversible Mg plating/stripping under 5 mA cm-2, they show favorable compatibility with various cathodes. More importantly, the SAM strategy has good generality in other electrolyte systems, demonstrating a simple and effective route to promote the practical application of rechargeable magnesium battery.

Extended π-conjugated N-heteroaromatic molecules for fast-charging and high operating voltage aqueous zinc-ion batteries

Aqueous zinc-ion batteries (AZIBs) with redox-active organic compounds as electrodes attract wide attention due to their structural diversity, sustainability and inherent safety. However, the rational structural design of advanced organic electrodes with high practical capacity, long cycle life and high rate performance is still a great challenge. Herein, a strategy to improve the electrochemical performance of electrodes in AZIBs by constructing an extended π-conjugated hexaazatrinaphthalene (HATN)-based structure with electron-withdrawing cyano groups, 5, 6, 11, 12, 17, 18-hexaazatrinaphthalene-2, 3, 8, 9, 14, 15-hexacarbonitrile (HATN-6CN), is reported. The reduced lowest unoccupied molecular orbital (LUMO) energy level improves the discharge voltage to 0.71 V. Furthermore, HATN-6CN features abundant redox-active sites, solvent resistance and a smaller energy gap, enabling stable and rapid co-storage of H+ and Zn2+. As expected, HATN-6CN electrode achieves a high reversible capacity of 277mAhg−1 at 0.1Ag−1, an excellent rate capability of 94mAhg−1 at 10Ag−1, and a good capacity retention of 65 % after 10,000 cycles at 10 A/g, simultaneously. The ex-situ characterization and theoretical simulation results demonstrate that Zn2+ and H+ cations coordinate synergistically with CN groups and simultaneously reversibly form zinc hydroxide sulfate hydrate. This work affords an appropriate structural design of advanced organic electrodes for AZIBs.

Three-dimensional representation of the pure electric-dipole and the mixed first hyperpolarizabilities: The modified unit sphere representation.

In this work, the theory of the modified unit sphere representation (mUSR) has been proposed as a computational tool suitable for the three-dimensional representation of the pure electric-dipole [ ] as well as of the mixed electric-dipole/magnetic-dipole [ and ] or electric-dipole/electric-quadrupole [ and ] first hyperpolarizabilities. These five quantities are Cartesian tensors and they are responsible for the chiral signal in the chiroptical version of the hyper-Rayleigh scattering (HRS) spectroscopy, namely the HRS optical activity (HRS-OA) spectroscopy. For the first time, for each hyperpolarizability, alongside with the three-dimensional representation of the whole (i.e., reducible) Cartesian tensors, the mUSRs are developed for each of the irreducible Cartesian tensors (ICTs) that constitute them. This scheme has been applied to a series of three (chiral) hexahelicene molecules containing different degrees of electron-withdrawing (quinone) groups and characterized by the same (positive) handedness. For these molecules, the mUSR shows that, upon substitution, the most remarkable qualitative and semi-quantitative (enhancement of the molecular responses) effects are obtained for the pure electric-dipole and for the mixed electric-dipole/magnetic-dipole hyperpolarizabilities.

The impact of 9-azaglycophymine and phenylguanidine derivatives on the proliferation of various breast cancer cell lines in vitro and in vivo

Quinazolinones, particularly 9-azaglycophymines, and closely related derivatives and precursors were tested in vitro against various breast cancer cell lines representing the major types of breast tumors. Among the 49 compounds tested, azaglycophymine derivative 19 with an electron-withdrawing substituent demonstrated the most significant anti-proliferative effects, with IC50 values of around 4 µM. Extensive cell-based investigations revealed that compound 19 induced caspase-dependent apoptosis in HCC1937 (human TNBC), BT-474 (human HER2+/HR+), and 4T1 (mouse TNBC) cells. In contrast, in MDA-MB-468 (human TNBC) and MCF-7 (human HR+) cells, the cell death was induced via a non-apoptotic pathway. The in vivo efficacy of compound 19 was validated using a syngeneic orthotopic 4T1 model in BALB/c mice, resulting in significant reduction of 4T1 breast tumor growth upon intraperitoneal (i.p.) application of doses of 5 or 20 mg/kg. These findings highlight the potential of compound 19 as a promising scaffold for the development of new therapeutic agents for various types of breast cancer and a first structure-activity insight.

Precise Single-Atom Modification of Hybrid Lead Chlorides for Electron Donor-Acceptor Effect and Enhanced Photocatalytic Aerobic Oxidation.

Hybrid lead halides show significant potential in photocatalysis due to their excellent photophysical properties, but the atomically precise modification of their organic component to achieve synergistic interactions with the lead halide units remains a great challenge. Herein, for the first time, we have employed the crystal engineering strategy to construct a class of single-atom-substituted hybrid lead halides with electron donor-acceptor (D-A) effect. The lead halide frameworks consist of 1D linear [PbCl]+ chains as inorganic building units and benzoxadiazole/benzothiadiazole/ benzoselenadiazole-funtionalized dicarboxylates as linkers. The covalent bonding between the organic ligands with electron-withdrawing groups and the electron-rich lead halide units not only facilitate the charge separation, but also enhance structural robustness that is critical for photocatalysis. The D-A structured lead halides serve as highly efficient heterogeneous photooxidation catalysts, including aerobic oxidation of C(sp3)-H bonds, oxidative coupling of primary amines, oxidation of phenylboronic acids and selective oxidation of sulfides that are demonstrated in 30 examples. Importantly, these photooxidation reactions are able to be driven by natural sunlight and ambient air to afford quantitative yields. Moreover, our lead halide photocatalysts are successful to fix into a photocatalytic flow system, which enables the flow-type synthesis of high value-added photooxidation products on a gram scale.