Convergent Synthesis of 10 nm Aryleneethynylene Molecular Wires by an Iterative Regioselective Deprotection/Sonogashira Coupling Protocol

The synthesis of a new series of rigid-rod aryleneethynylene derivatives of up to ca. 10 nm molecular length (compounds 16 and 17) is reported using iterative Pd-mediated Sonogashira coupling methodology combined with regioselective removal of the different protecting groups (namely, trimethylsilyl and 2-hydroxyprop-2-yl groups) from the terminal alkyne units. Additionally, the TMS−acetylene unit has been cleanly deprotected to afford a terminal alkyne in the presence of a cyanoethylsulfanyl group. Some of these molecular wires are functionalized with terminal protected thiophenol units for attachment to metal surfaces (compounds 16 and 17). Internal electron-acceptor units have been incorporated into their structures, namely, 9-[di(4-pyridyl)methylene]fluorene (compound 17) or fluorenone (compounds 19−22). Optical absorption and photoluminescence spectra reveal a red shift in the value of λmax with increasing molecular length, which approaches saturation at an effective conjugation length of ca. 15−20 π-units in the molecules, where each phenyl ring or a triple bond is counted as one π-unit

Convergent Synthesis of 10 nm Aryleneethynylene Molecular Wires by an Iterative Regioselective Deprotection/Sonogashira Coupling Protocol

The synthesis of a new series of rigid-rod aryleneethynylene derivatives of up to ca. 10 nm molecular length (compounds 16 and 17) is reported using iterative Pd-mediated Sonogashira coupling methodology combined with regioselective removal of the different protecting groups (namely, trimethylsilyl and 2-hydroxyprop-2-yl groups) from the terminal alkyne units. Additionally, the TMS−acetylene unit has been cleanly deprotected to afford a terminal alkyne in the presence of a cyanoethylsulfanyl group. Some of these molecular wires are functionalized with terminal protected thiophenol units for attachment to metal surfaces (compounds 16 and 17). Internal electron-acceptor units have been incorporated into their structures, namely, 9-[di(4-pyridyl)methylene]fluorene (compound 17) or fluorenone (compounds 19−22). Optical absorption and photoluminescence spectra reveal a red shift in the value of λmax with increasing molecular length, which approaches saturation at an effective conjugation length of ca. 15−20 π-units in the molecules, where each phenyl ring or a triple bond is counted as one π-unit

Are Terminal Aryl Butadiynes Stable? Synthesis and X-ray Crystal Structures of a Series of Aryl- and Heteroaryl-butadiynes (Ar−C⋮C−C⋮C−H)

The synthesis and isolation are reported of a range of terminal aryl- and heteroaryl-butadiynes (ArC⋮C−C⋮CH) 4a−h from 2-methyl-6-(aryl/heteroaryl)hexa-3,5-diyn-2-ol precursors. The stability of 4a−h in solution is concentration dependent:  many of the derivatives can be stored as dilute solutions for several days or even weeks. The X-ray crystal structures have been obtained for five ArC⋮C−C⋮CH derivatives [Ar = 2-(9-fluorenonyl), 4-biphenyl, 2-pyridyl, 4-pyridyl, and 2-pyrazyl]

Are Terminal Aryl Butadiynes Stable? Synthesis and X-ray Crystal Structures of a Series of Aryl- and Heteroaryl-butadiynes (Ar−C⋮C−C⋮C−H)

The synthesis and isolation are reported of a range of terminal aryl- and heteroaryl-butadiynes (ArC⋮C−C⋮CH) 4a−h from 2-methyl-6-(aryl/heteroaryl)hexa-3,5-diyn-2-ol precursors. The stability of 4a−h in solution is concentration dependent:  many of the derivatives can be stored as dilute solutions for several days or even weeks. The X-ray crystal structures have been obtained for five ArC⋮C−C⋮CH derivatives [Ar = 2-(9-fluorenonyl), 4-biphenyl, 2-pyridyl, 4-pyridyl, and 2-pyrazyl]

Nanoscale Aryleneethynylene Molecular Wires with Reversible Fluorenone Electrochemistry for Self-Assembly onto Metal Surfaces

Two rigid-rod conjugated molecules (11 and 12) of ca. 4 and 7 nm length, respectively, bearing protected terminal thiol groups have been synthesized via multistep Sonogashira coupling reactions and shown to possess reversible cathodic solution electrochemistry arising from reduction of the fluorenone units

Nanoscale Aryleneethynylene Molecular Wires with Reversible Fluorenone Electrochemistry for Self-Assembly onto Metal Surfaces

Two rigid-rod conjugated molecules (11 and 12) of ca. 4 and 7 nm length, respectively, bearing protected terminal thiol groups have been synthesized via multistep Sonogashira coupling reactions and shown to possess reversible cathodic solution electrochemistry arising from reduction of the fluorenone units

Synthesis and Crystal Structures of Isolable Terminal Aryl Hexatriyne and Octatetrayne Derivatives: Ar−(CC)_<i>n</i>H (<i>n</i> = 3, 4)

Unprecedented stability has been observed in terminal aryl hexatriyne and terminal aryl octatetrayne derivatives by judicious choice of a bulky, nonplanar headgroup [viz., 4-(3,6-di-tert-butyl-N-carbazolyl)phenyl] which hinders topochemical intermolecular interactions in the crystal lattice

Synthesis and Crystal Structures of Isolable Terminal Aryl Hexatriyne and Octatetrayne Derivatives: Ar−(CC)_<i>n</i>H (<i>n</i> = 3, 4)

Unprecedented stability has been observed in terminal aryl hexatriyne and terminal aryl octatetrayne derivatives by judicious choice of a bulky, nonplanar headgroup [viz., 4-(3,6-di-tert-butyl-N-carbazolyl)phenyl] which hinders topochemical intermolecular interactions in the crystal lattice

Molecular Wires Comprising π-Extended Ethynyl- and Butadiynyl-2,5-Diphenyl-1,3,4-Oxadiazole Derivatives: Synthesis, Redox, Structural, and Optoelectronic Properties

2,5-Diphenyl-1,3,4-oxadiazole (OXD) derivatives with terminal ethynyl- (4a,b) and butadiynyl- (8a,b) substituents have been synthesized in high yields. 2-Methyl-3,5-hexadiyn-2-ol has not been exploited previously in the synthesis of terminal butadiynes. Crystals of 8a and 8b are remarkably stable to long-term storage under ambient conditions. The X-ray crystal structure of 8a reveals that the butadiyne moieties are spatially isolated by the aromatic moieties, which explains the high stability. Two series of derived π-conjugated molecules, Donor−(C⋮C)n−OXD (n = 1, 2) and OXD−(C⋮C)n−Donor−(C⋮C)n−OXD (n = 1) [Donor = tetrathiafulvalene (TTF), bithiophene, 9-(4,5-dimethyl-1,3-dithiol-2-ylidene)fluorene, and triphenylamine], have been synthesized using Sonogashira reactions and characterized by X-ray crystallography, cyclic voltammetry, and optical absorption/emission spectroscopy. The electron-withdrawing effect of the OXD units is manifested by a positive shift of the donor oxidation waves in these systems:  the butadiynylene spacer (n = 2) further shifts the first oxidation waves by 40−80 mV compared to analogues n = 1. The absorption spectra of TTF−OXD hybrids 10d and 11 are blue-shifted by 80 nm compared to the bithienyl-bridged derivative 10f and are similar to the butadiynyl−OXD building-block 8a, demonstrating that conjugation is disrupted by a neutral TTF unit. Solutions of the TTF−OXD and 9-(4,5-dimethyl-1,3-dithiol-2-ylidene)fluorene−OXD hybrids, 10d, 10g, 11, and 13, are only very weakly fluorescent due to quenching from the electron-donor moieties. In contrast, the triphenylamine−OXD hybrids 12a, 12b, 14a, and 14b are fluorescent; the PLQYs of the butadiynylene derivatives 14a and 14b are lower than those of the ethynylene-bridged analogues 12a and 12b

MicroRNA-1287-5p promotes ferroptosis of osteosarcoma cells through inhibiting GPX4

Osteosarcoma is the most prevalent primary bone malignancy in adolescents, and ferroptosis is implicated in its pathogenesis. MicroRNA (miR)-1287-5p plays critical roles in multiple human cancers, and the present study aims to investigate the role and underlying mechanisms of miR-1287-5p in regulating ferroptosis and osteosarcoma progression. Human osteosarcoma cell lines were treated with the mimic, inhibitor or matched controls of miR-1287-5p. Cell viability, colony formation, cell death ratio and ferroptosis were determined. miR-1287-5p expression was downregulated in human osteosarcoma, but upregulated upon ferroptotic stimulation. Overexpression of miR-1287-5p significantly induced, while inhibition of miR-1287-5p suppressed ferroptosis of osteosarcoma cells, thereby modulating cell viability and colony formation. Mechanistic studies indicated that miR-1287-5p directly bound to the 3′-untranslated region of glutathione peroxidase 4 (GPX4) to inhibit its protein level and activity, and that GPX4 overexpression completely abolished the miR-1287-5p mimic-mediated ferroptotic induction and tumor suppression. Moreover, the miR-1287-5p mimic dramatically sensitized human osteosarcoma cells to cisplatin chemotherapy. Our findings prove that miR-1287-5p promotes ferroptosis of osteosarcoma cells through inhibiting GPX4, identifying an adjuvant and even alternative method for the treatment of human osteosarcoma.</p