Mithplatins: Mithramycin SA-Pt(II) Complex Conjugates for the Treatment of Platinum-Resistant Ovarian Cancers

DNA coordinating platinum (Pt) containing compounds cisplatin and carboplatin have been used for the treatment of ovarian cancer therapy for four decades. However, recurrent Pt-resistant cancers are a major cause of mortality. To combat Pt-resistant ovarian cancers, we designed and synthesized a conjugate of an anticancer drug mithramycin with a reactive Pt(II) bearing moiety, which we termed mithplatin. The conjugates displayed both the Mg²⁺-dependent noncovalent DNA binding characteristic of mithramycin and the covalent crosslinking to DNA of the Pt. The conjugate was three times as potent as cisplatin against ovarian cancer cells. The DNA lesions caused by the conjugate led to the generation of DNA double-strand breaks, as also observed with cisplatin. Nevertheless, the conjugate was highly active against both Pt-sensitive and Pt-resistant ovarian cancer cells. This study paves the way to developing mithplatins to combat Pt-resistant ovarian cancers.     

Proximity Coupling of Graphene to a Submonolayer 2D Magnet

Imprinting magnetism into graphene may lead to unconventional electron states and enable the design of spin logic devices with low power consumption. The ongoing active development of 2D magnets suggests their coupling with graphene to induce spin-dependent properties via proximity effects. In particular, the recent discovery of submonolayer 2D magnets on surfaces of industrial semiconductors provides an opportunity to magnetize graphene coupled with silicon. Here, synthesis and characterization of large-area graphene/Eu/Si(001) heterostructures combining graphene with a submonolayer magnetic superstructure of Eu on silicon are reported. Eu intercalation at the interface of the graphene/Si(001) system results in a Eu superstructure different from those formed on pristine Si in terms of symmetry. The resulting system graphene/Eu/Si(001) exhibits 2D magnetism with the transition temperature controlled by low magnetic fields. Negative magnetoresistance and the anomalous Hall effect in the graphene layer provide evidence for spin polarization of the carriers. Most importantly, the graphene/Eu/Si system seeds a class of graphene heterostructures based on submonolayer magnets aiming at applications in graphene spintronics.     

Hydroxylherderite (Ca2Be2P2O8(OH)2) stability under extreme conditions (up to 750°C/100 GPa)

Hydroxylherderite, Ca₂Be₂P₂O₈(OH)₂, is among the most common beryllophosphates in nature and could play a substantial role in Be geochemical cycle. Hydroxylherderite P–T stability and crystal structure behavior were studied under extreme conditions (up to 750°C/100 GPa) using in situ single-crystal and powder X-ray diffraction and Raman spectroscopy. The mineral demonstrated high stability under high-pressure conditions (up to ∼100 GPa) without any phase transitions. Under high-temperature conditions, it was stable up to about 700°C, when it decomposed with the formation of fluorapatite Ca₅(PO₄)₃F and hurlbutite CaBe₂P₂O₈. The beryllophosphate member of the gadolinite supergroup is the most stable mineral (material) under high-pressure conditions, compared to aluminum-, boro- and beryllosilicates.     

Molecular Architecture Effects on Bulk Nanostructure in Bis(Orthoborate) Ionic Liquids

A series of 19 ionic liquids (ILs) based on phosphonium and imidazolium cations of varying alkyl-chain lengths with the orthoborate anions bis(oxalato)borate [BOB]⁻, bis(mandelato)borate, [BMB]⁻ and bis(salicylato)borate, [BScB]⁻, are synthesized and studied using small-angle neutron scattering (SANS). All measured systems display nanostructuring, with 1-methyl-3-n-alkyl imidazolium-orthoborates forming clearly bicontinuous L₃ spongelike phases when the alkyl chains are longer than C₆ (hexyl). L₃ phases are fitted using the Teubner and Strey model, and diffusely-nanostructured systems are primarily fitted using the Ornstein-Zernicke correlation length model. Strongly-nanostructured systems have a strong dependence on the cation, with molecular architecture variation explored to determine the driving forces for self-assembly. The ability to form well-defined complex phases is effectively extinguished in several ways: methylation of the most acidic imidazolium ring proton, replacing the imidazolium 3-methyl group with a longer hydrocarbon chain, substitution of [BOB]⁻ by [BMB]⁻, or exchanging the imidazolium for phosphonium systems, irrespective of phosphonium architecture. The results suggest there is only a small window of opportunity, in terms of molecular amphiphilicity and cation:anion volume matching, for the formation of stable extensive bicontinuous domains in pure bulk orthoborate-based ILs. Particularly important for self-assembly processes appear to be the ability to form H-bonding networks, which offer additional versatility in imidazolium systems.