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1.
Chemistry ; 26(49): 11180-11186, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-32315484

ABSTRACT

Herein, we establish the preparation, characterization, and reactivity of a new diphosphine ligand, 1,2-bis(di(3-dicyclohexylboraneyl)propylphosphino)ethane (P2 BCy 4 ), a scaffold that contains four pendant boranes. An entryway into the coordination chemistry of P2 BCy 4 is established by using nickel, providing the octaboraneyl complex [Ni(P2 BCy 4 )2 ]-this species contains a boron-rich secondary coordination sphere that reacts readily with Lewis bases. In the case of 4,4'-bipyridine, an air-sensitive coordination polymer is obtained. Characterization of this material by solid-state NMR and EPR spectroscopy reveals the presence of a charge-transfer polymer, which forms as a function of intramolecular Ni→4,4'-bpy electron transfer (ET), providing an array of oxidized nickel sites and reduced 4,4'-bpy radical anion sites. Notably, the related intermolecular reaction between the model fragments [Ni(dnppe)2 ] (dnppe=1,2-bis(di-n-propylphosphino)ethane) and a bis(boraneyl)-protected 4,4'-bpy, provides no ET. Overall, the P2 BCy 4 fragment provides a unique opportunity for Lewis base activation, in one case allowing for the facile construction of monomers for incorporation into redox-active macromolecules.

2.
Solid State Nucl Magn Reson ; 101: 101-109, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31150959

ABSTRACT

The structural and electronic properties of solid coordination compounds are of great interest in a wide variety of applications. The sensitivity of solid-state NMR to local structural environments in the presence of a transition metal with unpaired spins is demonstrated through 13C and 1H MAS NMR spectra of tris(acetylacetonato)manganese (III), Mn(acac)3. The spectral assignment is established using a combination of density-functional theory and experimental NMR methods. An analysis of the spin-density distribution throughout the ligands as probed by NMR provides an understanding of the molecular electronic structure. The paramagnetic interaction enhances the spectral resolution and offers the possibility of using these spectra as structural fingerprints. The unique character of Mn(acac)3 to manifest various degrees of Jahn-Teller distortions allows for a discussion of the relation between the electron occupancy, crystal structure, and 13C NMR peak shifts.

3.
Cancer Res ; 73(2): 776-84, 2013 Jan 15.
Article in English | MEDLINE | ID: mdl-23135916

ABSTRACT

Neuroblastoma is uniquely sensitive to single-agent inhibition of the DNA damage checkpoint kinase Chk1, leading us to examine downstream effectors of this pathway and identify mitotic regulator Wee1 as an additional therapeutic target in this disease. Wee1 was overexpressed in both neuroblastoma cell lines and high-risk patient tumors. Genetic or pharmacologic abrogation of Wee1 signaling results in marked cytotoxicity in 10 of 11 neuroblastoma cell lines with a median IC(50) of 300 nmol/L for the Wee1-selective small-molecule inhibitor MK-1775. Murine tumor lines derived from mice that were either heterozygous or homozygous for MycN were particularly sensitive to single-agent inhibition of Wee1 (IC(50)s of 160 and 62 nmol/L, respectively). Simultaneous pharmacologic inhibition of Chk1 and Wee1 acted in a synergistic fashion to further impede neuroblastoma cell growth in vitro, in a manner greater than the individual inhibitors either alone or combined with chemotherapy. Combination Chk1 and Wee1 inhibition also revealed in vivo efficacy in neuroblastoma xenografts. Taken together, our results show that neuroblastoma cells depend on Wee1 activity for growth and that inhibition of this kinase may serve as a therapeutic for patients with neuroblastoma.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Cycle Proteins/antagonists & inhibitors , Neuroblastoma/drug therapy , Nuclear Proteins/antagonists & inhibitors , Protein Kinase Inhibitors/therapeutic use , Protein Kinases/drug effects , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrazoles/administration & dosage , Pyrimidines/administration & dosage , Animals , Cell Line, Tumor , Checkpoint Kinase 1 , Female , Humans , Mice , Mice, SCID , Pyrimidinones , Xenograft Model Antitumor Assays
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