Sum Rules for Multi-Photon Spectroscopy of Ions in Finite Symmetry

Models describing one- and two-photon transitions for ions in crystalline environments are unified and extended to the case of parity-allowed and parity- forbidden p-photon transitions. The number of independent parameters for characterizing the polarization dependence is shown to depend on an ensemble of properties and rules which combine symmetry considerations and physical models.Comment: 16 pages, Tex fil

Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader–Willi syndrome

Prader–Willi syndrome (PWS) is an imprinting disorder caused by a deficiency of paternally expressed gene(s) in the 15q11–q13 chromosomal region. The regulation of imprinted gene expression in this region is coordinated by an imprinting center (PWS-IC). In individuals with PWS, genes responsible for PWS on the maternal chromosome are present, but repressed epigenetically, which provides an opportunity for the use of epigenetic therapy to restore expression from the maternal copies of PWS-associated genes. Through a high-content screen (HCS) of >9,000 small molecules, we discovered that UNC0638 and UNC0642—two selective inhibitors of euchromatic histone lysine N-methyltransferase-2 (EHMT2, also known as G9a)—activated the maternal (m) copy of candidate genes underlying PWS, including the SnoRNA cluster SNORD116, in cells from humans with PWS and also from a mouse model of PWS carrying a paternal (p) deletion from small nuclear ribonucleoprotein N (Snrpn (S)) to ubiquitin protein ligase E3A (Ube3a (U)) (mouse model referred to hereafter as m+/pΔS−U). Both UNC0642 and UNC0638 caused a selective reduction of the dimethylation of histone H3 lysine 9 (H3K9me2) at PWS-IC, without changing DNA methylation, when analyzed by bisulfite genomic sequencing. This indicates that histone modification is essential for the imprinting of candidate genes underlying PWS. UNC0642 displayed therapeutic effects in the PWS mouse model by improving the survival and the growth of m+/pΔS−U newborn pups. This study provides the first proof of principle for an epigenetics-based therapy for PWS

Structural Elucidation of Cisoid and Transoid Cyclization Pathways of a Sesquiterpene Synthase Using 2-Fluorofarnesyl Diphosphates

Sesquiterpene skeletal complexity in nature originates from the enzyme-catalyzed ionization of (<i>trans</i>,<i>trans</i>)-farnesyl diphosphate (FPP) (<b>1a</b>) and subsequent cyclization along either 2,3-transoid or 2,3-cisoid farnesyl cation pathways. Tobacco 5-epi-aristolochene synthase (TEAS), a transoid synthase, produces cisoid products as a component of its minor product spectrum. To investigate the cryptic cisoid cyclization pathway in TEAS, we employed (<i>cis</i>,<i>trans</i>)-FPP (<b>1b</b>) as an alternative substrate. Strikingly, TEAS was catalytically robust in the enzymatic conversion of (<i>cis</i>,<i>trans</i>)-FPP (<b>1b</b>) to exclusively (≥99.5%) cisoid products. Further, crystallographic characterization of wild-type TEAS and a catalytically promiscuous mutant (M4 TEAS) with 2-fluoro analogues of both all-<i>trans</i> FPP (<b>1a</b>) and (<i>cis</i>,<i>trans</i>)-FPP (<b>1b</b>) revealed binding modes consistent with preorganization of the farnesyl chain. These results provide a structural glimpse into both cisoid and transoid cyclization pathways efficiently templated by a single enzyme active site, consistent with the recently elucidated stereochemistry of the cisoid products. Further, computational studies using density functional theory calculations reveal concerted, highly asynchronous cyclization pathways leading to the major cisoid cyclization products. The implications of these discoveries for expanded sesquiterpene diversity in nature are discussed

Bonding Trends in Molecular Compounds of Lanthanides: The Double-Bonded Carbene Cations LnCH(2) (+) (Ln=Sc, Y, La-Lu).

Quasi-relativistic Douglas-Kroll CASPT2 calculations are reported for the title molecules, mainly to provide primary data for a fit of double-bond covalent radii. Indeed, a well-developed sigma(2)pi(2) double bond is identified in all cases. For Eu and Yb, however, it is an excited state. The main valence orbitals of all Ln ions are 6s and 5d. In the sigma bonds, more 5d than 6s character is found at the Ln. The Ln==C bond lengths show a systematic lanthanide contraction of 13 pm from La to Lu. An agostic symmetry breaking is demonstrated for Ce but its effect on the Ln--C length is small

Investigation into the Effects of a Trigonal Planar Ligand Field on the Electronic Properties of Lanthanide(II) Tris(silylamide) Complexes (Ln = Sm, Eu, Tm, Yb)

In recent work we have reported the synthesis and physical properties of near-linear Ln­(II) (Ln = lanthanide) complexes utilizing the bulky bis­(silylamide) {N­(Si^<i>i</i>Pr₃)₂}. Herein, we synthesize trigonal-planar Ln­(II) complexes by employing a smaller bis­(silylamide), {N­(Si^<i>t</i>BuMe₂)₂} (N**), to study the effects of this relatively rare Ln geometry/oxidation state combination on the magnetic and optical properties of complexes. We show that the charge-separated trigonal-planar Ln­(II) complexes [K­(2.2.2-cryptand)]­[Ln­(N**)₃] (Ln = Sm (<b>1</b>), Eu (<b>2</b>), Tm (<b>3</b>), Yb (<b>4</b>)) can be prepared by the reaction of 1.5 equiv of [{K­(N**)}₂] with LnI₂THF₂ (Ln = Sm, Yb) or LnI₂ (Ln = Eu, Tm) and 1 equiv of 2.2.2-cryptand in Et₂O. Complex <b>3</b> is the first structurally characterized trigonal-planar Tm­(II) complex. In the absence of 2.2.2-cryptand, [K­(DME)₃]­[Sm­(N**)₃] (<b>5</b>) and [Ln­(N**)₂(μ-N**)­K­(toluene)₂] (Ln = Sm (<b>6</b>), Eu (<b>7</b>)) were isolated in the presence of DME (dimethoxyethane) or toluene, respectively. The 1:1 reaction of [{K­(N**)}₂] with LnI₂THF₂ (Ln = Sm, Yb) in THF gave the four-coordinate pseudo-tetrahedral Lewis base adducts [Ln­(N**)₂(THF)₂] (Ln = Sm (<b>8</b>), Yb (<b>9</b>)) and the cyclometalated complex [Yb­(N**)­{N­(Si^<i>t</i>BuMe₂)­(Si^<i>t</i>BuMeCH₂)}­(THF)] (<b>10</b>). Complexes <b>1</b>–<b>10</b> have been characterized as appropriate by single-crystal XRD, magnetic measurements, multinuclear NMR, EPR, and electronic spectroscopy, together with CASSCF-SO and DFT calculations. The physical properties of <b>1</b>–<b>4</b> are compared and contrasted with those of closely related near-linear Ln­(II) bis­(silylamide) complexes