Quadratic and Cubic Optical Nonlinearities of Y-Shaped and Distorted-H-Shaped Arylalkynylruthenium Complexes.

Straightforward syntheses of bis[bis{1,2-bis(diphenylphosphino)ethane}ruthenium]-functionalized 1,3,5-triethynylbenzene-cored complexes via a methodology employing "steric control" permit facile formation of Y-shaped Sonogashira coupling products and distorted-H-shaped homo-coupled quadrupolar products. Cyclic voltammetric data from these products reveal two reversible metal alkynyl-localized oxidation processes for all complexes. The wavelengths of the linear optical absorption maxima are dominated by the nature of the peripheral alkynyl ligand rather than the substituent at the unique arm of the "Y" or at the quadrupolar complex "core". The quadratic optical nonlinearities of the Y-shaped complexes were assessed by the hyper-Rayleigh scattering technique at 800 nm and employing 100 fs light pulses; introduction of donor NEt2 and/or acceptor NO2 to the wedge periphery resulted in non-zero nonlinearities, with the largest ßHRS,800 values being observed for the complexes containing the 4-nitrophenylalkynyl ligands. Depolarization ratios are consistent with substantial off-diagonal first hyperpolarizability tensor components and 2D nonlinear character. Computational studies employing time-dependent density functional theory have been employed to assign the key low-energy transitions in the linear optical spectra and to compute the quadratic nonlinear optical tensorial components. Cubic optical nonlinearities of the quadrupolar complexes were assessed by the Z-scan technique over the range 500-1600 nm and employing 130 fs light pulses; two-photon absorption cross-sections for these distorted-H-shaped complexes are moderate to large in value (up to 5500 GM at 880 nm), while one example displays significant three-photon absorption (1300×10-80  cm6 s2 at 1200 nm).

Short communication: the cardiac myosin binding protein C Arg502Trp mutation: a common cause of hypertrophic cardiomyopathy.

RATIONALE: The myosin-binding protein C isoform 3 (MYBPC3) variant Arg502Trp has been identified in multiple hypertrophic cardiomyopathy (HCM) cases, but compelling evidence to support or refute the pathogenicity of this variant is lacking. OBJECTIVE: To determine the prevalence, origin and clinical significance of the MYBPC3 Arg502Trp variant. METHODS AND RESULTS: The prevalence of MYBPC3 Arg502Trp was ascertained in 1414 sequential HCM patients of primarily European descent. MYBPC3 Arg502Trp was identified in 34 of these 1414 unrelated HCM patients. Segregation of MYBPC3 Arg502Trp with clinical status was assessed in family members. Disease haplotypes were examined in 17 families using two loci flanking MYBPC3. Family studies identified an additional 43 variant carriers, many with manifest disease, yielding a calculated odds ratio of 11 000:1 for segregation of MYBPC3 Arg502Trp with HCM. Analyses in 17 families showed at least 4 independent haplotypes flanked MYBPC3 Arg502Trp. Eight individuals (4 probands and 4 family members) also had another sarcomere protein gene mutation. Major adverse clinical events occurred in approximately 30% of MYBPC3 Arg502Trp carriers by age 50; these were significantly more likely (P<0.0001) when another sarcomere mutation was present. CONCLUSIONS: MYBPC3 Arg502Trp is the most common and recurrent pathogenic mutation in a diverse primarily European descent HCM cohort, occurring in 2.4% of patients. MYBPC3 Arg502Trp conveys a 340-fold increased risk for HCM by 45 years of age, when more than 50% of carriers have overt disease. HCM prognosis worsens when MYBPC3 Arg502Trp occurs in the setting of another sarcomere protein gene mutation.

Effect of pnictogen ligand substitution on a tripalladium ditropylium core.

A combination of multinuclei NMR, UV-vis spectroscopy, and single crystal X-ray diffraction was used to characterize a new series of tripalladium ditropylium sandwich complexes [Pd(3)Tr(2)(E)(3)][BF(4)](2) (E = PPh(3), AsPh(3), and SbPh(3) and PEt(3)). Ligand substitution leads to a systematic shift of the (1)H and (13)C NMR tropylium resonances and is correlated with the electron donating properties of the substituent group. Replacement of the ligand increases the palladium-pnictogen bond length in the order P < As < Sb; however, this only slightly alters the internal Pd-Pd bond lengths, supporting the hypothesis that there are only weak Pd-Pd bonding interactions.

Monomers and polymers of tripalladium(0) ditropylium halides.

The synthesis and characterization of a series of polymeric complexes based upon a central tripalladium ditropylium (Tr) unit [Pd(3)Tr(2)] and containing different halide ligands are reported. The complexes were synthesized in good yield and characterized by multinuclei NMR spectroscopy, mass spectrometry, microanalysis, and X-ray crystallography. An unexpected product was an inorganic polymer consisting of linked individual tripalladium ditropylium units [Pd(3)Tr(2)X(2)](infinity) (X = Cl, Br, and I); this is the first reported, crystallographically characterized example of polymeric tripalladium complexes with halide ligands.

Cornelia de Lange syndrome (CdLS): prenatal and autopsy findings.

Cornelia de Lange Syndrome (CdLS) is a multisystem disorder characterized by somatic defects and mental retardation. Prenatal diagnosis of this severe condition is difficult in view of the non-specific ultrasound abnormalities. We report three cases with prenatally suspected CdLS based on the ultrasound findings as well as low PAPP-A detected on first trimester screening in one case, and the results of the autopsy and the NIPBL gene mutation analysis.

Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas.

Constitutional SMARCB1 mutations at 22q11.23 have been found in ∼50% of familial and <10% of sporadic schwannomatosis cases. We sequenced highly conserved regions along 22q from eight individuals with schwannomatosis whose schwannomas involved somatic loss of one copy of 22q, encompassing SMARCB1 and NF2, with a different somatic mutation of the other NF2 allele in every schwannoma but no mutation of the remaining SMARCB1 allele in blood and tumor samples. LZTR1 germline mutations were identified in seven of the eight cases. LZTR1 sequencing in 12 further cases with the same molecular signature identified 9 additional germline mutations. Loss of heterozygosity with retention of an LZTR1 mutation was present in all 25 schwannomas studied. Mutations segregated with disease in all available affected first-degree relatives, although four asymptomatic parents also carried an LZTR1 mutation. Our findings identify LZTR1 as a gene predisposing to an autosomal dominant inherited disorder of multiple schwannomas in ∼80% of 22q-related schwannomatosis cases lacking mutation in SMARCB1.

Quantifying the carrier female phenotype in Pelizaeus-Merzbacher disease.

PURPOSE: Pelizaeus-Merzbacher disease and spastic paraplegia type 2 are allelic X-linked disorders that principally affect males and are caused by mutations in the proteolipid protein 1 gene. Neurologic symptoms are occasionally observed in carrier females, and anecdotal evidence suggests that these clinical signs are more likely in families with affected males. We analyze 40 pedigrees to determine whether such a link exists. METHODS: From a chart review of patients from Wayne State University, we categorize patients according to disease severity and type of genetic lesion within the proteolipid protein 1 gene. We then analyze the clinical data using nonparametric t tests and analyses of variance. RESULTS: Our analyses formally demonstrate the link between mild disease in males and symptoms in carrier female relatives. Conversely, mutations causing severe disease in males rarely cause clinical signs in carrier females. The greatest risk of disease in females is found for nonsense/indel or null mutations. Missense mutations carry moderate risk. The lowest risk, which represents the bulk of families with Pelizaeus-Merzbacher disease, is associated with proteolipid protein 1 gene duplications. CONCLUSIONS: Effective genetic counseling of Pelizaeus-Merzbacher disease and spastic paraplegia carrier females must include an assessment of disease severity in affected male relatives.