Synthesis of Calcium(II) Amidinate Precursors for Atomic Layer Deposition through a Redox Reaction between Calcium and Amidines

We have prepared two new Ca^II amidinates, which comprise a new class of ALD precursors. The syntheses proceed by a direct reaction between Ca metal and the amidine ligands in the presence of ammonia. Bis(N,N′‐diisopropylformamidinato)calcium(II) ( 1 ) and bis(N,N′‐diisopropylacetamidinato)calcium(II) ( 2 ) adopt dimeric structures in solution and in the solid state. X‐ray crystallography revealed asymmetry in one of the bridging ligands to afford the structure [(η²‐L)Ca(μ‐η²:η²‐L)(μ‐η²:η¹‐L)Ca(η²‐L)]. These amidinate complexes showed unprecedentedly high volatility as compared to the widely employed and commercially available Ca^II precursor, [Ca₃(tmhd)₆]. In CaS ALD with 1 and H₂S, the ALD window was approximately two times wider and lower in temperature by about 150 °C than previously reported with [Ca₃(tmhd)₆] and H₂S. Complexes 1 and 2 , with their excellent volatility and thermal stability (up to at least 350 °C), are the first homoleptic Ca^II amidinates suitable for use as ALD precursors.     

Solid-Phase Synthesis and Encoding Strategies for Olefin Polymerization Catalyst Libraries

Active polymerization catalysts , novel resin-bound diimine complexes of nickel(II ) and palladium(II ) are obtained by combinatorial synthesis and combined in a catalyst library. By tagging with fluorescent markers, the catalysts can be coded. Therefore, after cleavage of the tag from the polymer-coated resin, HPLC can be used to determine the pathway along which the products were formed.     

Exploiting Incommensurate Symmetry Numbers: Rational Design and Assembly of M2M3′L6 Supramolecular Clusters with C3h Symmetry

Mixed-metal mesocates [M₂Pd₃Br₆L₆]⁴⁻ (M=Ti^IV, Sn^IV; L=4-diphenylphosphanyl-catecholate) have been synthesized, in which the two incommensurate symmetry elements generated by the different metal ions are linked by a rigid, bifunctional ligand to generate a C_3h-symmetrical cluster (see picture).     

Recreational runners with patellofemoral pain exhibit elevated patella water content

Increased bone water content resulting from repetitive patellofemoral joint overloading has been suggested to be a possible mechanism underlying patellofemoral pain (PFP). To date, it remains unknown whether persons with PFP exhibit elevated bone water content. The purpose of this study was to determine whether recreational runners with PFP exhibit elevated patella water content when compared to pain-free controls. Ten female recreational runners with a diagnosis of PFP (22 to 39 years of age) and 10 gender, age, weight, height, and activity matched controls underwent chemical-shift-encoded water-fat magnetic resonance imaging (MRI) to quantify patella water content (i.e., water-signal fraction). Differences in bone water content of the total patella, lateral aspect of the patella, and medial aspect of the patella were compared between groups using independent t tests. Compared with the control group, the PFP group demonstrated significantly greater total patella bone water content (15.4 ± 3.5% vs. 10.3 ± 2.1%; P = 0.001), lateral patella water content (17.2 ± 4.2% vs. 11.5 ± 2.5%; P = 0.002), and medial patella water content (13.2 ± 2.7% vs. 8.4 ± 2.3%; P < 0.001). The higher patella water content observed in female runners with PFP is suggestive of venous engorgement and elevated extracellular fluid. In turn, this may lead to an increase in intraosseous pressure and pain.     

Validity and Reliability of the Reflux Symptom Index (RSI)

Laryngopharyngeal reflux (LPR) is present in up to 50% of patients with voice disorders. Currently, there is no validated instrument that documents symptom severity in LPR. We developed the reflux symptom index (RSI), a self-administered nine-item outcomes instrument for LPR. The purpose of this investigation was to evaluate the psychometric properties of the RSI. For validity assessment, 25 patients with LPR were evaluated prospectively before and six months after b.i.d. treatment with proton pump inhibitors (PPI). Each patient completed the RSI as well as the 30-item voice handicap index (VHI). For reliability assessment, the study patients were given the RSI on two separate occasions before the initiation of treatment. Normative RSI data were derived from 25 age-matched and gender-matched controls taken from an existing database of asymptomatic individuals without any evidence of LPR. The mean RSI (+/- standard deviation) of patients with LPR improved from 21.2 (+/- 10.7) to 12.8 (+/- 10.0), and the mean VHI improved from 52.2 (+/- 24.7) to 41.5 (+/- 25.0) after 6 months of therapy (p = 0.001 and 0.065, respectively). Of the three VHI subscales (emotional, physical, functional), only the functional subscale improved significantly (p = 0.037). Patients who experienced a five point or better improvement in RSI were 11 times more likely to experience a five-point improvement in VHI (95% confidence interval = 1.7, 76.8). For reliability assessment, the first and second pretreatment RSIs were 19.9 (+/- 11.1) and 20.9 (+/- 9.6), respectively (correlation coefficient = 0.81, p < 0.001). The single-item correlation coefficients ranged from 0.41 to 0.91 (p < 0.05 for all items). The mean pretreatment RSI in patients with LPR was significantly higher than controls (21.2 versus 11.6; p < 0.001). The mean RSI of patients with LPR after 6 months of PPI therapy approached that of asymptomatic controls (p > 0.05). The RSI is easily administered, highly reproducible, and exhibits excellent construct and criterion-based validity.     

Fibronectin: An Interesting Vocal Fold Protein

A great deal of information is accruing regarding the function of the extracellular matrix. Once thought to be simply a structural entity to surround cells, it is now known to do much more. Fibronectin in particular has received specific attention. Fibronectin is a ubiquitous glycoprotein found most abundantly in the extracellular matrix of regenerating, healing, and embryonic tissue. Vast evidence supports the fact that fibronectin participates in many diverse functions throughout the body that are relevant to vocal fold biology. This article introduces the structure of fibronectin and its isoforms and provides an introduction to some of the many functions it plays. It also reviews the evidence about fibronectin's place in vocal folds and vocal fold pathology. It discusses fibronectin's presence in vocal nodules, vocal polyps, vocal scarring, and Reinke's edema, and reviews the data on its role in mucosal wave impairment. Lastly, it discusses preliminary microarray data that show gene expression for fibronectin to be upregulated in true vocal folds when compared to false vocal folds.     

Short-Term Therapeutic Trial of Proton Pump Inhibitors in Suspected Extraesophageal Reflux

Pharyngoesophageal gastric acid reflux is thought to initiate chronic posterior laryngitis. The gold standard for measuring gastric reflux is dual-channel 24-hour pH monitoring. This is a time-consuming, inconvenient, expensive method that is not available in all areas. New therapeutic regimes that make use of proton pump inhibitors (PPIs) have proven to be therapeutically efficient for control of acid reflux. Twenty-four consecutive patients with chronic voice disorders and signs of posterior laryngitis were selected for therapy. Twenty-four hour pH monitoring was performed independently before the therapy. The trial therapy consisted of all patients receiving pantoprazole, 40 mg once daily for 6 weeks. Immediately following the therapy a statistically significant (p < 0.05) improvement was observed in all patients. This improvement was analyzed retrospectively by comparison with the results of 24-hour pH monitoring. In 71% of the patients the 24-hour pH-monitoring gave a positive result showing a high number of patients with extraesophageal reflux in our study group. Patients with positive results of pH-monitoring responded in a statistically significant manner (p < 0.05) to the pantoprazole therapy, whereas those patients without detected reflux did not. A 3-month follow-up of the patients with a positive result of the pH-monitoring confirmed the improvement. No patients reported adverse effects. A 6-week treatment with pantoprazole can be clinically justified. It helps to save time and reduce costs, allows for selection of reflux-negative patients for alternative therapy, and may prevent inadequate treatment of patients with false-negative pH monitoring. Twenty-four hour pH monitoring is still recommended for patients unresponsive to this trial therapy.     

Utilization of phosphinoamide ligands in homobimetallic fe and mn complexes: the effect of disparate coordination environments on metal-metal interactions and magnetic and redox properties

A series of homobimetallic phosphinoamide-bridged diiron and dimanganese complexes in which the two metals maintain different coordination environments have been synthesized. Systematic variation of the steric and electronic properties of the phosphinoamide phosphorus and nitrogen substituents leads to structurally different complexes. Reaction of [(i)PrNKPPh(2)] (1) with MCl(2) (M = Mn, Fe) affords the phosphinoamide-bridged bimetallic complexes [Mn((i)PrNPPh(2))(3)Mn((i)PrNPPh(2))] (3) and [Fe((i)PrNPPh(2))(3)Fe((i)PrNPPh(2))] (4). Complexes 3 and 4 are iso-structural, with one metal center preferentially binding to the three amide ligands in a trigonal planar arrangement while the second metal center is ligated by three phosphine donors. A fourth phosphinoamide ligand caps the tetrahedral coordination sphere of the phosphine-ligated metal center. M?ssbauer spectroscopy of complex 4 suggests that the metals in these complexes are best described as Fe(II) centers. In contrast, treatment of MnCl(2) or FeI(2) with [MesNKP(i)Pr(2)] (2) leads to the formation of the halide-bridged species [(THF)Mn(μ-Cl)(MesNP(i)Pr(2))(2)Mn(MesNP(i)Pr(2))] (5) and [(THF)Fe(μ-I)(MesNP(i)Pr(2))(2)FeI (7), respectively. Utilization of FeCl(2) in place of FeI(2), however, leads exclusively to the C(3)-symmetric complex [Fe(MesNP(i)Pr(2))(3)FeCl] (6), structurally similar to 4 but with a halide bound to the phosphine-ligated Fe center. The M?ssbauer spectrum of 6 is also consistent with high spin Fe(II) centers. Thus, in the case of the [(i)PrNPPh(2)](-) and [MesNP(i)Pr(2)](-) ligands, zwitterionic complexes with the two metals in disparate coordination environments are preferentially formed. In the case of the more electron-rich ligand [(i)PrNP(i)Pr(2)](-), complexes with a 2:1 mixed donor ligand arrangement, in which one of the ligand arms has reversed orientation relative to the previous examples, are formed exclusively when [(i)PrNLiP(i)Pr(2)] (generated in situ) is treated with MCl(2) (M = Mn, Fe): (THF)(3)LiCl[Mn(N(i)PrP(i)Pr(2))(2)(P(i)Pr(2)N(i)Pr)MnCl] (8) and [Fe(N(i)PrP(i)Pr(2))(2)(P(i)Pr(2)N(i)Pr)FeCl] (9). Bimetallic complexes 3-9 have been structurally characterized using X-ray crystallography, revealing Fe-Fe interatomic distances indicative of metal-metal bonding in complexes 6 and 9 (and perhaps 4, to a lesser extent). All of the complexes appear to adopt high spin electron configurations, and magnetic measurements indicate significant antiferromagnetic interactions in Mn(2) complexes 5 and 8 and no discernible magnetic superexchange in Fe(2) complex 4. The redox behavior of complexes 3-9 has also been investigated using cyclic voltammetry, and theoretical investigations (DFT) were performed to gain insight into the metal-metal interactions in these unique asymmetric complexes.     

Incorporating beta-turns and a turn mimetic out of context in loop 1 of the WW domain affords cooperatively folded beta-sheets.

To probe the conformational requirements of loop 1 in the Pin1 WW domain, the residues at the i + 2 and i + 3 positions of a beta-turn within this loop were replaced by dPro-Gly and Asn-Gly, which are known to prefer the conformations required at the i + 1 and i + 2 positions of type II' and type I' beta-turns. Conformational specificity or lack thereof was further examined by incorporating into the i + 2 and i + 3 positions a non-alpha-amino acid-based beta-turn mimetic (4-(2'-aminoethyl)-6-dibenzofuran propionic acid residue, 1), which was designed to replace the i + 1 and i + 2 positions of beta-turns. All these Pin WW variants are monomeric and folded as discerned by analytical ultracentrifugation, NMR, and CD. They exhibit cooperative two-state transitions and display thermodynamic stability within 0.5 kcal/mol of the wild-type WW domain, demonstrating that the acquisition of native structure and stability does not require a specific sequence and, by extension, conformation within loop 1. However, it could be that these loop 1 mutations alter the kinetics of antiparallel beta-sheet folding, which will be addressed by subsequent kinetic studies.