Reply to A Computational Evaluation of the Evidence for the Synthesis of 1,3‐Dimethylcyclobutadiene in Solid State and Aqueous Solution—Beyond the Experimental Reality

Following earlier reports on the photochemical synthesis of 1,3‐dimethylcyclobutadiene 8 , 10 in a protective host matrix, theoretical calculations for the formation of that adduct have been recently performed by Rzepa. 13 The author formulated criticisms based mainly on density functional theory calculations of ¹H NMR spectra. According to Rzepa the calculated spectra do not correspond with our measured spectra, which leads him to the conclusion that our interpretation is wrong, and that mainly cyclobutadiene has not been stabilized or even synthesized; we believe, however, that the initial model that Rzepa used for his calculations does not correspond to chemical reality or is at the very least a crude simplification of it, which implies that his calculations cannot match, in every point, our experimental spectra. Rzepa′s simplified models might be ‘reasonable’ from the theoretical point of view; however, in the case of assessment in the solid state, the theoretical setup does not force the system to preserve the confined stabilizing space defined by the crystalline matrix for encapsulated hosts in the solid state. Inversely, in the case of solution modeling, the theoretical setup is too rigid to properly assess the complex equilibria occurring in solution and to accurately determine the NMR spectra of exchanging species in solution. The inconsistency between our experimental results and the results of the theoretical models proposed by Rzepa is such that his conclusions are considered to be too far from experimental reality. Accurate modeling taking in account “reasonable” experimental details would be a worthwhile endeavor.     

X‐Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists

We present a robust protocol based on iterations of free energy perturbation (FEP) calculations, chemical synthesis, biophysical mapping and X‐ray crystallography to reveal the binding mode of an antagonist series to the A_2A adenosine receptor (AR). Eight A_2AAR binding site mutations from biophysical mapping experiments were initially analyzed with sidechain FEP simulations, performed on alternate binding modes. The results distinctively supported one binding mode, which was subsequently used to design new chromone derivatives. Their affinities for the A_2AAR were experimentally determined and investigated through a cycle of ligand‐FEP calculations, validating the binding orientation of the different chemical substituents proposed. Subsequent X‐ray crystallography of the A_2AAR with a low and a high affinity chromone derivative confirmed the predicted binding orientation. The new molecules and structures here reported were driven by free energy calculations, and provide new insights on antagonist binding to the A_2AAR, an emerging target in immuno‐oncology.     

A marked difference between two populations under mass screening of neonatal TSH and biotinidase activity

Health-associated reference values are universally needed in clinical chemistry. The aim of this study was to establish the reference intervals of two populations from data obtained by the mass screening of newborn babies and to demonstrate how to determine 95% confidence intervals around the lower and upper limits of reference values from values that are not normally distributed. Biotinidase activities from Belgian (n=260) and Turkish (n=328) populations were measured by fluorometric assay and expressed as 1 IU (1 nmol/(dl min). Neonatal thyroid-stimulating hormone (nTSH) values from Belgian (n=4186) and Turkish (n=1663) populations were also measured by the solid phase two-site fluoroimmunometric assay, the results were given as μU/ml blood. Transformation of data was performed for each parameter. A parametric method was used for determination of reference values of biotinidase activity and the Belgian population was significantly higher than the Turkish population. nTSH reference values were evaluated by an exact non-parametric method, but approximate calculation based on the central limit theorem was also performed for confidence intervals around the reference limits. nTSH values of the Turkish population were found to be significantly higher than for the Belgian population. Rank numbers were found by an exact non-parametric method based upon the assumption of a binomial distribution. This study shows a procedure to define the rank numbers for n>1000 and to obtain reference values with 95% confidence intervals for lower and upper reference limits. Received: 20 July 2002 Accepted: 27 July 2002 Acknowledgements We are grateful to Professor Per Hyloft Peterson, Clinical Biochemist, Odense University Hospital, for his valuable advice and criticism. Also we would like to thank John Pezzullo Associate Professor for Pharmacology and Biostatistics, at Georgetown University Medical Center, for his binomial and approximate calculations. We also want to thank Professor Fatma Kutay, Clinical Chemist, Ege University Medical School and Hospital, for her contributions. This investigation was supported in part by a short term FEBS (Federation European Biochemical Society) fellowship grant. Presented at the European Conference on Quality in the Spotlight in Medical Laboratories, 7–9 October 2001, Antwerp, Belgium Correspondence to T. Tanyal?ın     

Self-assembled monolayers of alkylphosphonic acid on GaN substrates

In this paper we describe the formation and characterization of self-assembled monolayers of octadecylphosphonic acid (ODPA) on epitaxial (0001) GaN films on sapphire. By immersing the substrate in its toluene solution, ODPA strongly adsorbed onto UV/O 3-treated GaN to give a hydrophobic surface. Spectroscopic ellipsometry verified the formation of a well-packed monolayer of ODPA on the GaN substrate. In contrast, adsorption of other primarily substituted hydrocarbons (C n H 2 n+1 X; n = 16-18; X = -COOH, -NH 2, -SH, and -OH) offered less hydrophobic surfaces, reflecting their weaker interaction with the GaN substrate surfaces. A UV/O 3-treated N-polar GaN had a high affinity to the -COOH group in addition to ODPA, possibly reflecting the basic properties of the surface. These observations suggested that the molecular adsorption was primarily based on hydrogen bond interactions between the surface oxide layer on the GaN substrate and the polar functional groups of the molecules. The as-prepared ODPA monolayers were desorbed from the GaN substrates by soaking in an aqueous solution, particularly in a basic solution. However, ODPA monolayers heated at 160 degrees C exhibited suppressed desorption in acidic and neutral aqueous solution maybe due to covalent bond formation between ODPA and the surface. X-ray photoelectron spectroscopy provided insight into the effect of the UV/O 3 treatment on the surface composition of the GaN substrate and also the ODPA monolayer formation. These results demonstrate that the surface of a GaN substrate can be tailored with organic molecules having an alkylphosphonic acid moiety for future sensor and device applications.     

Selective polarization transfer using a single rf field

NMR is a popular and mature technique used in fields as diverse as chemistry, biology, or material science. One reason for this versatility lies in its ability to correlate the nuclei that are present in one molecule to another. This provides the researcher with correlation maps allowing for studies of the molecules at an atomic level. Selective experiments allow isolation of one such correlation to focus on spins of interest. This leads to a savings in precious experimental time by reducing the dimension of the experiment, which in turn may enable one to record more elaborate experiments that would otherwise not be amenable within reasonable acquisition times. Here, we present an alternative method to selectively transfer magnetization using a single rf field. This technique, which we call single field polarization transfer, allows to obtain longitudinal two-spin order of two scalar-coupled spins when only one of them is irradiated. The method is easy to implement and does not depend on stringent conditions, such as Hartmann-Hahn matching for selective cross-polarization transfers or very long inversion pulses and identification of coupling satellites in selective population inversion experiments.     

1,10-Phenanthroline and 1,10-phenanthroline-terminated ruthenium(II) complex as efficient capping agents to stabilize gold nanoparticles: application for reversible aqueous-organic phase transfer processes

1,10-Phenanthroline (phen) and 1,10-phenanthroline-terminated ruthenium(II) complex [Ru-Lphen](2+) have been used to stabilize and functionalize gold nanoparticles (Au-NPs). The strong interaction between the nitrogen atoms of phen and the surface of Au-NPs allowed for the phase transfer of Au-NPs from toluene to aqueous phase containing [Ru-Lphen](2+). Reverse phase transfer of these Au-NPs from water to acetonitrile by substituting the Cl(-) counter anion by PF(-)(6) has also been demonstrated. Such facile post-functionalization, phase transfer and solvent transfer processes using metallic complexes bearing a terminal phenanthroline pendant group constitute a prerequisite for further studies of the electronic and optical properties of these NCs in various media.     

Silver-catalyzed one-pot synthesis of arylnaphthalene lactones

Arylnaphthalene lignan lactones are valuable natural products with promising anticancer and antiviral properties. In an effort to simplify their synthesis, we investigated a one-pot multicomponent coupling reaction between phenylacetylene, carbon dioxide, and 3-bromo-1-phenyl-1-propyne. After the corresponding 1,6-diyne was generated in situ, cyclization afforded the desired product. The level of regioselectivity was enhanced through the tuning of electronic properties. The use of cinnamyl bromide which led to the formation of a 1,6-enyne intermediate was also studied.     

Synthesis and structures of new binuclear zinc alkyl,aryl and aryloxo complexes

The synthesis of a series of binuclear zinc complexes with Cl, N and O bridges is reported. The reaction of EtZnCl with B(C₆F₅)₃ in the presence of hexamethylbenzene affords the arene complex [Zn(μ-Cl)(C₆F₅)(η-C₆Me₆)]₂ in which the C₆Me₆ ligand may be regarded as η³-bonded. The comproportionation of Zn[N(SiMe₃)₂]₂ with ZnBu^t₂ or Zn(C₆F₅)₂ · toluene gave [Bu^tZn{μ-N(SiMe₃)₂}]₂ and [C₆F₅Zn{μ-N(SiMe₃)₂}]₂, respectively, with three-coordinate zinc. The reaction of ZnEt₂ with C₆F₅OH in the presence of pyridine gave [EtZn(μ-OC₆F₅)(py)]₂, while ZnMe₂ and C₆F₅OH followed by recrystallisation from THF gave [Zn(OC₆F₅)(μ-OC₆F₅)(THF)₂]₂ with five-coordinate zinc in a trigonal-bipyramidal geometry. The structures of these compounds have been determined.