Water and the Huisgen Cycloaddition Reaction: A Focus on Polar Contributions to the Transition State in the Reactions of Dicyano(phthalazinium)methanide with Substituted Styrenes and Benzylidene Acetones

Synthetic and kinetic studies on the 1,3‐dipolar cycloaddition reactions of dicyano(phthalazin‐2‐ium‐2‐yl)methanide ( 1 ) with some substituted styrenes and ‘benzylidene acetones’ in MeCN and H₂O containing 10 mol‐% of MeCN are reported. The kinetic data were supported by theoretical calculations. The major products from styrenes were exo‐2‐aryl‐1,2,3,10b‐tetrahydropyrrolo[2,1‐a]phthalazine‐3,3‐dicarbonitriles 3 , and, from ‘benzylidene acetones’, 1‐endo,2‐exo‐2‐acetyl‐1‐aryl‐1,2,3,10b‐tetrahydropyrrolo[2,1‐a]phthalazine‐3,3‐dicarbonitriles 7 . There was no indication that the cycloadditon transition states were more polar in the aqueous environment than in MeCN.     

Water-selective spectral-spatial contrast-enhanced breast MRI for cancer detection in patients with extracapsular and injected free silicone

OBJECTIVE: This study investigates the use of contrast-enhanced, T1-weighted, water-selective spectral-spatial 3D gradient echo magnetic resonance imaging (MRI) with magnetization transfer (3DSSMT) for detecting breast cancer in patients with intraparenchymal silicone. CONCLUSION: Water-selective 3DSSMT provides superior fat and silicone suppression in patients with free silicone as compared with conventional fat saturation. It enables direct, high-quality, high-spatial-resolution, T1-weighted breast MRI of contrast enhancement without the need for subtraction processing and aids diagnosis of cancer in the breast with free silicone.     

Spin tagging for hyperpolarized ¹³C metabolic studies

In studies utilizing pre-polarized (13)C substrates to investigate metabolic activities in vivo, the metabolite signals observed in a region or a voxel contains a mixture of intracellular and extracellular components. This extracellular component arriving via perfusion may confound the measurements of metabolic flux or exchange rates. But if spin tagging is performed on the magnetization of the substrate, it may be possible to measure the signals of the metabolic products in the intracellular space that were derived from the tagged substrate spins locally. In this study, a spin tagging pulse sequence designed for acquiring data from spatially tagged longitudinal magnetization in hyperpolarized (13)C metabolic studies was presented and tested. Using a spectral-spatial RF pulse during the tagging preparation enabled the observation of metabolite signals derived exclusively from the tagged substrate in vivo.     

An Efficient Steric Controlled Photo-Fries Rearrangement in the Naphthalene Series

For the work on the synthesis of 2-acyl-5-methoxynaphthoquinones as tricyclic analogues of daunomycinone¹, we wanted to develop an efficient regioselective synthesis of 5-methoxy-2-acyl-1-naphthols without using Lewis acids. This requirement precluded the use of the thermal Fries but not the photo-Fries rearrangement. Although the mechanistic aspects of the photo reaction have received much study², the reaction has been little used preparatively³ because it usually gives poor yields of hydroxy ketones even when only one product is possible.     

High-performance liquid chromatographic analysis of biogenic amines in biological materials as o-phthalaldehyde derivatives.

A remarkably sensitive, simple and selective reversed-phase high-performance liquid chromatographic (HPLC) method has been developed, allowing, for the first time, the direct measurement of histamine, norepinephrine, octopamine, normetanephrine, dopamine, serotonin and tyramine in a single sample of plasma (2 ml), tissue (0.2 g), or urine. The biogenic amines were modified by pre-column derivatization with o-phthalaldehyde which stabilizes the molecules, aids in extraction, and improves HPLC detection at the nanogram level. To minimize losses during the sampling procedure a careful collection procedure was designed. We developed a simple sample cleanup in which the samples were thawed, neutralized with KOH, immediately derivatized, extracted into ethyl acetate (EtOAc) and then chromatographed by HPLC. The derivatives were stable in EtOAc for more then 24 h. Interfering amino acids were removed from the EtOAc by partitioning twice with Na2HPO4 buffer (pH 10.0). Complete separation was achieved in ca. 60--90 min on a muBondapak phenyl column using a stepwise gradient of acetonitrile and/or methanol-phosphate buffer (pH 5.1). A variable wavelength fluorometer with a 5-microliter flow-cell was used (excitation 340 nm; emission 480 nm). Linearity ranged from 200 pg to 50 ng onto the column. Precision (R.S.D.) for retention times was 1% and for derivatization and injection 2.5%. Recoveries of the seven biogenic amines from plasma spiked with 25 ng/ml averaged 70%, with a relative standard deviation of 6%. Separation studies were also done using a muBondapak C18 column. The effects of various eluents are presented. Gas-liquid chromatography was also investigated but lacked the sensitivity achieved by HPLC. The HPLC method is used routinely for the determination of biogenic amines in plasma from pigs with malignant hyperthemia and thermally stressed bovine. Significant differences in levels of biogenic amines were noted between stressed and non-stressed animals. Data on rat brain tissue samples were compared with the trihydroxyindole method and canine heart tissue was analyzed for ventricular norepinephrine and dopamine. Application of the method to urine from normal persons and a patient with a brain tumor has been demonstrated.     

Regioselectivity in intramolecular addition of allylsilanes to conjugated dienones

The intramolecular addition of allylsilanes to conjugated dienones shows a divergence of regioselectivity as a function of reagent and substrate structure. The creation of 5-5, 6-5, 5-7, and 6-7 bicyclic ring systems is reported.     

Testing membership in matroid polyhedra

Given a matroid M on E and a nonnegative real vector x=(x_j:j∈E), a fundamental problem is to determine whether x is in the convex hull P of (incidence vectors of) independent sets of M. An algorithm is described for solving this problem for which the amount of computation is bounded by a polynomial in |E|, independently of x, allowing as steps tests of independence in M and additions, subtractions, and comparisons of numbers. In case x ∈ P, the algorithm finds an explicit representation for x which has additional nice properties; in case x ? P it finds a most-violated inequality of the system defining P. The same technique is applied to the problem of finding a maximum component-sum vector in the intersection of two matroid polyhedra and a box.