Hasan Palandoken

Reductive dehydroxy coupling of 2-(hydroxymethyl)indenes to prepare ethano-bridged bis(2-indenyl) ansa-titanocenes

Hasan Palandoken et al. — Tue, 26 Apr 2011 11:29:20 PDT

New examples of ansa-titanocenes derived from 1,2-bis(2-indenyl)ethane have been prepared. The titanium-mediated reductive coupling of 2-(hydroxymethyl)indenes provided a convenient method for substrate dimerization. Alkyl substitution of the indene ring at C(3) improved the regioselectivity of the reductive coupling to provide the ethylene bis(2-indenyl)ansa-ligands in 29–62% yield.

Removal of Benzaldehyde from Methanol Using Alkoxyamine Functionalized Silica Gel

Dino Sulejmanovic et al. — Thu, 21 Apr 2011 15:11:28 PDT

Alkoxyamines (RONH₂) react readily with aldehydes and ketones to form stable oxime ethers, and, thus are expected to be excellent scavengers of these compounds. We installed alkoxyamines on silica gel surface to remove benzaldehyde from methanol. Silica gel was immersed in H₂O₂/H₂SO₄ solution to activate the surface. Activated silica gel was then reacted with 3-chloropropyltrichlorosilane. Displacement of the chloride with N-hydroxyphthalimide and subsequent treatment with hydrazine provided alkoxyamines on the surface of silica gel. The resulting silica gel surface with alkoxyamine functional groups was immersed in a 100 ppm benzaldehyde solution in methanol. After 24 h, the results showed 86.5 + 7.2 % removal of benzaldehyde from methanol.

Cariporide Prodrugs: Targeting Brain Cancer Cells through Sodium-Proton Exchange Inhibition

Jacob Vervynckt et al. — Thu, 21 Apr 2011 15:11:26 PDT

More than 200,000 people in the United States are diagnosed with a primary or metastatic brain tumor annually. The life expectancy for these individuals is approximately 9-12 months from the time of diagnosis. This poor prognosis is due to the ineffectiveness of existing therapies (i.e., chemotherapy and radiotherapy) against brain cancer, where the primary problem is the inability to differentiate cancer cells from healthy brain cells.

Relative to healthy brain tissue, the heightened metabolism of cancer cells increases their reliance on the ion transport proteins NHE (sodium-proton exchanger) and NCX (sodium-calcium exchanger). Inhibition of these proteins disrupts the intricate pH and ion balances within cancer cells to a much greater extent than in normal cells, and this leads to cancer cell death. In contrast, healthy brain cells are less affected by this targeted approach because they are far less reliant on NHE and NCX due to their normal (and lower) metabolic activity. Consequently, NHE and NCX are excellent molecular targets for a new, selective brain cancer therapy. Although potent NHE/NCX inhibitors are available, a fundamental impediment to the field is the delivery of these compounds to poorly vascularized tissues.

As part of our target-specific approach to treating brain cancer, we have synthesized analogs of cariporide, a potent (e.g., nanomolar IC50 activity) NHE inhibitor, to address the drug delivery challenge. The preparation and biological activities of our cariporide analogs will be discussed

Alkoxyamine Polymers: Versatile Materials for Surface Ligation Applications

Lindsey Hines et al. — Thu, 21 Apr 2011 15:11:25 PDT

Immobilization of biomolecules (i.e., proteins, carbohydrates), on polymeric surfaces has been an area of intense research. The resultant bioconjugates often display increased stability, bioavailability and activity. Our research program seeks to explore the utility of the alkoxyamine (RONH2) functional group in new materials as versatile ligating sites for the immobilization of various compounds.

The ease with which alkoxyamines (RONH2) condense with aldehydes or ketones has prompted their widespread use in labelling liposome, bacterial and mammalian cell surfaces as well as chemoselectively ligating small molecule ‘recognition elements' onto polyfunctional substrates. These condensation reactions proceed in aqueous media to afford the robust oxime ethers in near quantitative yields, making these conjugations ideal for a variety of applications. Thus, alkoxyamines are excellent ‘molecular anchors' to immobilize aldehyde/ketone compounds on a surface.

We have installed alkoxyamines on polymer surfaces to tether a variety of compounds through the covalent oxime ether bond to the polymer backbone. Our synthetic efforts towards these novel alkoxyamine polymers as well as initial aldehyde/ketone immobilization studies will be discussed.

The Effects of a Networked Data Acquisition System on Student Learning in General Chemistry Laboratories

Stuart C. Burris et al. — Thu, 21 Apr 2011 15:11:23 PDT

We have recently incorporated a networked data acquisition and analysis system into in our second semester general chemistry laboratories. Our investigation team has conducted a study to evaluate the effects of the networked data acquisition system on student performance on a Beer's Law laboratory. We focused on two specific phenomena: the effect of the networked data acquisition system on 1) student learning of specific content material and 2) student comfort level with laboratory work and data analysis. The study involved a networked data acquisition group (employing a UV-Vis spectrometer and colorimeters) and a control group (employing traditional, single wavelength spectrometers). Pre- and post-assessments were performed using written surveys, one-on-one student interviews, and lab practical tasks. Results from the study indicating changes in student baseline knowledge relating to Beer's Law and student comfort level in performing measurements and analysis will be presented.

The Effects of PC-Based Laboratories on Student Learning

Lester L. Pesterfield et al. — Thu, 21 Apr 2011 15:11:21 PDT

The Department of Chemistry at Western Kentucky University recently incorporated a net-worked MeasureNet data acquisition and analysis system into in the second semester General Chemistry laboratories. Our investigation team has conducted a study to evaluate the effects of the MeasureNet system on student learning and performance on a Beer's Law laboratory. We focused on two phenomena: the effect of the MeasureNet system on 1) student learning of specific content material and 2) student interest in chemistry and science in general. The study involved a MeasureNet system group (employing a UV-Vis spectrometer and colorimeters) and a control group (employing traditional Spectronic 20D instruments). Pre- and post-assessments were performed using written surveys, one-on-one student interviews and lab practical tasks. Results from the study indicating changes in student baseline knowledge relating to Beer's Law and student comfort level in performing measurements and analysis will be presented.

Progress Toward Cariporide Analogs for Sodium-Proton Exchange Inhibition

Jessica Moore et al. — Thu, 21 Apr 2011 15:11:19 PDT

The sodium proton exchanger (NHE) is particularly important in maintaining the intracellular pH in human heart and brain. Under anaerobic conditions (i.e., ischemia), a shift from oxidative to nonoxidative glycolysis occurs. The resultant decrease in the intracellular pH activates NHE, which increases the intracellular sodium, initiating the sequence of physiological events that lead to cell death. Thus, there has been great interest in the development of compounds that inhibit NHE. Indeed, potent NHE inhibitors are available. However, a fundamental impediment to the field is the delivery of these compounds to poorly vascularized tissues during the early phases of ischemia when NHE inhibition is most beneficial. We have synthesized analogs of cariporide, a potent (e.g., nanomolar IC50 activity) NHE inhibitor, to address these temporal and delivery challenges. The preparation and biological activities of our cariporide analogs will be discussed.

Dual Inhibition Of Sodium-Mediated Proton And Calcium Efflux Triggers Non-Apoptotic Cell Death In Malignant Gliomas

William Harley et al. — Tue, 19 Apr 2011 15:51:58 PDT

Malignant glioma cells maintain an elevated intracellular pH (pH_i) within hypoxic–ischemic tumormicroenvironments through persistent activation of sodium–proton transport (McLean et al., 2000). Amiloride has been reported to selectively kill human malignant glioma cell lines but not primary astrocytes (Hegde et al., 2004). While amiloride reduces pH_i of malignant gliomas by inhibiting isoform 1 of sodium–proton exchange (NHE1), direct acidification was shown to be cytostatic rather than cytotoxic. At cytotoxic concentrations, amiloride has multiple drug targets including inhibition of NHE1 and sodium–calciumexchange. Amiloride's glioma cytotoxicity can be explained, at least in part, by dual inhibition of NHE1 and of Na⁺- dependent calcium efflux by isoform 1.1 of the sodium–calcium exchanger (NCX1.1) , which increases [Ca²⁺]_i and initiates glioma cell demise. As a result of persistent NHE1 activity, cytosolic free levels of sodium ([Na⁺]i) in U87 and C6 glioma cells are elevated 3-fold, as compared with normal astrocytes. Basal cytosolic free calciumlevels ([Ca²⁺]i) also are increased 5-fold. 2′, 4′-dichlorobenzamil (DCB) inhibits the sodium-dependent calcium transporter (NCX1.1) much more potently than NHE1. DCB was employed in a concentration-dependent fashion in glioma cells to selectively inhibit the forwardmode of NCX1.1 at ≤1 μM, while dually inhibiting bothNHE1 and NCX1.1 at ≥20 μM. DCB (1 μM) was not cytotoxic to glioma cells,while DCB (20 μM) further increased basal elevated levels of [Ca²⁺]i in glioma cells thatwas followed by cell demise. Cariporide and SEA0400 are more selective inhibitors of NHE1 and NCX1.1 than amiloride or DCB, respectively. Individually, Cariporide and SEA0400 are not cytotoxic, but in combination induced glioma cell death. Like amiloride, the combination of Cariporide and SEA0400 produced glioma cell death in the absence of demonstrable caspase activation.

Process for the Preparation of Citalopram Intermediate

Aslam A. Malik et al. — Tue, 19 Apr 2011 15:51:56 PDT

The present invention provides, inter alia, a novel process for the preparation of Citalopram, a known antidepressant.

A Facile Synthesis of (tert-alkoxy)amines

Hasan Palandoken et al. — Tue, 19 Apr 2011 15:51:54 PDT

Tertiary alcohols react with stoichiometric BF₃·Et₂O and N-hydroxyphthalimide to yield N-alkoxyphthalimides. Subsequent hydrazinolyses afford the title compounds.

An Improved Synthesis Of 2-(Hydroxymethyl)Indene

Hasan Palandoken et al. — Tue, 19 Apr 2011 15:51:52 PDT

Clean, High-yield Preparation Of S,S- and R,S- Amino Acid Isosteres

Aslam A. Malik et al. — Tue, 19 Apr 2011 15:51:49 PDT

The present invention provides compounds and methods that can be used to convert the intermediate halomethyl ketones (HMKs), e.g., chloromethyl ketones, to the corresponding S,S- and R,S-diastereomers. More particularly, the present invention provides: (1) reduction methods; (2) inversion methods; and (3) methods involving the epoxidation of alkenes. Using the various methods of the present invention, the R,S-epoxide and the intermediary compounds can be prepared reliably, in high yields and in high purity.

Preparation of 2S,3S-N-Isobutyl-N-(2-hydroxy-3-amino-4-phenylbutyl)-p-nitrobenzenesulfonylamide hydrochloride and other derivatives of 2-hydroxy-1,3-diamines

Aslam A. Malik et al. — Tue, 19 Apr 2011 15:51:47 PDT

The present invention provides a new process for the preparation of 2S,3S-N-isobutyl-N-(2-hydroxy-3-amino-4phenylbutyl)- p-nitrobenzenesulfonylamide hydrochloride, wherein this compound is prepared directly from the chloromethylalcohol. Importantly, the process of the present invention results in higher yields of 2S,3S-N-isobutyl-N-(2hydroxy -3 -amino -4-phenylbutyl) -pnitrobenzenesulfonylamide hydrochloride without sacrificing its purity. The processes of the present invention can be used to prepare not only the 2S,3S-derivative, but also the 2R,3S-, 2S,2R- and the 2R,3R-derivatives.