Thursday, February 7, 2013, 7:00 PM (The LI-ACS Seminar)
Dr. John Regan (Queensborough Community College, CUNY)
Searching for Safer Anti-inflammatory Drugs
During the past fifty years the successful treatment of inflammatory diseases has relied on the use of glucocorticoid (GC) agonists such as dexamethasone and prednisolone. While effective in controlling asthma, rheumatoid arthritis, and other disorders, GC therapy is fraught with a number of severe side effects that hampers high dose and chronic administration. The probability of identifying a GC agonist with a better safety profile compared to existing therapies has substantially increased with newer understandings of the molecular mechanism of action. After an agonist enters a target cell and binds to the glucocorticoid hormone receptor (GR), the ligand-activated complex (GRC) translocates into the nucleus where direct and indirect functional pathways can be accessed. Acting directly, the GRC serves as an endogenous transcription factor by binding to specific DNA sequences and coactivator proteins, thereby initiating transcription of metabolic and endocrine genes. GRC-mediated transactivation of these genes is believed to contribute to the side effect profile of GC therapy. Acting indirectly, the GRC adopts a conformation with an affinity for transcription factors (e.g., NF-kB and AP-1). Subsequent binding to these transcription factors results in the inhibition of expression of pro-inflammatory cytokines such as TNF-α and IL-6. This process, known as transrepression, is thought to contribute, in part, to the anti-inflammatory component of GCs. Therefore, the search for GC agonists with a dissociated profile (greater transrepression than transactivation activity) has accelerated in recent years with an appreciation of the complex molecular pathways and the anticipation of an improved safety margin. We report on structure-activity-relationships (SAR) of a hybrid class of non-steroidal glucocorticoid agonists which combine essential pharmacophores of steroid A- and D-rings. Their biological assessment for nuclear receptor binding affinity, cellular activity of transrepression and transactivation, and anti-inflammatory properties will be discussed. In addition, the importance of optimum physicochemical properties for drug development will be highlighted.
Wednesday, March 13th, 2013, 1:00 PM
Dr. John A. Reffner (John Jay College of Criminal Justice, CUNY)
The Impact of Microspectroscopy on Forensic Investigations
Applying the scientific method and advanced technologies to analyze evidence in legal matters is the foundation of forensic science. Because of advances in infrared, Raman, ultraviolet and visible light micro-spectroscopy, molecular spectroscopy now plays a major role in forensic investigations. When microscopes became available accessories to Fourier transform spectrometer benches, the forensic community quickly recognized their advantages for microanalysis of trace evidence. In 1986, California equipped each of their 12 regional state forensic laboratories with FT-IR microscopes. Today, every major crime lab around the world has infrared microspectroscopy instrumentation. When the internal reflection objective was introduced in 1989, it was quickly put to work analyzing evidence. An advantage internal reflection is its ability to produce ATR spectra from the surface of thick samples. Paint transferred onto paint in a hit-run case could be analyzed directly without removing the transferred paint. More recently, diamond ATR objectives became available for analyzing glass and minerals which would damage earlier internal reflection elements. Using diamond extended the range of samples the forensic scientist could analyze by ATR.
The acceptance of molecular spectroscopy by forensic scientists increased with the availability of spectral data bases. Spectra of unknowns can be compared with standard reference materials in spectral libraries. This is of special interest in the analysis of powders related to homeland security issues. Field portable infrared or Raman spectrometers are used by first responders to identify "white powders". These units contain spectral libraries of hazardous chemical agents and are used for on-site, real-time analysis. The library searching software quickly suggests leads to assist the analyst in the identification of an unknown and its potential hazard. The advances in spectrometer design, solid-state lasers, low noise /high sensitive detectors, and improved notch filters have led to the development of new Raman spectrometers and micro-probes. These systems are being used in numerous forensic laboratories and show much promise for forensic applications. The future for molecular spectroscopy in forensic investigations is very exciting. Molecular spectroscopy provides rapid, reliable and reviewable record to aid investigators and the courts.
Wednesday, April 5, 2013, 1:00 PM
Prof. Dr. Markus Enders(Anorganisch-Chemisches Institut, Universität Heidelberg, Heidelberg, Germany)
Olefin Polymerisation with Organochromium Catalysts
Polyolefins like polypropylene or polyethylene are the most important synthetic polymers. Polyethylene is produced by a radical process, leading to low density polyethylene (LDPE), or by transition metal catalyzed processes leading to high density polyethylene (HDPE). The chromium based, heterogeneous Phillips catalyst is used for the bigger part of HDPE. In the past twenty years molecular chromium based catalysts have been developed which are able to polymerize ethylene with high activity, and the properties of the resulting polymers can be adjusted to a large extent. The seminar will summarize the present knowledge about molecular organochromium polymerization catalysts and will then switch to the research conducted in Heidelberg in this area. The molecular catalysts developed by us show preferential features which make them interesting for industrial application. In addition to that the molecular nature of the catalysts allows experimental and theoretical investigations of reaction mechanisms and kinetics so that a deeper understanding helps to systematically improve these catalytic systems and hence the resulting polymeric materials.