Fall 2008 Schedule

I have an open door policy, so please stop by.  I enjoy teaching and talking to students, so if there is something that is unclear from class or from your reading, let’s talk about it.  If you stop by and I am not available, please call or email me and we can arrange an appointment.
 

Classes

Fall 2008
Chem 121
Chem 121L

Spring 2008
Chem 123
Chem 321
Chem 356d

Research
My research interests combine the fields of inorganic chemistry and biochemistry.  I am currently working on two different research projects: 

Nickel Complexes as Functional Urease Mimics
I am fascinated by the way nature uses metals to accomplish a great number of things.  For instance, metals have catalytic roles (such as Zn²⁺ in carboxypeptidase A), structural roles (Ca²⁺ in calmodulin and Na⁺ and Mg²⁺ in DNA), electron-transfer roles (Fe²⁺/Fe³⁺ in cytochrome), and charge-transfer roles (sudden flux of Na⁺ and K⁺ to control nerve impulses), just to name a few.  These metals drastically increase the rate of reactions (while maintaining rather mild conditions) and make an organized structure of what could be a jumbled mess of polypeptides.  Studying the way metals function in biological complexes can provide insight to how to design and synthesize smaller molecules that can accomplish the same amazing feats! 

In particular, I am interested in the role of nickel in the enzyme urease.  Urease is an enzyme that is found in various bacteria, fungi and plants.  It catalyzes the hydrolysis of urea to yield ammonia and carbamate, which subsequently decomposes to yield an additional ammonia molecule and carbonic acid.  Urea does not readily hydrolyze--it has a half-life of 3.6 years in aqueous solutions at 38°C!  In contrast, urease accomplishes this hydrolysis 10¹⁴ times faster than the spontaneous decomposition.  Thus, the active site of urease makes an excellent target of study for the design of a functional model: a small molecule mimic of the active site that will catalyze amide hydrolysis.

The active site of urease contains two nickel ions that are separated by approximately 3.5 Å.  One nickel, Ni(1), has distorted trigonal bipyramidal geometry and is ligated by two histidine residues and a water molecule, in addition to bridging hydroxyl and carbamate groups.  The second nickel, Ni(2), has pseudooctahedral geometry with two histidine ligands, an aspartate ligand, a water molecule and the two bridging ligands.  The goal of this project is to design, synthesize and characterized nickel complexes as functional urease mimics.  To begin, we will synthesize Schiff base (imine) ligands which also incorporate oxygen-donor atoms.  These ligands will be designed such that they can bind two nickel ions in close proximity--one of the characteristics of the urease active site.  Nickel complexes of these ligands will then be tested for their ability to catalyze the hydrolysis of urease.

Electrochemical Immunoassay for Pollutant Detection
In agricultural areas where crops need protection from the weeds that would limit production of the desired produce, herbicides called triazines are used to control broadleaf weeds.  Atrazine belongs to this class of herbicides and is the most widely used herbicide in the US, with a domestic annual use of 76 million pounds (2002).  In the midwest, where atrazine is used to control broadleaf and grass weeds in crops such as corn, sugarcane, and sorghum, concentrations of atrazine along the field edge have been detected up to 250 ppb.  After spring application of treated cornfield, atrazine has been detected as high as 740 ppm.  Atrazine has also been found in rainwater more than 180 miles from the nearest point of application, due to its ability to travel on dust particles.  These levels are alarming when compared to the current guidelines of 3 ppb for atrazine in drinking water (EPA).  While no health effects have been found on humans thus far, some alarming results have been shown for amphibians.  At 40 ppb atrazine, frogs were found to have demasculinzed larynges and induced hermaphroditism (both significantly affecting the ability of the amphibians to successfully reproduce--it is believed that atrazine is an endocrine-disrupting contaminant).  Not surprisingly, atrazine seems to have a larger effect on amphibians than on humans (since they spend their lives in water, but the results are still worrisome. 

The current methods for the detection of atrazine include HPLC, GC, MS and immunoassays.  While the first three methods provide effective and reliable techniques for the determination of pollutants, each of them involves the use of technically demanding, expensive, large instruments.  Furthermore, some of these methods may require extensive pretreatment of the sample before a determination can be made.  On the other hand, immunoassays are based on the recognition of a particular molecule by an antibody.  Antibodies  are large glycoproteins that are produced in the blood to recognize and bind foreign invaders, singling them out for elimination by the body's immune defenses.  Because of the remarkable sensitivity and selectivity of antibodies to antigens, antibodies have been used in many applications, including testing for pregnancy, cancer, and heart disease; purifying drugs for use in therapy; and grouping blood types.  Immunoassays are analytical methods that use the specific antibody-antigen interaction for the determination of sample components.  Because of their highly specific binding, antibodies can bind antigens even in complex matrices such as blood, urine, and plasma, and therefore, the need to pretreat a sample to remove these addition components may not be necessary.

Though the antigen-antibody binding event is strong and specific, no obvious signal is produced upon a binding event.  There are several different methods of detection that can be used to signal that the binding event has occurred.  These methods include surface plasmon resonance, total internal reflection, piezoelectric oscillator, reflectometric interference spectroscopy, magnetic, photometric and fluorometric and electrochemical detection.  Electrochemical detection offers many advantages over some of the other methods, including speed, accuracy and precision of the measurement.  In addition, optically transparent samples are not required and electrochemical devices are capable of miniaturization. 

The purpose of this research project is to develop first a new electrochemical immunoassay, and later, an immunosensor, for the detection of atrazine.  In order to do this, atrazine molecules with be tagged with an electrochemically active group, such as ferrocene.  This ferrocene-atrazine conjugate will then compete for binding sites on the anti-atrazine antibody.  The amount of atrazine in the sample will be determined by highly sensitive electrochemical techniques, such as differential pulse voltammetry.

Helpful Links

Web elements--interactive periodic table and info on all of the elements  (printable periodic table)
Chemfinder--look up info on multitudes of chemical compounds
NSF-REU--research opportunities for undergraduates
Search the American Chemical Society journals
Emolecules--Look up information on chemical compounds using names, registration numbers, etc.
SDBS --look up ¹H and ¹³C NMR, IR spectra for many organic compounds
Named reactions database --alphabetical list of named organic reactions