The Structural and Analytical Chemistry Associate Program ( CAP)

is designed to develop methods for elucidation of molecular structures of bioactive phytochemicals in bioactive fractions provided by the ICBG Program. Those samples, which pass the primary and secondary screens and the dereplication process, will be sent to the structural chemistry/natural products (SC/NP) group at the University of Illinois at Urbana-Champaign for complete and comprehensive structural characterization.

The SC/NP group, under the direction of Dr. Lila, interfaces with the facilities of

the School of Chemical Sciences at the University of Illinois. These facilities are among the best and most extensive available, both in terms of equipment and personnel, and provide a comprehensive basis for the structural determination of biologically active compounds. Central to these facilities is the Molecular Spectroscopy Laboratory, which is home to seven modern superconducting NMR spectrometers, including three 500 MHz, a 600MHz and a 750 MHz instrument. Additionally, the Mass Spectrometry Center provides full service for all modern methods of organic mass spectrometry, with eight spectrometers available. MALDI, FAB, ESI and MS/MS experiments are routinely available. Four full-time and two part-time spectroscopists staff the facility. The combined use of NMR and Mass spectrometry forms the backbone of modern molecular structural analysis, and is so powerful that the structure of even large bio-molecules such as proteins can now be deduced. Samples provided under the ICBG program are expected, for the most part, to be smaller phytochemicals, such as alkaloids, phenolics and terpenoids, or other microbially-produced compounds all of which are readily amenable to MS/NMR analysis. The expertise, facilities and equipment of this group will be utilized in the proposed ICBG program.

Sample preparation is a critical step in the analysis of natural products. The sample preparation involves careful and scientific consideration of solvent systems, clean up procedures, isolation, and purification steps before final elucidation of the exact molecular structures. Phytochemicals can be easily degraded or inactivated during the routine but typically harsh and intrusive process of extraction and column-based fractionation.  In order to address the compound stability problem, Dr. Lila’s laboratory has adopted an effective and innovative rapid vacuum liquid chromatography strategy that permits the extraction and fractionation of large amounts of plant extract gently, rapidly, and with reduced amounts of solvent. Modern techniques in the isolation and purification process have also been adapted in Dr. Lila’s laboratory. Centrifugal Partition Chromatography (CPC) provides high-resolution, separation method that is uniquely applicable to sensitive (unstable) compounds, and allows quantitative recovery of the load sample. Once complete, the fractions are analyzed by HPLC, and the molecular structures of the active species determined using different spectroscopic analysis techniques. Mass Spectrometry and advanced NMR experiments will allow ab initio structural determination. By using two-dimensional COSY and HMQC NMR spectra of model compounds of known structure for ‘fingerprint’ analysis, active species can be characterized even in complicated mixtures. Moreover, some chemical reactions or semi-synthesis techniques are also conducted for chemical correlation and compound elucidation.