ACD/1D NMR Expert
Technical Information
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ACD/1D NMR Expert is designed to process and analyze a set of NMR spectra. The main operations are:
Spectrum database creation
The most efficient method of database creation is to use the group macro feature to load any number of NMR spectra. The corresponding chemical structures can be attached as an SDfile or a set of molfiles. Another way is to create the database manually, using the Import option.
Any database having 96 records (which is the standard number for Varian automated run mode) can be treated as 96 combinatorial well plates. The database can contain several plates, including incomplete (for example 4 x 8 format) and 384-well plates. ACD/1D NMR Expert permits several different types of record arrangements in a well plate.
Verification in batch mode
The ACD/1D NMR Expert spectrum verification procedure checks how well each spectrum matches the structure for large batches of experimental spectra. First it calculates the NMR spectrum for the structure given, and then it compares the predicted spectrum against the experimental one. The program gives a Match Factor between 0 (poorest match) and 1 (best match) for each structure and spectrum pair. The match factor is produced automatically for all the structure-spectrum pairs in the well plate set.
In addition, the verification procedure quantifies the RMS of Assignment (overall measure of the agreement between chemical shifts) and Structure Purity (estimated percentage of the substance in the sample).
Prior to verification, manually define solvent peaks and dark regions that will identify possible impurities for a selected subset of the spectra or the entire database. You can also set the way in which the program handles exchangeable protons in 1H NMR calculation. In addition, you can specify the peak width and shape, and the number of points for a calculated peak in a spectrum.
Set the contributions of chemical shifts, integrals, and multiplicity information for the autoassignment to cover a full range of verification possibilities. For example, focus on comparing existing chemical shifts with predicted shifts, or ask for precise matches for all of the multiplet properties. The main parameters, analysis details, and results of the verification are stored in the calculation protocol with each database record.
The quality of the match factor is displayed by coloring the well plates. Red is usually used to indicate a poor match, yellow an ambiguous match, and green a good match. The match factor ranges and the number of regions can be customized depending on the user's preference.
Advanced Verification
The products of combinatorial synthesis are sometimes plagued by the substantial amount of starting materials present. In this case, the resultant match factor may be biased because of reagent and product spectra similarity. To improve the accuracy and selectivity of the verification, the reagent structure can be used. By comparing the reagent and supposed product structures, the reaction site is identified and protons in close proximity to it are identified. These atoms are taken with greater weight during match factor calculation, preventing false positives when the amount of starting materials is significant.
Often the supposed product structure is only one of several possible isomers. Sometimes spectra of isomers differ significantly enough to give false negatives if not accounted for. Given the reagent structure, it is now possible to check for E/Z isomers (only if double bond is forming during the chemical reaction). In these cases the program will automatically generate match factors for both E and Z isomers, allowing the user to decide the appropriate match.
The spectrum acceptance test, among other things, allows the user to determine if a large amount of unreacted starting material is in the sample. Quanalyst can be used to specify a unique region in the starting material and calculate a reagent conversion. Verification will use this information in the determination of match factors to prevent false positives. Alternatively, other variables can be measured and used to accept or reject the sample. These can include the signal to noise ratio, solvent peak height, sample pH, etc.
Quantitation procedure
Use Quanalyst to monitor a reaction's progress on a plate. Analyze the integral in user-defined regions of the spectra and generate reports in plate, tabular, diagram and multi-spectral formats. Perform a qualitative analysis for several spectral regions at a time or quantify ratios of components. Perform a qualitative analysis of your Combi NMR result.
Viewing and reporting the results
- Report values such as match factor, structure purity, and structural properties inside the colored wells on a plate.
- Report spectra and structures in customizable tables and export them into other applications (Microsoft Word, Excel, PowerPoint, etc.).
- Report particular spectral regions for a series of calculated and experimental spectra for visual comparison.
- Report qualitative analysis on a graph to expose trends, consistencies, etc.
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