Quantitative Quantum Mechanical Spectral Analysis (qQMSA) of Spectra of 1000+1 Chemical Shifts and Other Biological Systems

The quantitative analysis of urine offers the greatest challenge for quantitative NMR (qNMR) of biofluids - as for any analytical method. It has been proposed that nearly 200 metabolites could be analyzed from a standard 1D ¹H NMR spectrum [1] and it was also concluded that qNMR is the best method for urine profiling. The qNMR analysis is not straightforward and many approaches have been proposed for biofluids, but there is one, qQMSA [2], which is superior over the others, at least we believe so. qNMR analysis is based on the assumption that an NMR spectrum is a sum of the model spectra of its components [2]. In qQMSA the model spectra are prepared by fitting experimental spectra using the Quantum Mechanical (QM) theory, which is able to interpret even the smallest details of the spectra – but removing noise, impurity signals and other artefacts [2]. The QM models are field independent and pack effectively the spectral information. The QM models obtained from spectra measured at any field can be used as model for biofluid spectra measured at any other field. Simulation of our 212 metabolites and 1001 chemical shifts urine model takes < 0.5 sec/spectrum (if parallel simulation) and whole the analysis demands < 60 sec/spectrum – thus the speed is not anymore the bottle-neck in qQMSA. Our presentation describes essential features of qQMSA and the ChemAdder platform, developed specially for qQMSA, and reports the most recent results for the urine qQMSA. We also describe other novel applications, including metabolic flux analysis based on qQMSA of 2D HSQC spectra. See also http://chemadder.com.

[1] Bouatra, S. et al. The human urine metabolome. PLoS ONE 8, e73076, 2013. [2] Tiainen M, Soininen P, Laatikainen R, Quantitative Quantum Mechanical Spectra Analysis (qQMSA) of ¹H NMR Spectra of Complex Mixtures and Biofluids, J.Magn.Reson., 2014, 242, 67-78.