Project

Discipline

magic angle spinning; HR-MAS NMR; membrane; bilayer; porphyrin interaction; tissue; liver tissue; skeletal muscle; kidney; biopsy; metabonomics; pharmaceutical analysis; pharmaceutical emulsions; pathophysiology; crème

Lead
Lay summary
LeadHigh Resolution Magic Angle Spinning (HR-MAS) NMR Spectroscopy is a technique for obtaining highly resolved NMR-spectra of semi-solid liquid-like materials which under static conditions usually give rise to broad line spectra of low informative value. The HR-MAS probe is anticipated to be mainly used in three different fields: (a) in chemistry for the investigation of model membranes, (b) in medicine for the investigation of tissue probes, and (c) in pharmacy for the investigation of semi-solid pharmaceuticals.BackgroundHR-MAS NMR Spectroscopy is a technique used to narrow NMR lines by spinning the sample around a certain ("magic") angle of 54.7° thereby averaging anisotropic interactions close to zero. Thus, HR-MAS makes NMR spectroscopy applicable to semi-solid materials which under static conditions yield only poorly resolved NMR spectra with very broad lines. Even though well established, there has been a lack of accessibility to the HR-MAS technique within the Swiss university institutions so far. With this technique we will be able to study a broad variety of semi-solid samples like emulsions, liquid crystals, gels, or biological tissue samples. The main advantages of HR-MAS applied to semi-solid samples are (i) strong resolution and sensitivity enhancements, (ii) applicability of nearly all 1D and 2D solution HR-NMR techniques, and (iii) the possibility to measure samples directly in a non-destructive way without any preparation steps.AimsMainly three interdisciplinary projects will use the HR MAS technique: (a) The interactions of porphyrinic photosensitizers with model membranes are studied by NMR spectroscopy to enhance the understanding of the principles underlying photodynamic therapy and ultimately to contribute to improved drug design. NMR is a very powerful tool for obtaining site-specific information. With HR-MAS, large bilayer systems or even real cell suspensions can be applied as membrane models.(b) HR-MAS will be applied to different human tissue types (liver, skeletal muscle, and renal tissue) in three different sub-projects, all involving in vivo MRS/MRI. The HR-MAS data will be correlated to in vivo MR spectra and are expected to contribute significant insights into metabolic profiles. Thus, HR-MAS of intact tissues may help interpreting and guiding in vivo MRS and may ultimately improve non-invasive diagnosis and treatment strategies.(c) In collaboration with SWISSMEDIC, the potential of HR-MAS will be explored as new analytical tool for direct characterization of complex mixtures in form of semi-solid samples like pharmaceutical crèmes and salves without any preceding preparation or separation steps. HR-

Direct link to Lay Summary

Last update: 21.02.2013

Number	Title	Start	Funding scheme

This proposal aims at obtaining financial support for the purchase of a High Resolution Magic Angle Spinning (HR-MAS) probe to be implemented in the NMR lab of the Chemistry Department at the University of Bern. HR-MAS NMR Spectroscopy is a technique used to narrow NMR lines by spinning the sample around a certain (“magic”) angle of 54.7° thereby averaging anisotropic interactions close to zero. Thus, HR-MAS makes NMR spectroscopy applicable to semi-solid materials which under static conditions yield only poorly resolved NMR spectra with very broad lines. For the investigators of this proposal, the requested equipment opens new fields to NMR spectroscopic research neither covered by solid state nor conventional solution state NMR spectroscopy. Owing to the broad variety of samples falling into the application field of HR-MAS, e.g. emulsions, liquid crystals, gels, or biological tissue samples, a diversified interdisciplinary usership will be able to benefit from the HR-MAS probe. In view of the current countrywide lack of accessibility to the HR-MAS technique within the Swiss university institutions, the equipment will close this gap and will enable us to keep up with modern state-of-the-art technologies, explore new applications fields and extend our competences. The main advantages of HR-MAS applied to semi-solid samples are (i) strong resolution and sensitivity enhancements, (ii) applicability of nearly all 1D and 2D solution HR-NMR techniques important for deriving structural information even from complex mixtures, and (iii) the possibility to measure samples directly in a non-destructive way without any preparation steps.The requested HR-MAS probe is anticipated to be mainly used in three different fields: (a) in chemistry for the investigation of model membranes, (b) in medicine for the investigation of tissue probes, and (c) in pharmacy for the investigation of semi-solid pharmaceuticals. In particular, the following research projects will be involved using HR-MAS:(a) Our current research is focused on probing the interactions of porphyrinic photosensitizers with model membranes by NMR spectroscopy. The studies are aimed at enhancing the understanding of the principles underlying photodynamic therapy and ultimately at contributing to improved drug design. Previous own results have demonstrated that NMR, constituting a novel approach for probing porphyrin/membrane systems, is a very powerful tool for obtaining site-specific information. HR-MAS - as confirmed by our test in the BRUKER application lab - will add a further significant technical improvement in achieving the goals of these studies. With HR-MAS, the currently applied membrane models can be extended to more relevant large bilayer systems or even to real cell suspensions. At the same time, HR-MAS yields major resolution and sensitivity enhancements and reduces elaborate preparation steps of the samples.(b) HR-MAS will be applied to different human tissue types in three different sub-projects, all involving in vivo MRS/MRI. The HR-MAS data will be correlated to in vivo MR spectra and are expected to contribute significant insights into metabolic profiles. Thus, HR-MAS of intact tissues may help interpreting and guiding in vivo MRS and may ultimately improve non-invasive diagnosis and treatment strategies. In particular, liver tissue will be investigated in different liver diseases with fat accumulation to gain insights into the nature of lipids, skeletal muscle tissue will be probed for characterization of metabolically interesting intramyocellular lipids, and renal tissue to determine the regional distribution of metabolites. The studies will benefit from the great advantage that HR-MAS provides the possibility to obtain well resolved NMR spectra from intact tissue samples.(c) In collaboration with SWISSMEDIC, the potential of HR-MAS will be explored as new analytical tool for direct characterization of complex mixtures in form of semi-solid samples like pharmaceutical crèmes and salves without any preceding preparation or separation steps. Based on own preliminary very promising results HR-MAS is expected to contribute to significant methodological and economical improvements in pharmaceutical analysis.