Rapid high-resolution four-dimensional NMR spectroscopy using the filter diagonalization method and its advantages for detailed structural elucidation of oligosaccharides

Four-dimensional nuclear magnetic resonance spectroscopy with high resolution of signals in the indirect dimensions is reported as an implementation of the filter diagonalization method (FDM). Using an oligosaccharide derivatized with 13C-labeled acetyl isotags, a four-dimensional constant-time pulse sequence was tailored for conjoint use with the FDM. Results demonstrate that high resolution in all dimensions can be achieved using a relatively short experimental time period (19 h), even though the spectrum is highly congested in the direct and all three indirect dimensions. The combined use of isotags, constant-time pulse sequences, and FDM permits rapid isolation of sugar ring proton spin systems in multiple dimensions and enables all endocyclic J-couplings to be simply measured, the key goal to assigning sugar stereochemistry and anomeric configuration. A general method for rapid, unambiguous elucidation of spin systems in oligosaccharides has been a long-sought goal of carbohydrate NMR, and isotags combined with the FDM now enable this to be easily performed. Additional general advantages of the FDM program for generating high-resolution 2D slices in any dimension from a 4D spectrum are emphasized.     

Progress on the two-dimensional filter diagonalization method. An efficient doubling scheme for two-dimensional constant-time NMR

An efficient way to treat two-dimensional (2D) constant-time (CT) NMR data using the filter diagonalization method (FDM) is presented. In this scheme a pair of N- and P-type data sets from a 2D CT NMR experiment are processed jointly by FDM as a single data set, twice as large, in which the signal effectively evolves in time for twice as long. This scheme is related to "mirror-image" linear prediction, but with the distinction that the data are directly used, without any preprocessing such as Fourier transformation along one dimension, or point-by-point reflection. As the signal has nearly perfect Lorentzian line shape in the CT dimension, it can be efficiently handled by the FDM approach. Applied to model and experimental signals, the scheme shows significant resolution improvement, and appears to tolerate noise reasonably well. Other complex aspects of multidimensional FDM are discussed and illustrated.     

Regularized resolvent transform for direct calculation of 45 degrees projections of 2D J spectra

The regularized resolvent transform (RRT) has been applied in a novel way to J-resolved spectra. This involves the direct calculation of the 45 degrees projection without constructing the 2D spectrum. The results show a significant resolution enhancement over that obtained by the 45 degrees projection of a 2D Fourier spectrum, even for much larger signals. In particular, RRT is able to resolve peaks that belong to different overlapping multiplets in a very crowded spectral region, where the conventional technique fails for any signal size. The resolving power of this method along with the significantly shorter signals required, make this method a powerful tool in spectral assignment.     

RRT: the regularized resolvent transform for high-resolution spectral estimation

A new numerical expression, called the regularized resolvent transform (RRT), is presented. RRT is a direct transformation of the truncated time-domain data into a frequency-domain spectrum and is suitable for high-resolution spectral estimation of multidimensional time signals. One of its forms, under the condition that the signal consists only of a finite sum of damped sinusoids, turns out to be equivalent to the exact infinite time discrete Fourier transformation. RRT naturally emerges from the filter diagonalization method, although no diagonalization is required. In RRT the spectrum at each frequency s is expressed in terms of the resolvent R(s)(-1) of a small data matrix R(s), that is constructed from the time signal. Generally, R is singular, which requires certain regularization. In particular, the Tikhonov regularization, R(-1) approximately [R(dagger)R + q(2)](-1)R(dagger) with regularization parameter q, appears to be computationally both efficient and very stable. Numerical implementation of RRT is very inexpensive because even for extremely large data sets the matrices involved are small. RRT is demonstrated using model 1D and experimental 2D NMR signals. Copyright 2000 Academic Press.     

Copper and iron interactions with angiotensin-converting enzyme inhibitors. A study by fast-atom bombardment tandem mass spectrometry

Fast atom bombardment, combined with high-energy collision-induced tandem mass spectrometry, has been used to investigate gas-phase metal-ion interactions with captopril, enalaprilat and lisinopril, all angiotensin-converting enzyme inhibitors.Suggestions for the location of metal-binding sites are presented. For captopril, metal binding occurs most likely at both the sulphur and the nitrogen atom. For enalaprilat and lisinopril, binding preferably occurs at the amine nitrogen. Copyright 1999 John Wiley & Sons, Ltd.