Broadband homodecoupled NMR spectroscopy with enhanced sensitivity.

A new type of broadband homodecoupling technique is described, which is based on the original version of the Zangger-Sterk experiment, but results in a spectrum with higher sensitivity. The homodecoupling is performed by a combination of selective and non-selective 180° RF pulses in the presence of weak rectangular pulsed field gradients in a pseudo 2D experiment. The proposed experiment uses a fast pulsing approach to increase the signal-to-noise ratio per unit time.

Broadband homodecoupled heteronuclear multiple bond correlation spectroscopy.

A general concept for removing proton-proton scalar J couplings in 2D NMR spectroscopy is proposed. The idea is based on introducing an additional J resolved dimension into the pulse sequence of a conventional 2D experiment to design a pseudo 3D NMR experiment. The practical demonstration is exemplified on the widely used gradient coherence selected heteronuclear long-range correlation spectroscopy (HMBC).

Experimental access to HSQC spectra decoupled in all frequency dimensions.

A new operator called RESET "Reducing nuclEar Spin multiplicitiEs to singuleTs" is presented to acquire broadband proton decoupled proton spectra in one and two dimensions. Basically, the homonuclear decoupling is achieved through the application of bilinear rotation pulses and delays. A [BIRD](r,x) pulse building block is used to selectively invert all proton magnetization remotely attached to (13)C isotopes, which is equivalent to a scalar J decoupling of the protons directly attached to (13)C from all other protons in the spin system.

An alternative approach for recording of multidimensional NMR data based on frequency dependent folding mechanism.

A new scheme for obtaining HSQC spectra with improved resolution or in a shorter time called SHARC (Shaped Arrayed data aCquisition protocol) is proposed, which uses region selective RF pulses and allows the sweep width to be adjusted individually for each region. It thus bypasses the problems with the Nyquist theorem associated with other method suggested for this purpose. Assignment of the cross-peaks to their respective region is achieved by manipulating the phases of the RF pulses and/or their frequencies.

Tetrahydroisoquinoline-3-carboxylate based matrix-metalloproteinase inhibitors: design, synthesis and structure-activity relationship.

The design, synthesis and structure-activity relationship (SAR) of a series of nonpeptidic 2-arylsulfonyl-1,2,3,4-tetrahydro-isoquinoline-3-carboxylates and-hydroxamates as inhibitors of the matrix metalloproteinase human neutrophil collagenase (MMP-8) is described here. Based on available X-ray structures of MMP-8/inhibitor complexes, our structure-based design strategy was directed to complement major protein-ligand interaction regions mainly in the S1' hydrophobic specificity pocket close to the catalytic zinc ion. Here, the rigid 1,2,3,4-tetrahydroisoquinoline scaffold (Tic) provides ideal geometry to combine hydroxamates and carboxylates as typical zinc complexing functionalities, with a broad variety of S1' directed mono- and biaryl substituents consisting of aromatic rings perfectly accommodated within this more hydrophobic region of the MMP-8 inhibitor binding site.