Frequency-swept HSQC sequences for high-throughput NMR analysis.

This article describes new versions of the DEPT phase-edited heteronuclear single quantum correlation (HSQC) pulse sequence with sensitivity enhancement. The sequences incorporate frequency-swept carbon and proton pulses. The new experiments are inherently robust, well-suited for a high-throughput setting in which sample-to-sample variations may be ignored.

Frequency-swept HMQC sequences for high-throughput NMR analysis.

We describe here new versions of the DEPT phase-encoded HMQC experiment that offer robust performance and improved sensitivity. The new sequences rely on frequency-swept proton and carbon pulses to minimize signal losses from miscalibrated pulses while providing 'J compensation' to optimize the signal strength over a range of heteronuclear coupling constants. By including both proton and carbon-swept pulses, the new sequences also offer an additional signal gain of roughly 10% over well-calibrated hard-pulse experiments.

Automated structure verification based on a combination of 1D (1)H NMR and 2D (1)H - (13)C HSQC spectra.

A method for structure validation based on the simultaneous analysis of a 1D (1)H NMR and 2D (1)H - (13)C single-bond correlation spectrum such as HSQC or HMQC is presented here. When compared with the validation of a structure by a 1D (1)H NMR spectrum alone, the advantage of including a 2D HSQC spectrum in structure validation is that it adds not only the information of (13)C shifts, but also which proton shifts they are directly coupled to, and an indication of which methylene protons are diastereotopic. The lack of corresponding peaks in the 2D spectrum that appear in the 1D (1)H spectrum, also gives a clear picture of which protons are attached to heteroatoms.

An investigation of the absolute configuration of the potent histamine H3 receptor antagonist GT-2331 using vibrational circular dichroism.

GT-2331 [(+)-1] is one of the most potent members of a class of chiral drug substances used to regulate the synthesis and release of histamine by the histamine H3 receptor, and as such, is an important biomarker for pharmaceutical companies conducting research in this field. In addition to overall structural features, the bioactivity of this molecule has also been found to be highly dependent on absolute stereochemistry, making the reliable assignment of this property a necessity. X-ray diffraction studies have provided conflicting data, leaving its three-dimensional structure uncertain.

Optimization of pyrrolidinone based HIV protease inhibitors.

Optimization of P1-substituted pyrrolidinone based HIV protease inhibitors has yielded analogs with very potent antiviral activity.

Neuromuscular blocking activity and therapeutic potential of mixed-tetrahydroisoquinolinium halofumarates and halosuccinates in rhesus monkeys.

Structure-activity relationships in rhesus monkeys for a novel mixed-onium class of ultra-short-acting nondepolarizing tetrahydroisoquinolinium neuromuscular blockers (NMBs) are described. Bis-onium chlorofumarate 20a with (1R,2S)-benzyltetrahydroisoquinolinium groups was a potent lead compound (ED(95) = 0.079 mg/kg) with an ultra-short duration of NMB effect (7.