Extending molecular dynamics with dipolar NMR tensors as constraints to chiral phosphorus compounds.

Molecular dynamics with orientational constraints (MDOC) simulations use NMR parameters as tensorial constraints in the stereochemical analysis of small molecules. C-P Residual dipolar couplings-aided MDOC simulations of small phosphorus molecules determined the relative configurations of rigid molecules after including -couplings as additional constraints. However, flexible molecules remain a problem.

Exploring the impact of alignment media on RDC analysis of phosphorus-containing compounds: a molecular docking approach.

Residual dipolar couplings (RDCs) are employed in NMR analysis when conventional methods, such as -couplings and nuclear Overhauser effects (NOEs) fail. Low-energy (optimized) conformers are often used as input structures in RDC analysis programs. However, these low-energy structures do not necessarily resemble conformations found in anisotropic environments due to interactions with the alignment medium, especially if the analyte molecules are flexible.

Enantiodiscrimination of Inherently Chiral Thiacalixarenes by Residual Dipolar Couplings.

Inherently chiral compounds, such as calixarenes, are chiral due to a nonplanar three-dimensional (3D) structure. Determining their conformation is essential to understand their properties, with nuclear magnetic resonance (NMR) spectroscopy being one applicable method. Using alignment media to measure residual dipolar couplings (RDCs) to obtain structural information is advantageous when classical NMR parameters like the nuclear Overhauser effect (NOE) or -couplings fail.

P NMR parameters may facilitate the stereochemical analysis of phosphorus-containing compounds.

Conventional Nuclear Magnetic Resonance (NMR) analysis relies on H-H/C-H interactions. However, these interactions are sometimes insufficient for an accurate and precise NMR analysis. In this study, we show that P NMR parameters can provide critical structural insights into the stereochemistry of phosphorus-containing compounds.

Phosphate-Based Self-Immolative Linkers for the Delivery of Amine-Containing Drugs.

Amine-containing drugs often show poor pharmacological properties, but these disadvantages can be overcome by using a prodrug approach involving self-immolative linkers. Accordingly, we designed l-lactate linkers as ideal candidates for amine delivery. Furthermore, we designed linkers bearing two different cargos (aniline and phenol) for preferential amine cargo release within 15 min.

Phosphate-Based Self-Immolative Linkers for Tuneable Double Cargo Release.

Invited for the cover of this issue are Eliška Procházková, Ondřej Baszczyňski, and colleagues at IOCB (Prague) and Charles University (Prague). The image depicts phosphorus-based, double-cargo, self-immolative linkers capable of releasing both cargos sequentially after activation by light. Read the full text of the article at 10.

Phosphate-Based Self-Immolative Linkers for Tuneable Double Cargo Release.

Phosphorus-based self-immolative (SI) linkers offer a wide range of applications, such as smart materials and drug-delivery systems. Phosphorus SI linkers are ideal candidates for double-cargo delivery platforms because they have a higher valency than carbon. A series of substituted phosphate linkers was designed for releasing two phenolic cargos through SI followed by chemical hydrolysis.

Regioselective SAr reaction of the phenoxathiin-based thiacalixarene as a route to a novel macrocyclic skeleton.

The sulfonyl analogue of phenoxathiin-based thiacalix[4]arene, easily accessible from the parent thiacalix[4]arene, reacts with sodium alkoxides to yield a cleaved product representing a novel type of macrocyclic skeleton with a quasi-calixarene structure. As shown by comparison with other derivatives, the internal strain imposed by the heterocyclic moiety is a driving force of this SNAr reaction.