Organic NMR crystallography: enabling progress for applications to pharmaceuticals and plant cell walls.

The application of NMR crystallography to organic molecules is exemplified by two case studies. For the tosylate salt of the active pharmaceutical ingredient, Ritlectinib, solid-state NMR spectra are presented at a H Larmor frequency of 1 GHz and a magic-angle spinning (MAS) frequency of 60 kHz. Specifically, N-H heteronuclear multiple-quantum coherence (HMQC) and H-H double-quantum (DQ) single-quantum (SQ) correlation experiments are powerful probes of hydrogen bonding interactions.

Discovering the Solid-State Secrets of Lorlatinib by NMR Crystallography: To Hydrogen Bond or not to Hydrogen Bond.

Lorlatinib is an active pharmaceutical ingredient (API) used in the treatment of lung cancer. Here, an NMR crystallography analysis is presented whereby the single-crystal X-ray diffraction structure (CSD: 2205098) determination is complemented by multinuclear (H, C, /N, F) magic-angle spinning (MAS) solid-state NMR and gauge-including projector augmented wave (GIPAW) calculation of NMR chemical shifts. Lorlatinib crystallises in the P2 space group, with two distinct molecules in the asymmetric unit cell, Z' = 2.

Elucidation of microbial lignin degradation pathways using synthetic isotope-labelled lignin.

Pathways by which the biopolymer lignin is broken down by soil microbes could be used to engineer new biocatalytic routes from lignin to renewable chemicals, but are currently not fully understood. In order to probe these pathways, we have prepared synthetic lignins containing C at the sidechain β-carbon. Feeding of [β-C]-labelled DHP lignin to RHA1 has led to the incorporation of C label into metabolites oxalic acid, 4-hydroxyphenylacetic acid, and 4-hydroxy-3-methoxyphenylacetic acid, confirming that they are derived from lignin breakdown.

Exploring the Potential of Multinuclear Solid-State H, C, and Cl Magnetic Resonance To Characterize Static and Dynamic Disorder in Pharmaceutical Hydrochlorides.

Crystallographic disorder, whether static or dynamic, can be detrimental to the physical and chemical stability, ease of crystallization and dissolution rate of an active pharmaceutical ingredient. Disorder can result in a loss of manufacturing control leading to batch-to-batch variability and can lengthen the process of structural characterization. The range of NMR active nuclei makes solid-state NMR a unique technique for gaining nucleus-specific information about crystallographic disorder.

Combining X-ray and NMR Crystallography to Explore the Crystallographic Disorder in Salbutamol Oxalate.

Salbutamol is an active pharmaceutical ingredient commonly used to treat respiratory distress and is listed by the World Health Organization as an essential medicine. Here, we establish the crystal structure of its oxalate form, salbutamol oxalate, and explore the nature of its crystallographic disorder by combined X-ray crystallography and C cross-polarization (CP) magic-angle spinning (MAS) solid-state NMR. The *C-OH chiral center of salbutamol (note that the crystal structures are a racemic mixture of the two enantiomers of salbutamol) is disordered over two positions, and the -butyl group is rotating rapidly, as revealed by C solid-state NMR.

Evaluation of Alpha-Amylase Inhibitory, Antioxidant, and Antimicrobial Potential and Phytochemical Contents of L.

L. is a traditionally used medicinal plant. The present study was designed to explore the α-amylase inhibitory, antioxidant, and antimicrobial activities of L.

Lumbosacral Transitional Vertebrae In Patients Visiting Tertiary Care Hospital Of Khyber Pakhtukhwa: A Radiological Study.

Background: Lumbosacral transitional vertebra is a common anatomical variant of the spine that possibly is related to low back pain. The objective is to determine the frequency of Lumbosacral Transitional Vertebrae on lumbosacral radiographs in patients with low back pain visiting Neurosurgery OPD of Khyber Teaching Hospital Peshawar Khyber Pakhtunkhwa (KP).

Methods: This cross-sectional study was conducted on radiographs of lumbosacral spine in patients visiting for low back pain to the Neurosurgery OPD of Khyber Teaching Hospital Peshawar.

An Integrated Systems Biology and Network-Based Approaches to Identify Novel Biomarkers in Breast Cancer Cell Lines Using Gene Expression Data.

Breast cancer is the most common cause of death in women worldwide. Approximately 5%-10% of instances are attributed to mutations acquired from the parents. Therefore, it is highly recommended to design more potential drugs and drug targets to eradicate such complex diseases.

In silico T-cell and B-cell Epitope Based Vaccine Design Against Alphavirus Strain of Chikungunya.

Background: Chikungunya an arbovirus, is transmitted to humans by the bite of Aedes mosquito. The virus occurrences have been reported in Southeast Asian countries including Pakistan. Its symptoms include typical febrile illness and arthralgic syndrome.