scholarly journals Nuclear magnetic resonance free ligand conformations and atomic resolution dynamics

2021 ◽  
Vol 2 (1) ◽  
pp. 489-498
Author(s):  
Amber Y. S. Balazs ◽  
Nichola L. Davies ◽  
David Longmire ◽  
Martin J. Packer ◽  
Elisabetta Chiarparin

Abstract. Knowledge of free ligand conformational preferences (energy minima) and conformational dynamics (rotational energy barriers) of small molecules in solution can guide drug design hypotheses and help rank ideas to bias syntheses towards more active compounds. Visualization of conformational exchange dynamics around torsion angles, by replica exchange with solute tempering molecular dynamics (REST-MD), gives results in agreement with high-resolution 1H nuclear magnetic resonance (NMR) spectra and complements free ligand conformational analyses. Rotational energy barriers around individual bonds are comparable between calculated and experimental values, making the in-silico method relevant to ranking prospective design ideas in drug discovery programs, particularly across a series of analogs. Prioritizing design ideas, based on calculations and analysis of measurements across a series, efficiently guides rational discovery towards the “right molecules” for effective medicines.

2021 ◽  
Author(s):  
Amber Y. S. Balazs ◽  
Nichola L. Davies ◽  
David Longmire ◽  
Martin J. Packer ◽  
Elisabetta Chiarparin

Abstract. Knowledge of free ligand conformational preferences (energy minima) and conformational dynamics (rotational energy barriers) of small molecules in solution can guide drug design hypotheses and help rank ideas to bias syntheses towards more active compounds. Visualization of conformational exchange dynamics around torsion angles, by replica-exchange with solute tempering molecular dynamics (REST-MD), gives results in agreement with high resolution 1H NMR spectra and complements free ligand conformational analyses. Rotational energy barriers around individual bonds are comparable between calculated and experimental values, making the in silico method relevant to ranking prospective design ideas in drug discovery programs, particularly across a series of analogues. Prioritizing design ideas, based on calculations and analysis of measurements across a series, efficiently guides rational discovery towards the right molecules for effective medicines.


1988 ◽  
Vol 110 (11) ◽  
pp. 3393-3396 ◽  
Author(s):  
Horst. Kessler ◽  
Christian. Griesinger ◽  
Joerg. Lautz ◽  
Arndt. Mueller ◽  
Wilfred F. Van Gunsteren ◽  
...  

2018 ◽  
Vol 2 (1) ◽  
pp. 23
Author(s):  
Juan Paúl Montalvo Herdoíza ◽  
Irene Monserrate Vergara Ibarra ◽  
Paula Salomé Macías Moreira ◽  
Jazmín Beatriz Anzules Guerra

  Se presenta un caso de quiste aracnoideo gigante paucisintomático, diagnosticado incidentalmente por Resonancia Magnética Nuclear (RMN) a los 5 años de edad, en el cual se evidenció una imagen hipodensa de gran tamaño ubicada en el lóbulo frontal derecho. El seguimiento, durante 17 años, no mostró ninguna alteración en las funciones cognitivas superiores dependientes del área afectada. Actualmente, la exploración neurológica del paciente es óptima. El paciente es un estudiante universitario brillante, lo que constituye un ejemplo contundente de plasticidad cerebral. Los quistes aracnoideos (QA) son tumoraciones benignas congénitas que forman una cavidad extracerebral, llena de líquido con características similares al líquido cefalorraquídeo (LCR), y recubierto por una membrana aracnoidea. La sintomatología por quistes aracnoideos dependen en gran manera del tamaño, y localización de la lesión. La clínica es variada incluyendo cefalea, deformidad craneana, déficit neurológico, convulsiones, entre otras manifestaciones, las cuales se presentan en más de la mitad de los casos. En ciertas lesiones intracraneales con efecto de masa se produce un fenómeno conocido como plasticidad cerebral que se define como la capacidad cerebral de evolucionar generando cambio estructurales y funcionales.   Palabras clave: plasticidad cerebral, quiste aracnoideo, resonancia magnética nuclear, neurología.   Abstract   This is a case of paucisymptomatic giant arachnoid cyst, incidentally diagnosed by Nuclear Magnetic Resonance (MRI) at 5 years of age, where a large hypodense image located in the right frontal lobe was evidenced, follow up for 17 years, did not show any alteration in the superior cognitive functions dependent on the affected area. Currently, the patient's neurological examination is optimal and he is a brilliant university student, which is a strong example of cerebral plasticity. The arcanoideos cysts (QA) are benign congenital tumors that form an ex-brain cavity, filled with liquid with characteristics similar to the cerebrospinal fluid (CSF), and covered by an arachnoid membrane. Symptoms due to arachnoid cysts depend greatly on the size, and localization of the lesion the clinic is varied including a headache, cranial deformity, neurological deficit, seizures, among other manifestations, which occur in more than half of the cases. In certain intracranial lesions with mass effect, a phenomenon known as cerebral plasticity is produced, is defined as the cerebral capacity to evolve, generating structural and functional changes.   Keywords: cerebral plasticity, arachnoid cyst, nuclear magnetic resonance, neurology.


2021 ◽  
Vol 12 (1) ◽  
pp. 56-59
Author(s):  
Mohammed Bahreldin Hussein ◽  
Muna Mahdi Mohammed ◽  
Abdalla Gobara ◽  
Asha Fadllallah Wady ◽  
Awad Salim Ibrahim Holy

Schiff bases are versatile ligands, synthesized via condensation of primary amines with carbonyl compounds. In this study, equimolar amounts of 4-imidazolecarboxaldehyde and thiosemicarbazide were combined and the Schiff base 4-imidazolecarboxaldehyde thiosemicarbazone was prepared as a new bidentate complexing agent. The synthesized ligand was reacted with palladium (II) and platinum (II) ions yielding air-stable complexes. For characterization purpose, infrared spectra, mass spectra, electronic spectra, thermal analysis, proton nuclear magnetic resonance and 13-carbon nuclear magnetic resonance spectra studies were carried out on the obtained complexes and ligand. The characterization data showed that the ligand acts as a bidentate coordinate to the metal ions through azomethine nitrogen and sulfur atoms. An in vitro antimicrobial investigation was also carried out for the free ligand and its metal complexes against four bacteria; Bacillus cereus, Staphylococcus aureus (Gram-positive), Escherichia coli and Salmonella typhimurium (Gram-negative) and one Fungi; Candida albicans, to assess their antimicrobial properties by disc diffusion technique. Antimicrobial activity of the prepared complexes showed higher activity than the free ligand.


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