Lithium Cuprate Coupling Reactions: Evaluation of Computational Methods for Determination of the Reaction Mechanisms

2010 ◽  
Vol 114 (14) ◽  
pp. 5005-5015 ◽  
Author(s):  
Lawrence M. Pratt ◽  
Stewart Voit ◽  
Binh Khanh Mai ◽  
BichLien H. Nguyen
2018 ◽  
Author(s):  
Yiming Zhao ◽  
Huy van Nguyen ◽  
Louise Male ◽  
Philip Craven ◽  
Benjamin R. Buckley ◽  
...  

<div>Twelve 1,5-disubtituted and fourteen 5-substituted 1,2,3-triazole derivatives bearing diaryl or dialkyl phosphines at the 5-position were synthesised and used as ligands for palladium-catalysed Suzuki-Miyaura cross-coupling reactions. Bulky substrates were tested, and lead-like product formation was demonstrated. The online tool SambVca 2.0 was used to assess steric parameters of ligands and preliminary buried volume determination using XRD obtained data in a small number of cases proved to be informative. Two modelling approaches were compared for the determination of</div><div>the buried volume of ligands where XRD data was not available. An approach with imposed steric restrictions was found to be superior in leading to buried volume determinations that closely correlate with observed reaction conversions. The online tool LLAMA was used to determine lead-likeness of potential Suzuki-Miyaura cross-coupling products, from which ten of the most lead-like were successfully synthesised. Thus, confirming these readily accessible triazole-containing phosphines as highly suitable ligands for reaction screening and optimisation in drug discovery campaigns.</div>


Author(s):  
John Ross ◽  
Igor Schreiber ◽  
Marcel O. Vlad

In a chemical system with many chemical species several questions can be asked: what species react with other species: in what temporal order: and with what results? These questions have been asked for over one hundred years about simple and complex chemical systems, and the answers constitute the macroscopic reaction mechanism. In Determination of Complex Reaction Mechanisms authors John Ross, Igor Schreiber, and Marcel Vlad present several systematic approaches for obtaining information on the causal connectivity of chemical species, on correlations of chemical species, on the reaction pathway, and on the reaction mechanism. Basic pulse theory is demonstrated and tested in an experiment on glycolysis. In a second approach, measurements on time series of concentrations are used to construct correlation functions and a theory is developed which shows that from these functions information may be inferred on the reaction pathway, the reaction mechanism, and the centers of control in that mechanism. A third approach is based on application of genetic algorithm methods to the study of the evolutionary development of a reaction mechanism, to the attainment given goals in a mechanism, and to the determination of a reaction mechanism and rate coefficients by comparison with experiment. Responses of non-linear systems to pulses or other perturbations are analyzed, and mechanisms of oscillatory reactions are presented in detail. The concluding chapters give an introduction to bioinformatics and statistical methods for determining reaction mechanisms.


ChemInform ◽  
2007 ◽  
Vol 38 (50) ◽  
Author(s):  
Giuseppe Bifulco ◽  
Paolo Dambruoso ◽  
Luigi Gomez-Paloma ◽  
Raffaele Riccio

2007 ◽  
Vol 4 (4) ◽  
pp. 496-501 ◽  
Author(s):  
M. Vamsi Krishna ◽  
D. Gowri Sankar

Simple, rapid and sensitive spectrophotometric procedures were developed for the analysis of Alfuzosin hydrochloride (AFZ) in pure form as well as in pharmaceutical formulations. The methods are based on the reaction of AFZ with nitrite in acid medium to form diazonium ion, which is coupled with ethoxyethylenemaleic ester (Method A) or ethylcyanoacetate (Method B) or acetyl acetone (method C) in basic medium to form azo dyes, showing absorption maxima at 440, 465 and 490 nm respectively. Beer’s law is obeyed in the concentration of 4-20 μg/mL of AFZ for methods A, B and 3-15 μg/mL of AFZ for method C. The molar absorptivity and sandell’s sensitivity of AFZ- ethoxyethylenemaleic ester, AFZ- ethylcyanoacetate and AFZ-acetyl acetone are1.90 × 104, 0.022; 1.93 × 104, 0.021 and 2.67 × 104L mole-1cm-1, 0.015 μg cm-2respectively. The optimum reaction conditions and other analytical parameters were evaluated. The methods were successfully applied to the determination of AFZ in pharmaceutical formulations.


Author(s):  
Matteo Pietraccini ◽  
Eloise Delon ◽  
Audrey Santandrea ◽  
Stéphanie Pacault ◽  
Pierre-Alexandre Glaude ◽  
...  

Author(s):  
John Ross ◽  
Igor Schreiber ◽  
Marcel O. Vlad

The topic of this chapter may seem like a digression from methods and approaches to reaction mechanisms, but it is not; it is an introduction to it. We worked on both topics for some time and there is a basic connection. Think of an electronic device and ask: how are the logic functions of this device determined? Electronic inputs (voltages and currents) are applied and outputs are measured. A truth table is constructed and from this table the logic functions of the device, and at times some of its components, may be inferred. The device is not subjected to the approach toward a chemical mechanism described in the previous chapter, of taking the device apart and testing its simplest components. (That may have to be done sometimes but is to be avoided if possible.) Can such an approach be applicable to chemical systems? We show this to be the case by discussing the implementation of logic and computational devices, both sequential machines such as a universal Turing machine (hand computers, laptops) and parallel machines, by means of macroscopic kinetics; by giving a brief comparison with neural networks; by showing the presence of such devices in chemical and biochemical reaction systems; and by presenting some confirming experiments. The next step is clear: if macroscopic chemical kinetics can carry out these electronic functions, then there are likely to be new approaches possible for the determination of complex reaction mechanisms, analogs of such determinations for electronic components. The discussion in the remainder of this chapter is devoted to illustrations of these topics; it can be skipped, except the last paragraph, without loss of continuity with chapter 5 and beyond. A neuron is either on or off depending on the signals it has received. A chemical neuron is a similar device.


2019 ◽  
Vol 4 (11) ◽  
Author(s):  
Marilia Valli ◽  
Helena Mannochio Russo ◽  
Alan Cesar Pilon ◽  
Meri Emili Ferreira Pinto ◽  
Nathalia B. Dias ◽  
...  

Abstract Technological advances have contributed to the evolution of the natural product chemistry and drug discovery programs. Recently, computational methods for nuclear magnetic resonance (NMR) and mass spectrometry (MS) have speeded up and facilitated the process of structural elucidation even in high complex biological samples. In this chapter, the current computational tools related to NMR and MS databases and spectral similarity networks, as well as their applications on dereplication and determination of biological biomarkers, are addressed.


2014 ◽  
Vol 16 (48) ◽  
pp. 26855-26863 ◽  
Author(s):  
Yasaman Jami Alahmadi ◽  
Ameneh Gholami ◽  
Travis D. Fridgen

Determination of the zwitterionic or canonical structure of proline in protonated and sodiated proline dimers.


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