The accurate estimation of S-O bond dissociation enthalpies (BDE) of sulfoxides by computational chemistry methods has been a significant challenge. One of the primary causes for this challenge is the well-established requirement of including high-exponent d functions in the sulfur basis set for accurate energies. Unfortunately, even when high-exponent d functions were included in Pople-style basis sets, the relative strength of experimentally determined S-O BDE was incorrectly predicted. The aug-cc-pV(n+d)Z basis sets developed by Dunning include an additional high-exponent d function on sulfur. Thus, it was expected that the aug-cc-pV(n+d)Z basis sets would improve the prediction of sulfoxide S-O BDE. This study presents the S-O BDE predicted by B3LYP, CCSD, CCSD(T), M05-2X, M06-2X, and MP2 combined with aug-cc-pV(n+d)Z, aug-cc-pVnZ, and Pople-style basis sets. The accuracy of these predictions was determined by comparing the computationally predicted values to the experimentally determined S-O BDE. Values within experimental error were obtained for dialkyl sulfoxides when the S-O BDEs were estimated using an isodesmic oxygen transfer reaction at the M06-2X/aug-cc-pV(T+d)Z level of theory. However, the S-O BDE of divinyl sulfoxide was overestimated by this method.
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J Chem Inf Model
January 2024
Material and Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877, United States.
Autoxidation of drugs and drug-like molecules is a major concern in the development of safe and effective therapeutics. Because active pharmaceutical ingredients (APIs) that contain sulfur atoms can form sulfoxides under oxidative stress, predicting oxidative susceptibilities within an organic molecule can have a major impact in accelerating the compound's stability assessment. For investigation of a sulfur atom's oxidative stability, density functional theory (DFT) methods were applied to accurately predict S-O estimated bond dissociation enthalpies (BDEs) of sulfoxides.
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Department of Medicine, University of Washington, Box 356422, 1959 NE Pacific Street, Room AA522, Seattle, WA 98195, USA.
Severe congenital neutropenia (SCN) is a life-threatening marrow failure disorder, usually caused by heterozygous mutations in . Potential genetic treatment strategies include biallelic knockout or gene correction via homology-directed repair (HDR). Such strategies, however, involve the potential loss of the essential function of the normal allele product or limited coverage of diverse monogenic mutations within the patient population, respectively.
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December 2011
School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Compounds containing heteroatom-heteroatom bonds are regarded as "undesirable" in drug discovery projects possibly due to their inherent fragility, i.e., low bond dissociation energies (BDEs).
View Article and Find Full Text PDFJ Phys Chem A
April 2011
Department of Chemistry, Saint Louis University, 3501 Laclede Avenue, Saint Louis, Missouri 63103, United States.
J Org Chem
March 2003
Instituto de Química Física Rocasolano, CSIC, Serrano 119, 28006 Madrid, Spain.
A rotating-bomb combustion calorimeter specifically designed for the study of sulfur-containing compounds [J. Chem. Thermodyn.
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