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Anesthetic activity and the electrostatic potential (revisited)

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Abstract

A survey of the fascinating history of anesthetics and the many critical findings that have improved our understanding of anesthetic activity is followed by an expanded analysis of the electrostatic potentials of 27 molecules and two noble gases with anesthetic activities ranging from high to totally inactive. We again find that an intermediate value for the internal charge separation (polarity) Π appears to be an important factor in anesthetic activity. Other electrostatic potential features that favor high anesthetic activity include the presence of at least one strongly positive site on the molecule and regions of weakly to moderately negative electrostatic potential. For 14 molecules with consistent anesthetic activity data, we find a reasonable multivariable correlation that reflects the above features and also includes a measure of molecular size, reflecting the polarizability. The commonalities found in the electrostatic potential data for the active anesthetics suggest that anesthetics interact via their positive and/or negative sites in noncovalent reversible interactions with target sites, perhaps in brain proteins.

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Acknowledgements

This contribution is dedicated to Professor Peter Politzer on the occasion of his 80th birthday. ZP-IS and JSM each had the privilege of having Dr. Politzer as their Ph.D. advisor. It is appropriate that this paper touches on aspects of research involving electrostatic potential and molecular surfaces that spans nearly three decades, including their times as both students and research associates. ZP-IS, PGS, and JSM are grateful for having the opportunity to work on numerous projects with Peter over the years, and congratulate him on many years of dedication to science. We look forward to this continuing for at least another decade. JSM recalls a comment made by Peter’s father some years ago: “Peter has spent most of his career working on things he knows nothing about.” This is a compliment in disguise; there is always more to learn. Bob Murray, one of JSM’s sons, phrases this slightly differently: “Perhaps Dr. Politzer’s greatest contribution to chemistry and mankind is his innate ability to look, write, and speak like he knows exactly what is going on. Using this skill has allowed collaborations and contributions that would not have been possible otherwise, and will forever shape the way we view and understand theoretical physical chemistry.”

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Authors and Affiliations

  1. CleveProp, 1951 W. 26th Street, Suite 409, Cleveland, OH, 44113, USA

    Zenaida Peralta-Inga Shields & Jane S. Murray

  2. Department of Chemistry and Biochemistry, Wright State University, Dayton, OH, 45435, USA

    Paul G. Seybold

  3. Department of Chemistry, University of New Orleans, New Orleans, LA, 70148, USA

    Jane S. Murray

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  1. Zenaida Peralta-Inga Shields
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  2. Paul G. Seybold
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  3. Jane S. Murray
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Correspondence to Jane S. Murray.

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This paper belongs to Topical Collection P. Politzer 80th Birthday Festschrift

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Shields, Z.PI., Seybold, P.G. & Murray, J.S. Anesthetic activity and the electrostatic potential (revisited). J Mol Model 24, 19 (2018). https://doi.org/10.1007/s00894-017-3547-x

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  • DOI: https://doi.org/10.1007/s00894-017-3547-x

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