TY - JOUR
T1 - Use of the harmonic mean to the determination of dissociation constants of stereoisomeric mixtures of biologically active compounds
AU - Guevara-Salazar, J. Alberto
AU - Quintana-Zavala, Delia
AU - Jiménez-Vázquez, Hugo A.
AU - Trujillo-Ferrara, José
N1 - Publisher Copyright:
© 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Herein we introduce the derivation of a mathematical expression to evaluate the dissociation constant of a mixture of stereoisomers in equal amounts (KdMIX), when the corresponding dissociation constants (Kd) or medium response (MR50) of the pure stereoisomers are known; the final equation takes the form of the harmonic mean. In order to validate the equation, we carried out a bibliographic search of experimental data of enantiomeric molecules with biological activity, considering the Kd's or MR50's of the isolated enantiomers as well as that of the racemate. The comparisons between the experimental dissociation constants of the mixtures (KdEXP or MR50EXP) and the calculated values (KdMIX or MR50MIX) were consistent; the similarity between these values is supported through statistical analyses of group comparison and simple linear correlation. The equation we obtained, which corresponds to the harmonic mean, was used to predict the values of KdMIX (or MR50MIX) or Kd (or MR50) in systems when only two of the experimental values are known: either the dissociation constants of both enantiomers or the Kd (or MR50) of one of the enantiomers and dissociation constant of the racemate.
AB - Herein we introduce the derivation of a mathematical expression to evaluate the dissociation constant of a mixture of stereoisomers in equal amounts (KdMIX), when the corresponding dissociation constants (Kd) or medium response (MR50) of the pure stereoisomers are known; the final equation takes the form of the harmonic mean. In order to validate the equation, we carried out a bibliographic search of experimental data of enantiomeric molecules with biological activity, considering the Kd's or MR50's of the isolated enantiomers as well as that of the racemate. The comparisons between the experimental dissociation constants of the mixtures (KdEXP or MR50EXP) and the calculated values (KdMIX or MR50MIX) were consistent; the similarity between these values is supported through statistical analyses of group comparison and simple linear correlation. The equation we obtained, which corresponds to the harmonic mean, was used to predict the values of KdMIX (or MR50MIX) or Kd (or MR50) in systems when only two of the experimental values are known: either the dissociation constants of both enantiomers or the Kd (or MR50) of one of the enantiomers and dissociation constant of the racemate.
KW - Dissociation constants
KW - Enantiomers
KW - Harmonic mean
KW - Medium
KW - Racemate
KW - Response
UR - http://www.scopus.com/inward/record.url?scp=84913583644&partnerID=8YFLogxK
U2 - 10.3109/14756366.2013.866656
DO - 10.3109/14756366.2013.866656
M3 - Artículo
SN - 1475-6366
VL - 29
SP - 884
EP - 894
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
IS - 6
ER -