A fundamental view of enthalpyentropy compensation
(2014) In MedChemComm 5(9). p.13241336 Abstract
 In this paper, enthalpyentropy compensation (EEC) during the association of two molecules is studied by minimising model systems with molecular mechanics (MM) or quantum mechanics (QM), calculating translational, rotational, and vibrational contributions to the enthalpy and entropy with standard statisticalmechanics methods, using the rigidrotor harmonicoscillator approach. We start with simple twoatom models, for which dispersion and electrostatics can be studied separately, showing that there is no fundamental difference between dispersion, electrostatics, or even covalent interactions. All three types of interactions give rise to EEC and a saturation of T Delta S as Delta H becomes strongly negative. Next, homologous series of... (More)
 In this paper, enthalpyentropy compensation (EEC) during the association of two molecules is studied by minimising model systems with molecular mechanics (MM) or quantum mechanics (QM), calculating translational, rotational, and vibrational contributions to the enthalpy and entropy with standard statisticalmechanics methods, using the rigidrotor harmonicoscillator approach. We start with simple twoatom models, for which dispersion and electrostatics can be studied separately, showing that there is no fundamental difference between dispersion, electrostatics, or even covalent interactions. All three types of interactions give rise to EEC and a saturation of T Delta S as Delta H becomes strongly negative. Next, homologous series of complexes dominated either by dispersion or hydrogen bonds are studied. We see no qualitative difference between results obtained at the MM or QM level, and for all complexes except two very weak, EEC is observed, owing to the loss of translational and rotational entropy, typically counteracted by the vibrational entropy. Within homologous series, linear relations between T Delta S and Delta H with slopes of 0.11.7 are obtained with no clear difference between dispersive or hydrogenbonded systems (but similar to 0.01 for ionic and covalent interactions). These relations often reflect the increasing size of the complexes coming from the translational and rotational entropies, but at least for the hydrogenbonded complexes, it is significantly enhanced also by the vibrational entropy (which depends on the strength of the interaction). Thus, for homologous series of molecules with repeated interactions studied in vacuum, EEC is a rule. However, if water molecules are added, the relation is blurred and it can be predicted that for a real binding reaction in water solution, both enthalpyentropy compensation and anticompensation can be observed, depending on the detailed interaction of the two molecules with water before and after binding, further complicated by dynamic effects. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/record/4720082
 author
 Ryde, Ulf ^{LU}
 organization
 publishing date
 2014
 type
 Contribution to journal
 publication status
 published
 subject
 in
 MedChemComm
 volume
 5
 issue
 9
 pages
 1324  1336
 publisher
 Royal Society of Chemistry
 external identifiers

 wos:000341017700008
 scopus:84906539098
 ISSN
 20402511
 DOI
 10.1039/c4md00057a
 language
 English
 LU publication?
 yes
 id
 3762340801b64b7b89ba1d6e57c57891 (old id 4720082)
 date added to LUP
 20141031 09:04:07
 date last changed
 20171105 03:14:01
@article{3762340801b64b7b89ba1d6e57c57891, abstract = {In this paper, enthalpyentropy compensation (EEC) during the association of two molecules is studied by minimising model systems with molecular mechanics (MM) or quantum mechanics (QM), calculating translational, rotational, and vibrational contributions to the enthalpy and entropy with standard statisticalmechanics methods, using the rigidrotor harmonicoscillator approach. We start with simple twoatom models, for which dispersion and electrostatics can be studied separately, showing that there is no fundamental difference between dispersion, electrostatics, or even covalent interactions. All three types of interactions give rise to EEC and a saturation of T Delta S as Delta H becomes strongly negative. Next, homologous series of complexes dominated either by dispersion or hydrogen bonds are studied. We see no qualitative difference between results obtained at the MM or QM level, and for all complexes except two very weak, EEC is observed, owing to the loss of translational and rotational entropy, typically counteracted by the vibrational entropy. Within homologous series, linear relations between T Delta S and Delta H with slopes of 0.11.7 are obtained with no clear difference between dispersive or hydrogenbonded systems (but similar to 0.01 for ionic and covalent interactions). These relations often reflect the increasing size of the complexes coming from the translational and rotational entropies, but at least for the hydrogenbonded complexes, it is significantly enhanced also by the vibrational entropy (which depends on the strength of the interaction). Thus, for homologous series of molecules with repeated interactions studied in vacuum, EEC is a rule. However, if water molecules are added, the relation is blurred and it can be predicted that for a real binding reaction in water solution, both enthalpyentropy compensation and anticompensation can be observed, depending on the detailed interaction of the two molecules with water before and after binding, further complicated by dynamic effects.}, author = {Ryde, Ulf}, issn = {20402511}, language = {eng}, number = {9}, pages = {13241336}, publisher = {Royal Society of Chemistry}, series = {MedChemComm}, title = {A fundamental view of enthalpyentropy compensation}, url = {http://dx.doi.org/10.1039/c4md00057a}, volume = {5}, year = {2014}, }