PMID- 24460383
OWN - NLM
STAT- MEDLINE
DCOM- 20141023
LR  - 20231110
IS  - 1549-960X (Electronic)
IS  - 1549-9596 (Print)
IS  - 1549-9596 (Linking)
VI  - 54
IP  - 2
DP  - 2014 Feb 24
TI  - Theoretical prediction of hydrogen-bond basicity pKBHX using quantum chemical 
      topology descriptors.
PG  - 553-61
LID - 10.1021/ci400657c [doi]
AB  - Hydrogen bonding plays an important role in the interaction of biological 
      molecules and their local environment. Hydrogen-bond strengths have been 
      described in terms of basicities by several different scales. The pKBHX scale has 
      been developed with the interests of medicinal chemists in mind. The scale uses 
      equilibrium constants of acid...base complexes to describe basicity and is 
      therefore linked to Gibbs free energy. Site specific data for polyfunctional 
      bases are also available. The pKBHX scale applies to all hydrogen-bond donors 
      (HBDs) where the HBD functional group is either OH, NH, or NH+. It has been found 
      that pKBHX can be described in terms of a descriptor defined by quantum chemical 
      topology, DeltaE(H), which is the change in atomic energy of the hydrogen atom upon 
      complexation. Essentially the computed energy of the HBD hydrogen atom correlates 
      with a set of 41 HBAs for five common HBDs, water (r2=0.96), methanol (r2=0.95), 
      4-fluorophenol (r2=0.91), serine (r2=0.93), and methylamine (r2=0.97). The 
      connection between experiment and computation was strengthened with the finding 
      that there is no relationship between DeltaE(H) and pKBHX when hydrogen fluoride was 
      used as the HBD. Using the methanol model, pKBHX predictions were made for an 
      external set of bases yielding r2=0.90. Furthermore, the basicities of 
      polyfunctional bases correlate with DeltaE(H), giving r2=0.93. This model is 
      promising for the future of computation in fragment-based drug design. Not only 
      has a model been established that links computation to experiment, but the model 
      may also be extrapolated to predict external experimental pKBHX values.
FAU - Green, Anthony J
AU  - Green AJ
AD  - Manchester Institute of Biotechnology (MIB) , 131 Princess Street, Manchester 
      M1 7DN, Great Britain.
FAU - Popelier, Paul L A
AU  - Popelier PL
LA  - eng
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140204
PL  - United States
TA  - J Chem Inf Model
JT  - Journal of chemical information and modeling
JID - 101230060
RN  - 0 (Organic Chemicals)
RN  - 059QF0KO0R (Water)
SB  - IM
MH  - Entropy
MH  - Hydrogen Bonding
MH  - Hydrogen-Ion Concentration
MH  - *Models, Molecular
MH  - Molecular Conformation
MH  - Organic Chemicals/*chemistry
MH  - *Quantum Theory
MH  - Water/chemistry
PMC - PMC4004274
EDAT- 2014/01/28 06:00
MHDA- 2014/10/24 06:00
PMCR- 2014/04/29
CRDT- 2014/01/28 06:00
PHST- 2014/01/28 06:00 [entrez]
PHST- 2014/01/28 06:00 [pubmed]
PHST- 2014/10/24 06:00 [medline]
PHST- 2014/04/29 00:00 [pmc-release]
AID - 10.1021/ci400657c [doi]
PST - ppublish
SO  - J Chem Inf Model. 2014 Feb 24;54(2):553-61. doi: 10.1021/ci400657c. Epub 2014 Feb 
      4.