RT Book, Section
A1 Miller, Susan
A2 Renslo, Adam
SR Print(0)
ID 1124842587
T1 Acid-Base Chemistry of Organic Molecules
T2 The Organic Chemistry of Medicinal Agents
YR 2016
FD 2016
PB McGraw-Hill Education
PP New York, NY
SN 9780071794213
LK accesspharmacy.mhmedical.com/content.aspx?aid=1124842587
RD 2024/10/15
AB While  carbon  (C)  and  hydrogen  (H)  form  the  foundation  of  organic  molecules,  the  rich  diversity  and  specificity  of  interactions  between  biological  and  drug  molecules  arises  from  the  presence  of  heteroatoms  (N,  O,  S,  P,  halides)  when  they  combine  with  C  and  H  to  form  various  functional  groups.  One  property  of  many  heteroatom  containing  molecules  is  a  certain  acidity  or  basicity  at  physiological  conditions  that  can  contribute  to  the  reactivity  and  physiochemical  properties  of  the  molecule.  Although  drug  molecules  are  often  designed  to  have  little  or  no  chemical  reactivity  as  administered,  once  absorbed  they  are  metabolized  (i.e.,  undergo  chemical  conversions  catalyzed  by  the  enzymes  of  drug  metabolism)  to  give  products  with  new  functional  groups  having  enhanced  reactivity,  potentially  leading  to  adverse  side  effects.  In  addition  to  influencing  reactivity,  acid/base  properties  and  the  charge  state  of  a  drug  molecule  contribute  significantly  to  its  relative  solubility  in  water  (as  found  in  the  interior  of  cells  and  in  bodily  fluids)  versus  nonpolar  media  (as  found  in  the  lipid  membranes  of  cells).  This  differential  solubility  impacts  the  absorption  of  the  drug  and  hence  the  amount  that  needs  to  be  administered  to  achieve  the  desired  effect.  In  this  chapter,  we  review  the  principal  models  of  acid  and  base  behavior  and  discuss  the  relationship  of  structure  and  bonding  to  the  acidity  of  different  types  of  “X–H”  bonds  (C–H,  N–H,  O–H,  S–H)  and  the  basicity  of  the  lone  pairs  of  electrons  on  the  corresponding  “X”  atoms  (:N,  :O,  :S).