Ferreira M. M. C., Kiralj R., "Relationships Between Crystal, Molecular, Physico-Chemical and Biological Properties of Alkylated 1H-Indole-3-Acetic Acids".  Caxambu, MG, 23-26/11/2003: 12° Simpósio Brasileiro de Química Teórica (XII SBQT) [12th Brazilian Symposium of Theoretical Chemistry], Livro de Resumos [Book of Abstracts], (2003) P151. Poster P151.

RELATIONSHIPS BETWEEN CRYSTAL, MOLECULAR
PHYSICO-CHEMICAL AND BIOLOGICAL PROPERTIES OF
ALKYLATED 1H-INDOLE-3-ACETIC ACID

Rudolf Kiralj (PQ), Márcia M. C. Ferreira (PQ),
rudolf@iqm.unicamp.br
Instituto de Química - UNICAMP, Campinas SP, 13084-971 Brazil.

Palavras-chave: alkylated 1H-indole-3-acetic acids, molecular mechanics, PLS

               1H-Indole-3-acetic acid  (IAA,  Scheme)  and  its  alkylated derivatives  are known  as
important plant-growth regulation hormones from auxin class. In general, relationships between
structure and activity for IAA derivatives have never been straightforward for a long time, mainly
due to the lack of a 3D structure of an auxin receptor,  intrinsic auxin properties,   and existence
of  heterogeneous   measurements   of   auxin  biological   properties   (plant-growth  promoting
activity).  Usually IAA auxins are limited to derivatives with small substituents at five substitution
positions at the indole ring  (2, 4, 5, 6  and  7).
               This work deals with IAA and its 10 alkylated derivatives:  2-Me-, 4-Me-, 5-Me-, 6-Me-,
7-Me-, 4-Et-, 5-Et-, 6-Et-, 5-Pr- and 5-Bu-IAA [1]. The following IAAs properties were studied: a)
crystal packing parameters based on crystal structures retrieved from the Cambridge Structural
Database  (unit cell volume  per  molecule,   crystal density,   average atomic volume,   packing
coefficients,    number   of   hydrogen   bonds,   total   number   of   intermolecular   interactions,
coordination number);   b)  molecular  properties  calculated  for  the  IAAs  based  on molecular
ormula  (relative molecular mass,  %carbon & hydrogen)  and based on geometry obtained from
crystal   structures  or    optimized    by    molecular    mechanics   MMFF94    (with   Montecarlo
conformational search) or ab initio B3LYP 6-31G** (ovality,  molecular volume,  Conolly surface
rea and volume,  torsion angles  T1:  C2-C3-C8-C9  and  T2: C3-C8-C9-O10);  c)  experimental
physico-chemical properties [1]  (octanol-water partition coefficient in logarithmic form,  average
proton  NMR  shift  for  indole  ring);  d)  biological  activity  on  Avena Sativa  L.  coleoptiles  [1]
(logarithmof  auxin molar concentration measured  at  the  half-maximum  coleoptile  elongation).
T1  and T2  and  Zn-O  bond lengths from  auxin binding protein 1  (ABP1)  [2] – IAA  complexes
optimized at MMFF94  level  were  also  used.   Correlations  including  all  the  properties  were
studied,  and partial least regression  models  (PLS)  were built  to  predict dependent  variables
(crystal density,  average  atomic volume,  packing  coefficient,  unit  cell  volume  per  molecule,
physico-chemical  and  biological  properties)   on   independent   ones   (all  other  descriptors).
              Conformational properties expressed  as  T1  and  T2  of  IAAs  in  vacuum, crystal and
complex  with  ABP1  show  significant  variations,   and  also  differences   in  correlations  with
dependent variables and in significance in PLS models.  Besides, there are notable  differences
in using different optimization  schemes  after  the conformational search.   Correlation  analysis
showed  important  linear  and  non-linear  correlations  between properties  of the same kind or
different kinds (crystal, molecular,  physico-chemical,  biological).  Parsimonius  PLS  regression
models  (Q > 0.70,  R > 0.85)  were built for most of the dependent variables.   As alkylated IAAs
make a homogeneous set of auxins,  the established relationships are reasonable.   (FAPESP)



Scheme. 1H-indole-3-acetic acid

[1] B. Nigovic et al., Acta Cryst. B56 (2000) 94.
[2] E.-J. Woo et al., EMBO J. 21 (2002) 2877.