Kiralj R., Ferreira. M. M. C., "A Simple Quantitative Structure-Property Relationship (QSPR) Approach to Stability Constants of Metal-Crown Ether Complexes in Methanol". Águas de Lindóia, SP, Brazil, 10-15/09/2006: 10th International Conference on Chemometrics in Analytical Chemistry (CAC-2006, CAC-X), Book of Abstracts (2006) P081. Poster 081.

10th International Conference on Chemometrics in Analytical Chemistry P081

A Simple QuantitativeStructure-Property Relationship (QSPR)
Approach to Stability Constants of Metal-Crown Ether Complexes
in Methanol

Rudolf Kiralj*, Márcia M. C. Ferreira   rudolf@iqm.unicamp.br

Laboratório de Quimiometria Teórica e Aplicada, Instituto de Química, Universidade Estadual
de Campinas, Campinas – SP, 13083-970 BRAZIL

Keywords: crown ethers, PLS regression, Cambridge Structural Database
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   The discovery of crown ethers in late  60's  as effective metal cation carriers (ionophores) opened a new
area in metal chemistry.   Ionophores  are  used  today  for  complexation  (in  homogeneous  solutions)  or
solvent extraction  of  alkali,  earth alkaline,  transition  and  other  metals.  The  search  for  desired  metal
selectivity  of  crown ethers and other ionophores in  one-  or  two-phase  liquid systems is interesting from
the  point  of  view  of  analytical chemistry,   because  related  analytical techniques  are employed in vital,
agricultural,  biological  and  industrial  processes.   These  search  efforts are still predominantly empirical.
This  work  is  a  theoretical  approach  (QSPR:   Quantitative Structure-Property Relationships)  to  model
stability constants of complexes formed by cations Ag⁺, Na⁺, K⁺, Mg²⁺, Ca²⁺, Sr²⁺ and Ba²⁺ and four crown
ethers  in  methanol:    18-crown-6    (18C6),    dibenzo-18-crown-6    (DB18C6),   dicyclohexyl-18-crown-6
(DCY18C6), and dibenzopyridino-18-crown-6 (DBPY18C6).
   Measured stability constants  for  the  28  complexes were from literature¹. Various atomic descriptors for
metals and ligand descriptors  for  the crown ethers were collected from  literature or were calculated  from
the  crystal  structures  of  crown  ether  and  metal  complexes  retrieved  from  the  Cambridge  Structural
Database (CSD). Five descriptors were manually selected for the final QSPR model:   cation radius,  metal
electron affinity, mean metal-O,N  bond length (from CSD median values), and two more steric descriptors.
These two descriptors included the metal radii and metal-O,N  bond lengths,  macrocycle size  (average O-
O,N  diametral distances  from  the CSD median values),  and  O,N  van der Waals radii.  Autoscaled  data
were  then  used  in  the  Partial  Least  Squares  (PLS)  regression   to  predict  metal-macrocycle  binding
constants in log form.   The dataset was also used in exploratory analysis  (Principal Component Analysis -
PCA and Hierarchical Cluster Analysis - HCA).
   The descriptors  are  moderately  correlated with the stability constants  (absolute correlation coefficients
are 0.44-0.75).  Three  principal  components  (PCs)  were  used  for  the  PLS  model (99.2%  of  the total
variance), resulting  in  acceptable  QSPR  statistics:   Q = 0.730,  R = 0.830, SEV = 0.46,  SEC = 0.40,  7
samples with relative error greater than  10%  (10-16%).   The  regression vector  and correlograms  show
relationships that can be well interpreted chemically.   Higher complex stability is  related to larger ions that
are  tightly bound  to  the  macrocyle  and probably  to  the solvent,  ions  that  are displaced from the  O,N
macrocycle plane due to their size  and  higher coordination number  (more than 6),  and  ions  with higher
electron affinity (good electron acceptors in coordinative bonds).  Small variations in the stability constants
originates from the differences in crown ether structures.  More rigid  DB18C6  and  DCY18C6  are basket-
shaped and somewhat poorer binders. More flexible 18C6 and  DCY18C6  (with cyclohexyl units acting as
additional  arcs)  are  better  metal  binders.   Ag-DBY18C6   is   an  exception   due   to  electronic  effects
accounting for pyridine-Ag bond. Crystal structures for the CSD and simple molecular modeling were used
to visualize stereoelectronic relationships in the complexes and other related structures.
   Clustering of the samples is almost identical in  PCA  (3 PCs: 99.6% of the total variance) and HCA, and
agrees  with  previously noted trends.   There are seven metal clusters at  similarity index  0.85  (complete
linkage was used), among which that for  Mg  is isolated,  and  Ba-K  and  Ca-Na  clusters form a group at
similarity index around  0.75.  PC1 is mainly related to the cation size,  whilst PC2 distinguishes well metal
groups  i.e.  discriminates  alkali  (Na, K)  from   alkaline  earth  (Mg, Ca, Sr, Ba)   and   other  (Ag)  metals.
   The  presented  approach  to   model  metal-crown  ether   stability  constants  was  based  on  available
structural  data  in  literature  and  structural  databases  and  not  on  descriptors from molecular modeling.
This methodology can be expanded  to other  metal-macrocycle  systems  and used in practice as the  first-
aid QSPR that provides reasonable interpretation of the obtained results.
 

Acknowledgment: FAPESP
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References

¹ Zolgharnein J.; Tahmasebi H.; Habibi M.; Amani S. J. Inclus. Phenom. Macrocyc. Chem. 2004, 49, 231-234.