The chromatographic study of complexation of functionalized calix[4,8]arenes with aromatic aldehydes

Aim. To study the Host-Guest complexation of octakis(diphenoxyphosphoryloxy)-tetramethylcalix[4]resorcinarene (PRA), 5,17-bis(N-tolyl-iminomethyl)-25,27-dipropoxycalix[4]arene (IC4A), 5,11,17,23-tetrakis(diisopropoxyphosphonyl)25,26,27,28-tetra-propoxycalix[4]arene (PC4A) and oktаkis(diethoxyphosphoryloxy)-tert-butylcalix[8]аrene (PC8A) with benzaldehyde, salicylaldehyde, p-anisaldehyde, and veratraldehyde by RP HPLC and molecular modeling methods. Results and discussion. The stability constants of Host-Guest complexes (КА = 57 М-1 – 1649 М-1) strongly depend on the calixarene structure and the aromatic aldehyde nature. The enhancement of the complexing properties of calixarenes is observed in the row of PRA < IC4A < PC4A < PC8A. The volume of the calixarene molecular cavity plays the most important role in binding of aldehydes. Experimental part. The stability constants of calixarene complexes with aldehydes were determined by RP HPLC method in acetonitrile-water (80 : 20, v/v) solution. The RP HPLC analysis was performed using a LiChrosorb RP-18 column. Molecular modeling of calixarene complexes was carried out using a Hyper Chem 8.0 program. Conclusions. The Host-Guest complexation data can be used as a useful tool in design of calixarene based sensor devices for determination of the aromatic aldehydes in air or preparation of chromatographic phases for analysis of aldehydes in solutions.

Since the aromatic aldehydes are widely used as starting materials or aromatic ingredients in pharmaceutical and cosmetics industry [18,19], the Host-Guest complexation data can be used as a useful tool in design of calixarene based sensor devices for determination of the aromatic aldehydes in air or preparation of chromatographic phases for analysis of compounds in solutions.

Results and discussion
Complexation of the calixarenes with aldehydes was studied in the acetonitrile-water solution by the RP HPLC method using the approach previously developed [20,21].The stability constants of calixarene complexes were calculated from the dependence of the aldehyde retention factor on the concentration of calixarenes in the mobile phase.
The calixarene additives to the mobile phase decrease the retention factors k' of aldehydes 1-4 due to formation of the Host-Guest inclusion complexes.The linear plots of 1/k'νs the calixarene concentration (Fig. 1-4) indicates formation of the Host-Guest supramolecular complexes with stoichiometry of 1 : 1 and allows using the equation ( 1) for calculation of their stability constants К А : whеre k 0 ' і k' -are capacity factors of the aldehyde molecule determined in the absence and the presence of the calixarene in the mobile phase.
The К А values and free Gibbs energies ∆G of the calixarene -aldehyde complexes are presented in Таble.
As can be seen from Table , the stability constants (К А = 57 М -1 -1649 М -1 ) strongly depend on the calixarene structure and the aromatic aldehyde nature.The enhancement of the complexing properties of calixarenes is observed in the row of PRA < IC4A < PC4A < PC8A.The volume of the calixarene molecular cavity plays the most important role in binding of aldehydes.PC8A exceeds PRA, IC4A and PC4A by 11-23 times for benzaldehyde, 6-15 times for salicylic aldehyde, 3-8 times for p-anisaldehyde, and 7-15 times for veratraldehyde complexation.It should be noted that the stability constant of the IC4A -benzaldehyde 1 complex (K A = 146 M -1 ) is close to those of the cyclophane -benzaldehyde complex (K A = 120 М -1 ) described in [22].
The calixarene Host-Guest complexes can be stabilized by hydrogen bonds, Van der Waals, π-π, C-H-.π, and hydrophobic interactions.The role of the hydrophobic interaction is confirmed by the linear dependences of the binding constants K A on the log P of aldehydes (Fig. 5).
The intermolecular hydrogen bonds between the Host and Guest molecules are clearly manifested in the energy minimized structures of the IC4A, PC4A, PC8A complexes with salicylaldehyde (Fig. 6).In the IC4A complex, the molecule of salicylaldehyde is included into the molecular cavity of the calixarene.In this case, the aldehyde hydroxyl group forms a hydrogen bond with the OH group oxygen atom on the lower rim of the macrocycle (O-H···O distance 2.84 Ǻ).
As it is shown on Fig. 7, the experimental free Gibbs energies ∆G of calixarene complexes (Table ) well correlate with relative energies ∆∆E of these complexes calculated by the molecular modeling method.

Molecular modeling
Molecular modeling of calixarene complexes was carried out using a Hyper Chem 8.0 program in the force field (PM3) [30].The structures were calculated by the semi-empirical method.The RMS (standard deviation of the word root mean square) gradient was equal to 0.01 kcal/A mol.

Conclusions
Calix [4]arenes functionalized with two N-tolyliminomethyl groups or four diisopropoxyphosphonyl groups at the upper rim, calix [8]arene functionalized with eight diisopropoxyphosphoryl groups at the lower rim, and calix [4]resorcinarene functionalized with eight diphenoxyphosphoryl groups at the upper rim form the Host-Guest inclusion complexes with the aromatic aldehydes in acetonitrile-water solutions.The stability constants of the complexes (К А = 57 М -1 -1649 М -1 ) strongly depend on the calixarene structure and the aromatic aldehyde nature.The enhancement of the complexing properties of calixarenes is observed in the row: PRA < IC4A < PC4A < PC8A.The Host-Guest complexation data can be used as a useful tool in design of calixarene based sensor devices for determination vapors of aldehydes in air or preparation of chromatographic phases for the analysis of aldehydes in solutions.
Conflict of interests: authors have no conflict of interests to declare.

Fig. 6 .
Fig. 6.The energy minimized structures of the Host-Guest complexes of salicylaldehyde with: IC4A (a), PC4A (b) and PC8A (c).Hydrogen bonds are shown as dotted lines

Fig. 7 .
Fig. 7. Correlation of experimental values of free Gibbs energies ∆G of the calixarene complexes with relative energies ∆∆Е of these complexes calculated by the molecular modeling method