1. Investigation of the efficiency and mechanism of gelation and degelation of three positional isomers of aminobenzoic acid Vimon Tantishaiyakul Prince of Songkla University 25 th FAPA CONGRESS 2014 Kota Kinabalu, Sabah, Malaysia, 9-12 October 2014 1

2. Objectives Mechanism/interactions/properties of supramolecular hydrogels – low-molecular-weight gelators (LMWGs) Model compounds melamine (M) three positional isomers of aminobenzoic acid (AB) 2 PSUPSU oABmABpAB

3. Methods Differential scanning calorimetry (DSC) Viscoelastic measurements Fourier transform infrared spectroscopy (FTIR) Hot-stage microscope powder X-ray diffraction (PXRD) scanning electron microscopy (SEM) Computational method 3

4. – energy needed to dissociate the H-bond is endothermic. an endothermic peak – indicated the transition from the gel to a sol. an exothermic peak – reflects the formation of a gel 4

5. – All samples were in the gel form at low temperature – All samples became a sol at a higher temperature – All showed the characteristics of a thermo-reversible gel – gel formation temperatures oAB/M and pAB/M were comparable mAB/M was the lowest 5

6. The  E values in order from the lowest to the highest are pAB/M < mAB/M < oAB/M The lower  E indicated stronger interactions between the M and AB. The optimized structures and relative energies (  E) of the most possible conformation for each 1:1 AB/M cluster and the H- bond information intermolecular H- bond interactions formed between a COOH group of AB and the NH2 group and N atom of M. pAB/M :  E = 0.00 kcal mol –1 mAB/M :  E = 0.87 kcal mol –1 oAB/M :  E = 1.66 kcal mol –1 6 Interaction between pAB and M stronger than mAB and M oAB and M

7. storage moduli (G’) were higher than loss moduli (G”) – Indicate the samples were gels G’ value : pAB/M > mAB/M > oAB/M strength of the gels : pAB/M > mAB/M > oAB/M Computational results (strong interaction) : pAB/M > mAB/M > oAB/M 7 G’ > G” Gel Beyond 74 ° C – some samples could not be measured – due to the melting of the samples which turned into non- viscous liquids. pAB/M: G’ > G” over this specified temperature range Temperature sweep measurements : heating from 25 to 74 ° C

8. consistent with the DSC analysis that showed the melting temperature to be about 80 ° C 8

9. consistent with the DSC analysis that showed the melting temperature to be about 78 ° C 9

10. DSC: mp  55◦C, comparable to rheological measurement mAB/M, was a stronger gel than the oAB/M mAB/M exhibited a lower degelation temperature than the oAB/M 10 FTIR + computational Method verify this phenomena

11. More than one C=O band for the oAB/M was observed Generally, carboxylic acids exits as a dimer and their C=O stretching vibrations are lower than those of the monomers or the normal C=O of ketone. The shift to a higher wavenumber of the C=O bands probably due to the existence of the acids in their monomer forms and these C=O groups may instead form weaker H-bonds with M compared to the strong H-bonds of the dimers. M showed NH : 3469, 3419 and 3330 cm −1 oAB showed NH: 3324 and 3239 cm −1 oAB showed OH: 3100–2400 cm −1 oAB showed C=O: 1661 cm −1 oAB/M, NH: 3469 and 3419 cm −1 of M oAB/M, C=O: 1699, 1680 cm -1 11

12. mAB prefers to exist in its zwitterionic form mAB/M gel, C=O 1691 cm -1 : mAB was changed from its zwitterionic form, mABz, to the uncharged form when it formed a gel via interacting with M. M showed NH : 3469, 3419 and 3330 cm −1 mAB, NH: No peak mAB, C=O: No peak mAB/M, NH: 3420, 3344 mAB/M, C=O: 1691 cm -1 shift to a higher wavenumber 12

13. conversion of the mAB from the uncharged form in the gel state to the zwitterionic form when the mAB/M gel was heated to about 60 ° C. This FTIR data strongly supported the phenomena observed by the DSC and rheological studies. mAB/M gel, warm to sol at about 60  C Dry, FTIR C=O at 1691 cm −1 disappeared. 13

14. zwitterionic form of mAB (mABz), the most possible structure of the 1:1 mABz/M cluster was more unstable than the 1:1 mAB/M cluster. The  E value of the mABz/M cluster was higher than that of the mAB/M by about 6 kcal mol −1. an inter-molecular COO−· · ·NH 2 H-bond of mABz/M was very weak. weak interaction, low degelation temperature The H-bond between the mAB and M decrease when the mAB was changed to its zwitterionic structure, causing a lower degelation temperature 14 mABzw/M:  E = 6.72 kcal mol -1 mAB/M:  E = 0.87 kcal mol -1 oAB/M :  E = 1.66 kcal mol –1

15. pAB/M, NH: no peak detected demonstrate the strong H-bonds between the pAB and M via the NH groups of both the M and pAB with other groups of each compound. interactions between the M and AB are sequence of pAB/M>mAB/M, oAB/M. interactions between M and ABs (FTIR) were in agreement with the rheological and DSC analyses that showed the same order of gel strength M showed NH : 3469, 3419 and 3330 cm −1 pAB showed NH: 3461 and 3363 cm −1 pAB showed OH: 3100–2400 cm −1 pAB showed C=O: 1667 cm −1 pAB/M, NH: no peak pAB/M, C=O: 1693 cm -1 shift to a higher wavenumber monomer 15

16. similar features : SEM & polarizing micrographs Features of each gel remained almost unchanged on drying. Each gel and xerogel showed different structures. – different isomers of AB may cause distinct supramolecular interactions with M and create diverse structures. 16 Polarizing optical micrographs gels SEM images Freeze-dried xerogels

17. PXRD xerogels All samples show crystalline peaks. PXRD patterns of each xerogel were different from each other. Each xerogel showed different PXRD patterns compared to those of the individual components. This indicated that there were intermolecular interactions between M and each AB. 17

18. Conclusion 18 Thermo-responsive based on low-molecular-weight gelators (LMWG) M & ABs were successfully generated. Gelation efficiency : pAB/M > mAB/M > oAB/M Gel properties: DSC, viscoelastic measurements Interactions: FTIR, computational method Useful to investigate other LMWG systems for pharmaceutical applications

19. Dr. Supaporn Dokmaisrijan Dr. Namon Hirun Samon Juntarapet 19 Acknowledgements Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program through Grant No PHD/0045/2552 the Nanotechnology Center (NANOTEC), NSTDA, Ministry of Science and Technology, Thailand, through its program of Center of Excellence Network

20. Colloids and Surfaces A: Physicochem. Eng. Aspects 446 (2014) 118–126

21. PSU At a Glance... 1st University in Southern Thailand, est. 1967 5 Campuses Hat Yai Trang Pattani Phuket Surat Thani 21

22. You are allocated 10 minutes for your presentation, and 5 minutes for Q & A. Laptop (Microsoft Office 2007) and LCD projector facilities will be provided. Please submit your presentation file (pendrive) to the secretariat to be loaded into the laptop when you register during the conference. 22

23. – energy needed to dissociate the H-bond is endothermic. an endothermic peak indicated the transition from the gel to a sol. an exothermic peak reflects the formation of a gel 23

24. All ab initio calculations were performed using the Gaussian03W program. The study began by the full geometry optimization of the M, oAB, mAB (both in the uncharged, and the zwitterionicforms,) and with pAB molecules at the MP2/6-311 ++G(2d,2p) calculations. The optimized structures of these molecules were further used to generate the trial structures of the AB/M clusters. Since the mole ratio of the AB and M in each AB/M cluster in the experimental method was 1:1, calculations of the 1:1 AB/Mclusters were performed 24