Thermo-responsive interaction between  -cyclodextrin and amphiphilic biopolymers.

1. Thermo-responsive interaction between -cyclodextrin and amphiphilic biopolymers. Here we will discuss how the cosolute -cyclodextrin and temperature affect the interactions in aqueous solutions of a hydrophobically modified polymer.

2. 15,4 Å 6,9 Å 7,9 Å Chemical structure The toroidal shape -Cyclodextrin (-CD)

3. -Cyclodextrin (-CD) • -cyclodextrin (-CD) is a cyclic starch oligomer consisting of 7 (-1,4)-linked -D-glucopyranose units. • The apolar nature of -CD cavities allow CDs to act as hosts for both nonpolar and polar guests. • Inclusion of hydrophobic moieties (C8 groups) that is adapted to the cavity size.

4. Structure of alginate and HM-alginate: The chemical structure units of alginate (M = mannuronic acid and G = guluronic acid); Molecular weight: 150 000 An anionic copolymer, comprised of -D-mannuronic acid (M-block) and (14)-linked -L-guluronic acid (G-block) units arranged in non-regular blockwise pattern of varying proportion of GG, MG and MM blocks.

5. Hydrophobic modification: The synthesis of C8 hydrophobically modified alginate was carried out using an aqueous carbodiimide reaction. The investigated sample contains 31 mol % of C8 groups.The length of the hydrophobic tails is about 7 Å.

6. Turbidity of -CD:

7. Temperature-induced crystallization of -CD • In aqueous solutions of -CD, a temperature decrease leads to the formation of crystallites and the solution becomes turbid. • During the crystallization process that occurs at low temperatures, CD molecules assume a herringbone-like arrangement where the cavity of one molecule is blocked on both sides by adjacent, symmetry-related -CD molecules (cage structure). • The crystalline structure is stabilized by hydrogen bonds and van der Waals interactions.

8. Turbidity of alginate and HM-alginate solutions in the presence of -CD

9. Turbidity of alginate solutions in the presence of -CD • The increase of cloudiness in solutions of alginate with decreasing temperature and increasing -CD concentration indicates interaction between alginate and -CD. • The rather modest change of turbidity is due to the fact that -CD clusters are distributed over the alginate network and serve as cross-linkers.

10. Turbidity of HM-alginate solutions in the presence of -CD • The more drastic increase of the turbidity in solutions of HM-alginate with decreasing temperature and increasing -CD concentration is because of the formation of crystallites in the bulk. • Due to steric hidrance, -CD clusters are not active in the cross-linking of the network. • The decrease of the turbidity at the highest temperature is due to the encapsulation of hydrophobic tails.

11. Comparison of the relative turbidity for the alginate (2 wt %)/-CD/D2O and HM-alginate (2 wt %)/-CD/D2O systems

12. Effects of -CD concentration and temperature on the shear rate dependence of the relative viscosity

13. Effects of -CD concentration and temperature on the relative viscosity for alginate solutions • For the alginate/-CD system we observe a gradually more pronounced upturn of the relative viscosity at low shear rates as the temperature is lowered and the -CD concentration is increased. • The cosolutes forms clusters or crystallites that act as cross-linker of the alginate chains. • The junction zones formed through the interaction with -CD clusters, are disrupted at high shear rates.

14. Effects of -CD concentration and temperature on the relative viscosity for HM-alginate solutions • For the HM-alginate/-CD system we observe a strong decrease of the relative viscosity at low shear rates as the temperature is raised and the -CD concentration is increased. • The -CD molecules encapsulate the hydrophobic tails and thereby suppress the associations. • The HM-alginate network is disrupted at high shear rates.

15. Effects of -CD concentration and temperature on the relative zero-shear viscosity

16. Effects of -CD concentration and temperature in alginate solutions • No viscosity enhancement is observed at -CD concentrations up to 8 mmolal, because the aggregates are too small to cross-link the polymer chains. • At higher -CD levels and low temperatures, the cosolute aggregates grow and are sufficiently large to cross-link the chains and a strong viscosity enhancement is observed.

17. Effects of -CD concentration and temperature in HM-alginate solutions • In the absence of -CD or low -CD concentrations the viscosity rises moderately with increasing temperature, because the increased mobility of the chains activate several hydrophobic groups for intermolecular associations. • Steric hindrance prevent cross-linking of the network. • At high concentration of -CD and elevated temperature, the hydrophobic tails are encapsulated and the hydrophobic associations are suppressed and this results in low viscosity.

18. Effects of -CD concentration and temperature on the deactivation of polymer hydrophobic sites Model: (Karlson et al. Carbohydrate polymers 2002, 50, 219.) • Based on the Langmuir adsorption model. • The -CD molecules bind to the hydrophobic tails of the polymer chains with a complex formation constant K. • The viscosity enhancement is considered to originate from associations via the polymer hydrophobic moieties (effect of entanglement is neglected).

19. 0 and  are the zero-shear viscosity without -CD and in excess of -CD  is the fraction of occupied binding sites B is the concentration of polymer hydrophobic tails c-CD is the total concentration of -CD

20. Effects of -CD concentration and temperature on the fraction of occupied binding sites () High levels of -CD addition and elevated temperature promote the decoupling of hydrophobic interactions. More efficient complex formation between the hydrophobic tails and -CD at higher temperatures.

21. Deactivation of hydrophobic groups is promoted by higher temperature and increasing -CD concentration. Cross-linking of alginate chains at low temperatures and high -CD concentration.

22. Low temperature Formation of crystallites High conc. of -CD Schematic illustrations of alginate/-CD and HM-alginate/-CD interactions Alginate/-CD interactions and formation of crystallites In HM-alginate solutions, the large amount of hydrophobic groups prevent cross-linking due to steric hindrance.

23. Elevated temperature: + HM-alginate/-CD interactions and deactivation of hydrophobic tails. Low temperature:

24. Interactions between poly(-cyclodextrin) and HM-alginate. (C. Amiel et al. Macromolecules 2005, 38, 5243) Properties of poly(-cyclodextrin). • Poly(-cyclodextrin) is a copolymer synthesized by polycondensation with epichlorohydrin (EP) and this induces the formation of poly-tails and poly-bridges. • The polymer has a branched architecture where -CD molecules are modified by poly(2-hydroxypropyl)ether sequences of different lengths, possessing a free end or acting as a bridge between several CDs. • A compact structure with Mw=160 000; RG = 55 Å and Mw/Mn = 1.9. -CD content is 59 wt %.

25. Chemical structure of poly(-CD) and a schematic illustration of the compact structure A branched and compact structure, which can form bridges between different polymer chains

26. Rheological results Dilute mixtures of HM-alginate (0.5 wt %) and poly(-cyclodextrin) at a fixed temperature Zero-shear viscosity of the HM-alginate solution

27. Formation of interbridges between HM-alginate chains and poly(-cyclodextrin) • Dilute mixtures of HM-alginate (0.5 wt %) and poly(-cyclodextrin) at a fixed temperature. • Addition of poly(-cyclodextrin) to HM-alginate solutions generates interpolymer bridges and the viscosity increases. • Optimal strength is achieved when all hydrophobic sites for interpolymer bridging have been occupied.

28. Effect of temperature on the viscosity

29. Effect of temperature on the viscosity of HM-alginate/poly(-cyclodextrin) • A temperature increase promotes enhanced mobility of the polymer chains, and this reduces the tendency to form interpolymer connections with poly(-CD). • Due to the rather weak interpolymer associations, shear-thinning and disruption of the network occurs at fairly low shear rates.

30. Effect of temperature on the viscosity

31. Effect of temperature on shear-thinning and shear-thickening in HM-alginate/poly(-CD) mixtures. • The general trend of the viscosity curves is shear thinning at low and high shear rates, and the shear-thickening behavior (peak) at intermediate shear rates. • The viscosity peak is more pronounced as the temperature rises. • The reason for this is that augmented motions of polymer chains and cosolute molecules facilitate the shear-induced orientation and extension of the chains in the bridging process.

32. Addition of poly(-CD) Increased conc. of poly(-CD) Schematic illustration of the HM-alginate-poly(-cyclodextrin) interaction Addition of poly(-CD) leads to the formation of bridges between HM-alginate chains and this process continues until these sites have been occupied.

34. Conclusions • In -CD solutions without polymer, the cloud point increases with the -CD concentration. • High level of -CD and a low temperature promote the formation of large-scale aggregates or crystallites in solutions of HM-alginate. • Cross-linking of alginate chains at high concentrations of -CD and low temperatures. • In HM-alginate solutions, elevated temperature and high levels of -CD addition favor deactivation of hydrophobic tails.

35. The -CD concentration and temperature effects on the viscosity could be rationalized in a simple model, based on the Langmuir adsorption approach. • Addition of poly(-CD) to dilute solutions of HM-alginate leads to association through bridging of polymer chains. • A temperature increase gives rise to a lower viscosity and debridging of polymer chains.