Polymeric Surfactant P84/Polyoxometalate α-PW₁₂O₄₀³⁻—A Model System to Investigate the Interplay between Chaotropic and Hydrophobic Effects

Round 1

Reviewer 1 Report

This work by Schmid et al. discusses the interaction of the commercial polyoxometallate PW12O40 with a PEO-PPO-PEO (pluronic) block copolymer. The authors carry out phase-diagram characterization for systems containing water, the copolymer, and the POM. After establishing the relevant equilibria and the effects of temperature, the authors characterize the micelles that are formed by NMR, SAXS and SANS. These powerful methods prove that in the monomer (premicellar) state of the block copolymer the POM interacts with the hydrophobic PPO units. Polymer micelles are forming depending on the concentration and temperature, and these micelles become elongated at higher temperatures. The POM now interacts more strongly with the PEO units that constitute the corona of the micelles. The conclusion is that both ion (super)chaotropicity (responsible for its interfacial activity) and the hydrophobic effect (responsible for the formation of polymeric micelles) determine the dominant structures in this complex system.

POMs are interesting since they are very large, yet sticky ions because of their small charge density. The present work provides one more look into their interesting interfacial properties. The work is well executed and the results novel and interesting enough; the SAXS and SANS modeling is sound and the combination of these two methods (one does not see it very much these days!) is quite illuminating. The topic of the investigation is interesting and timely. I therefore suggest that the paper may be accepted and published with very minor revisions.

 

• The decision to investigate this particular system is not very well explained. It sounds strange to say that, because we know that the POM interacts with PEO and PPO, we will examine how it interacts with a PEO-PPO copolymer.
• Why assume that the POM comes with 7 water molecules? Apart from previous experience, have the authors done any TGA on the commercial POM?
• The so-called “Langmuir fit” to the cloud-point concentration graph is an unfortunate procedure introduced by Cremer in a 2005 paper in JACS. Since then, this type of fitting has been used by several authors, but there is no theoretical justification for the application of Langmuir isotherms to cloud point curves and no clear way to explain/ understand the binding constants obtained from these fits.
• Line 212 is incomprehensible.
• The last sentence of the paper (lines 316-317) is not fully justified. It is not clear that the balance of hydrophobic and chaotropic effects will have a decisive effect “in the assembly of hierarchical systems” as the authors state. In fact, I have found the ending of the paper rather abrupt. One would expect to see a statement where to go from this point.

Author Response

Referee 1:

This work by Schmid et al. discusses the interaction of the commercial polyoxometallate PW12O40 with a PEO-PPO-PEO (pluronic) block copolymer. The authors carry out phase-diagram characterization for systems containing water, the copolymer, and the POM. After establishing the relevant equilibria and the effects of temperature, the authors characterize the micelles that are formed by NMR, SAXS and SANS. These powerful methods prove that in the monomer (premicellar) state of the block copolymer the POM interacts with the hydrophobic PPO units. Polymer micelles are forming depending on the concentration and temperature, and these micelles become elongated at higher temperatures. The POM now interacts more strongly with the PEO units that constitute the corona of the micelles. The conclusion is that both ion (super)chaotropicity (responsible for its interfacial activity) and the hydrophobic effect (responsible for the formation of polymeric micelles) determine the dominant structures in this complex system.

POMs are interesting since they are very large, yet sticky ions because of their small charge density. The present work provides one more look into their interesting interfacial properties. The work is well executed and the results novel and interesting enough; the SAXS and SANS modeling is sound and the combination of these two methods (one does not see it very much these days!) is quite illuminating. The topic of the investigation is interesting and timely. I therefore suggest that the paper may be accepted and published with very minor revisions.

We would like to thank the referee for these supportive statements on our research.

1. The decision to investigate this particular system is not very well explained. It sounds strange to say that, because we know that the POM interacts with PEO and PPO, we will examine how it interacts with a PEO-PPO copolymer.

We are thankful for this comment. In this study, we intentionally introduced that POM interacts with PEO and PPO in details. We believe strongly that the investigations and conclusions here, are only possible to be performed/drawn based on an incremental increase of knowledge. We would not have succeeded in interpreting all the experiments here, without the previous studies and therefore it is important to clearly state that the investigation of polymeric surfactants-POM interactions was performed based on the knowledge we have gained before. This is especially relevant, as polymeric surfactants in water (binary mixture) itself constitutes a highly complex system, as shown in section 3.1. In summary, it would not be possible to execute this study with two complex aspects: (i) superchaotropic effect and (ii) polymeric surfactants in water. Therefore, it was needed to build the current study around our current knowledge in order to tackle a complex system as POM/surfactant polymer mixtures.

However, the goal of our work was to gain a deeper knowledge on the interactions between a POM and organic molecules of different polarity (hydrophilicity/hydrophobicity) in water. We know that superchaotropic POMs interact with both PEO and PPO chains but we did not know to what extent. Therefore, the question of this work is: is there a specific interaction between PEO and PPO chains? It turns out that yes indeed POM (PW) interact more strongly with PPO as a result of an increased hydrophobic character compared to PEO. Increasing knowledge in this context is a first step towards designing formulations containing POM building blocks showing specific interactions, i.e. molecular recognition, with organic moieties. This deeper knowledge is required for future development of POM applications for instance in the medical field, for which pharmaceutical formulations containing POM and organic molecules (such as polymeric additives) need to be developed and specific interactions with biological molecules may be required.

 

We tried to make these points clear in the introduction and conclusion in order to give a clear justification on the choice of this polymeric system:

 

Discussion added in the introduction:

“Therefore, a controlled manipulation (e.g. controlling physicochemical solution properties such as the aggregation state or as rheology/viscosity) of polymeric surfactants via the chaotropic effect can be of high interest for a broad field of applications.

The goal of the present work is to gain a deeper knowledge on the interactions between a POM (HPW) and organic molecules of different polarity (hydrophilicity/hydrophobicity) in water. It is well known that superchaotropic POMs interact with both PEO and PPO chains but we do not know to what extent. Therefore, the underlying question of this work is: Is the interaction of HPW specific to PEO or to PPO chains? In other words: What is the effect of increasing hydrophobicity from PEO to PPO on the binding strength of HPW?”

 

Justification why we choose P84 and HPW:

“HPW was chosen as a model POM as it was shown previously to be the most superchaotropic POM among the well studied Keggin type. P84 was used because it allows (i) working on unimers and micelles in a temperature range, between room temperature and 60 °C, and it allows (ii) to measure a CP and its evolution upon POM addition which enables to evaluate simply the superchaotropic effect.”

 

Discussion added in the conclusion:

“We have shown here that HPW selectively adsorbs on the PPO moieties over the PEO chains, and thererfore we could conclude that HPW interact more strongly with PPO as a result of an increased hydrophobic character compared to PEO. A deeper knowledge on the interactions between a POM and organic molecules in water is a first step towards designing formulations containing POM building blocks showing specific interactions, i.e. towards molecular recognition. This deeper knowledge is required for future development of POM applications, for instance in the medical field[4] for which pharmaceutical formulations containing POM and organic molecules (such as polymeric additives[44]) could be developed and specific interactions with biological molecules may be required. We also can foresee applications of our findings for the control of polymeric surfactants as oil solubilizers or delivery systems, as the binding of POMs is likely to impact strongly the solubilizing efficiency of polymeric surfactant micelles. In conclusion, the balance of the chaotropic effect and the hydrophobic effect may play a decisive role in assembly of hierarchical functional systems.”

 

2. Why assume that the POM comes with 7 water molecules? Apart from previous experience, have the authors done any TGA on the commercial POM?

We are very grateful for this clarifying comment of the referee. Indeed, through this comment we found a typo in the manuscript. x_HPW = 17 and not as falsely written x_HPW = 7. This typo was corrected. The calculation of x_HPW is based on a TGA measurement, which is now stated in the manuscript. The TGA measurement is attached below with the according calculation.

 

84 mg HPW powder were prepared for TGA measurement. The vaporized water is 7.95 mg corresponding to 9.47 %. From the molar masses of HPW (2880 g/mol) and water (18 g/mol) a crystal water number of 16.74≈17 can be calculated.

 

3. The so-called “Langmuir fit” to the cloud-point concentration graph is an unfortunate procedure introduced by Cremer in a 2005 paper in JACS. Since then, this type of fitting has been used by several authors, but there is no theoretical justification for the application of Langmuir isotherms to cloud point curves and no clear way to explain/ understand the binding constants obtained from these fits.

We are thankful for this referee comment. Indeed, we fully agree with the reviewer’s comment. Fitting a temperature-dependent graph with an isothermal model promotes evident critical discussions. We are well aware of the limitation of using this approach. The Langmuir fit executed in this manuscript and other contributions (as mentioned by the referee) has two goals: (i) it gives a “rough” estimation of the association constants and (ii) it enables to classify POM, and more generally nano-ions according to a superchaotropicity scale.

We are currently working on this specific point by establishing the association constant by combining SAXS/SANS and comparing different association models to check the validity of the Langmuir model. There is, as expected, a difference in the association constant values that we get using these two approaches i.e. fitting the cloud point evolution upon POM addition with a Langmuir model and precisely determining the number of POM per micelle upon addition of POM with combined SAXS/SANS fitting of the micellar aggregates at a constant temperature). It turns out that (i) the order of magnitude in the association constant is correct between the two methods and (ii) the Langmuir adsorption model is valid to describe. We are finishing the manuscript on this question and hope it will close the discussion on this point.

 

We specified in the manuscript that fitting the CP evolution with a Langmuir model only gives a “rough” estimation of the binding constant.

 

4. Line 212 is incomprehensible.

The referee is right. This sentence refers to a very recent paper of Paul Cremer in Nature Chemistry, stating that chaotropic anions bind to polymers, but not to monomers (10.1038/s41557-021-00805-z). Due to the appearance of the terms monomers/unimers/polymers within one sentence, the sentence was hard to understand. We rephrased it and separated the sentence for better understanding:

“As a conclusion, HPW binds to P84 unimers which is due to its polymeric nature (81 repetition units) via the chaotropic effect. On the contrary, monomeric species (e.g. only one 1 “repetition” unit) are not expected to associate with a chaotropic anion[40] such as PW.”

 

5. The last sentence of the paper (lines 316-317) is not fully justified. It is not clear that the balance of hydrophobic and chaotropic effects will have a decisive effect “in the assembly of hierarchical systems” as the authors state. In fact, I have found the ending of the paper rather abrupt. One would expect to see a statement where to go from this point.

We thank the referee for this comment. We completely agree with his opinion. The last paragraph in the conclusion was rephrased in order to address this issue, as follows:

“We have shown here that HPW selectively adsorbs on the PPO moieties over the PEO chains, and thererfore we could conclude that HPW interact more strongly with PPO as a result of an increased hydrophobic character compared to PEO. A deeper knowledge on the interactions between a POM and organic molecules in water is a first step towards designing formulations containing POM building blocks showing specific interactions, i.e. towards molecular recognition. This deeper knowledge is required for future development of POM applications, for instance in the medical field[4] for which pharmaceutical formulations containing POM and organic molecules (such as polymeric additives[44]) could be developed and specific interactions with biological molecules may be required. We also can foresee applications of our findings for the control of polymeric surfactants as oil solubilizers or delivery systems, as the binding of POMs is likely to impact strongly the solubilizing efficiency of polymeric surfactant micelles. In conclusion, the balance of the chaotropic effect and the hydrophobic effect may play a decisive role in assembly of hierarchical functional systems.”

 

Author Response File: Author Response.pdf

Reviewer 2 Report

The team has conducted comprehensive research on characterizing and analyzing the structure and interactions of POM and block copolymer. For the benefit of audiences, please consider add discussions on:

1) the rationale of selecting P84/α-PW12O403 as model system;

2) the potential impacts of this research on science community and broader applications. 

Author Response

Referee 2:

The team has conducted comprehensive research on characterizing and analyzing the structure and interactions of POM and block copolymer. For the benefit of audiences, please consider add discussions on:

• the rationale of selecting P84/α-PW12O403 as model system;

We are grateful to the referee for this comment. The comment addresses the same aspect as for Referee 1, comment 1. Therefore, we would like to recall our answer on the comment to referee 1 here again:

In this study, we intentionally introduced that POM interacts with PEO and PPO in details. We strongly believe that the investigations and conclusions here, are only possible to be performed/drawn based on an incremental increase of knowledge. We would not have succeeded in interpreting all the experiments here, without the previous studies and therefore it is important to clearly state that the investigation of polymeric surfactants-POM interactions was performed based on the knowledge we have gained before. This is especially relevant, as polymeric surfactants in water (binary mixture) itself constitutes a highly complex system, as shown in section 3.1. In summary, it would not be possible to execute this study with two complex aspects: (i) superchaotropic effect and (ii) polymeric surfactants in water. Therefore, it was needed to build the current study around our current knowledge in order to tackle a complex system as POM/surfactant polymer mixtures.

However, the goal of our work was to gain a deeper knowledge on the interactions between a POM and organic molecules of different polarity (hydrophilicity/hydrophobicity) in water. We know that superchaotropic POMs interact with both PEO and PPO chains but we did not know to what extent. Therefore, the question of this work is: is there a specific interaction between PEO and PPO chains? It turns out that yes indeed POM (PW) interact more strongly with PPO as a result of an increased hydrophobic character compared to PEO. Increasing knowledge in this context is a first step towards designing formulations containing POM building blocks showing specific interactions, i.e. molecular recognition, with organic moieties. This deeper knowledge is required for future development of POM applications for instance in the medical field, for which pharmaceutical formulations containing POM and organic molecules (such as polymeric additives) need to be developed and specific interactions with biological molecules may be required.

 

We tried to make these points clear in the introduction and conclusion in order to give a clear justification on the choice of this polymeric system:

 

Discussion added in the introduction:

“Therefore, a controlled manipulation (e.g. controlling physicochemical solution properties such as the aggregation state or as rheology/viscosity) of polymeric surfactants via the chaotropic effect can be of high interest for a broad field of applications.

The goal of the present work is to gain a deeper knowledge on the interactions between a POM (HPW) and organic molecules of different polarity (hydrophilicity/hydrophobicity) in water. It is well known that superchaotropic POMs interact with both PEO and PPO chains but we do not know to what extent. Therefore, the underlying question of this work is: Is the interaction of HPW specific to PEO or to PPO chains? In other words: What is the effect of increasing hydrophobicity from PEO to PPO on the binding strength of HPW?”

 

Justification why we choose P84 and HPW:

“HPW was chosen as a model POM as it was shown previously to be the most superchaotropic POM among the well studied Keggin type. P84 was used because it allows (i) working on unimers and micelles in a temperature range, between room temperature and 60 °C, and it allows (ii) to measure a CP and its evolution upon POM addition which enables to evaluate simply the superchaotropic effect.”

 

Discussion added in the conclusion:

“We have shown here that HPW selectively adsorbs on the PPO moieties over the PEO chains, and thererfore we could conclude that HPW interact more strongly with PPO as a result of an increased hydrophobic character compared to PEO. A deeper knowledge on the interactions between a POM and organic molecules in water is a first step towards designing formulations containing POM building blocks showing specific interactions, i.e. towards molecular recognition. This deeper knowledge is required for future development of POM applications, for instance in the medical field[4] for which pharmaceutical formulations containing POM and organic molecules (such as polymeric additives[44]) could be developed and specific interactions with biological molecules may be required. We also can foresee applications of our findings for the control of polymeric surfactants as oil solubilizers or delivery systems, as the binding of POMs is likely to impact strongly the solubilizing efficiency of polymeric surfactant micelles. In conclusion, the balance of the chaotropic effect and the hydrophobic effect may play a decisive role in assembly of hierarchical functional systems.”

2) the potential impacts of this research on science community and broader applications. 

We thank the referee for this comment. We completely agree with his opinion. The last paragraph in the conclusion was rephrased in order to address this issue, as follows:

“This study shines light on the subtle balance of two effects: the chaotropic effect (binding of HPW to P84) and the hydrophobic effect (driving the micellization of P84 and the binding of HPW to P84).

We have shown here that HPW selectively adsorbs on the PPO moieties over the PEO chains, and thererfore we could conclude that HPW interact more strongly with PPO as a result of an increased hydrophobic character compared to PEO. A deeper knowledge on the interactions between a POM and organic molecules in water is a first step towards designing formulations containing POM building blocks showing specific interactions, i.e. towards molecular recognition. This deeper knowledge is required for future development of POM applications, for instance in the medical field[4] for which pharmaceutical formulations containing POM and organic molecules (such as polymeric additives[44]) could be developed and specific interactions with biological molecules may be required. We also can foresee applications of our findings for the control of polymeric surfactants as oil solubilizers or delivery systems, as the binding of POMs is likely to impact strongly the solubilizing efficiency of polymeric surfactant micelles. In conclusion, the balance of the chaotropic effect and the hydrophobic effect may play a decisive role in assembly of hierarchical functional systems.”

 

Author Response File: Author Response.pdf