Evaluation of a Resorcinarene-Based Sorbent as a Solid-Phase Extraction Material for the Enrichment of L-Carnitine from Aqueous Solutions

Round 1

Reviewer 1 Report

The manuscript by Maldonado and coworkers presents resorcinarenes with different lower rim chain lengths embedded into a copolymer backbone as new sorbents for the evaluation of pre-concentration of L-9 carnitine. The synthesis of resorcinarenes is well-developed, well-reported, and easy to accomplish. Unfuntionalized resorcinarenes also have limited applications due to their shallow cavity for guest binding. However, resorcinarenes embedded into polymeric networks could have new applications. This area has yet to be overly exploited and provides an avenue for new research into these old macrocycles.

The authors embedded these resorcinarenes through copolymerization between butylmethacrylate (BuMA) and ethylene dimethacrylate (EDMA). They characterize the unfunctionalized resorcinarenes via FTIR-ATR, 1H NMR, 13C NMR, and mass spectrometry, and the ones embedded into the polymers through FTIR-ATR and scanning electron micrography (SEM).

The authors studied host-guest binding between the unfunctionalized resorcinarenes towards L-carnitine in highly competing DMSO via 1H-NMR spectroscopy and electrospray ionization-mass spectrometry (ESI-MS). Proof of the embedded polymer-resorcinarene materials as sorbents for L-carnitine was done SEM and FT-IR. LC/MS analysis show the shorter lower rim resorcinarenes showing better results.

Major issues:

-          Why was the interaction between L-Carnitine and receptors 1-3, different from 4-5? The macrocycles all have the same cavity size. The only difference is the lower rim alkyl chain length.

Can the authors show the titration experiments with all the receptors?

-          Mass spectrometry should not be used to confirm stoichiometry, and definitely not in solution. Job plot and or ITC are better techniques.

Can the authors show the mass spec between l-carnitine and all the receptors? Figure 2 shows no interaction with receptors 4 and 5, again, why? The receptors all have the same cavity size and should bind the L-carnitine in the same manner.

-          The synthesis of the copolymer poly(BuMA-co-EDMA) is known and reported. The impregnation of the resorcinarenes onto the polymer backbone is unclear. The SEM and ATR-FTIR spectra  do not really show a clear difference between the pure copolymer and the copolymer embedded with the resorcinarenes. It is difficult to conclude the resorcinarenes are there. Without Supplemental information showing evidence of these claims, it is difficult to conclude from the provided data.

Some typos such as

-          Line 46: Not sure how generally acceptable SPE is compared to NMR or IR. Perhaps the full name at first use?

-          Line 179: 1H-RMN should be 1H-NMR

-          Line 259: The Legend is not clear.

This is a nicely written manuscript, but the main issues above should be addressed. 

Minor typos

Author Response

Please review file CLR-2387342 to see the responses to your comments 

Author Response File: Author Response.pdf

Reviewer 2 Report

The work presented in this paper provides a useful information in material science for synthesis of new sorbents and used for pre-concentration of L-carnitine. This manuscript presents a thorough and well conducted study on the synthesis and sorption properties. The introduction part covers the manuscript subject. I therefore recommend a minor revision

Below are listed a series of comments to be considered for improving the editing and content of this work before publication.
 Comments:

1.      The English language need minor revisions.

2.      The abstract should be rewritten and precise with more information.

3.      L 26-29, should be supported by more references

4.      Authors should support the introduction by conclusion part at the end.

5.      L170 -172 authors should support discussion by brief details of the synthesis.

Need minor revisions

Author Response

Please review file CLR-2387342 to see the responses to your comments

Author Response File: Author Response.pdf

Reviewer 3 Report

The present manuscript by Mauricio Maldonado and co-workers reported on resorcinarene-based sorbents as extraction material for the enrichment of L-carnitine from aqueous solutions. The manuscript is written very sloppily. There are a lot of misprints in the text. Moreover, the supplementary material would be very helpful in evaluating the manuscript. As for the current status, I suggest that the present manuscript might be considered for publication after serious revision.

Major points:

Why did the authors use only 1:0.1 and 1:2 amounts of L-carnitine?

How could the authors explain that macrocycles 4 and 5 did not dissolve in DMSO but had a good solubility in chloroform? This is very interesting and unusual fact.

In the Materials&Methods and at the beginning of Results&Discuccion the authors gave full characterization of previously synthesized macrocycles 1-5. How could the authors explain the need for a complete characterization of previously synthesized macrocycles?

The authors have shown a figure of an interaction only between macrocycle 2 and L-carnitine. Other figures with an interaction between L-carnitine and macrocycles 1 and 3-5 should also be given.

The authors wrote in Materials&Methods that an interaction between macrocycles 4 and 5 and L-carnitine did not investigate due to low solubility of these calix[4]resorcinarenes. But in Results&Discuccion the authors wrote that “the interaction of L-carnitine with 4 and 5 was considerably much lower”. What does it mean?

As far as I understand, figure 3 shows SEM images of macrocycles 1 and 3. At the same time, the authors discussed in the manuscript compounds 1 and 2, what about the porosity of compound 3? Please, discuss it.

The authors claimed “resorcinarerene 1 presented the best interaction with carnitine in aqueous solution”. How did the authors determine that it interacts in the best way?

“As was evident from the results, the extraction recovery reached a maximum at 60 min…” – about which results the authors discussed?

Minor points:

Via and d6 in DMSO should be italics. Please, check and correct it throughout the manuscript.

In the “Synthesis of Calix[4]resorcinarenes” the authors wrote the following sentence “The procedure for obtaining…” without any references. Please, add necessary references.

179 line – “RMN” should be “NMR”.

The authors should improve the sharpness and quality of the SEM figures. In the current figures there no pores visible.

The manuscript is written very sloppily. There are a lot of misprints in the text. 

Author Response

Please review file CLR-2387342 to see the responses to your comments

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

The authors have addressed all the reviewers' concerns. The manuscript can now proceed to the next step of the publishing circle. I do encourage the authors to provide high quality images especially figure 2 and some of the mass spec figures in the SI. 

N/A

Author Response

please check attached file

Author Response File: Author Response.pdf

Reviewer 3 Report

The authors improved the manuscript and clarified all doubts. But there is still no the supplementary material which would be very helpful in evaluating the manuscript. 

 

Author Response

Please check attached file

Author Response File: Author Response.pdf