Synthesis and Characterization of Poly(DL-lactide) Containing Fluorene Structures

Round 1

Reviewer 1 Report

The article is well-written but lacks error measurements. Therefore, it needs major revision. The correction needed:

1. Please add errors of measurement.

2.  Please add regression of error.

3.  Use superscripts in units and avoid sticking to values and units like in section 2.3

Author Response

To Referee #1:

1. Please add errors of measurement.

Thank you for your suggestion.In section 2.4.2, Table 1, we have included the text "GPC of Calibration curve, R=0.9986", and in Figure 8, we have added error bars.

2. Please add regression of error.

Thank you for your suggestion.In section 2.4.2, Table 1, we have included the text "GPC of Calibration curve, R=0.9986", and in Figure 8, we have added error bars.

3. Use superscripts in units and avoid sticking to values and units like in section 2.3

Thank you for your suggestion. These corrections have made in the revised manuscript.

Reviewer 2 Report

In the submitted manuscript by Lin and co-workers, poly(DL-lactide) (PDLLA) samples are prepared from ring-opening polymerization of DL-lactide using 9,9-bis[4-(2-hydroxy-3-acryloyloxypropoxy)phenyl]fluorene (BPF) as the initiator with varying ratios of DL-lactide monomer and BPF initiator. The polymerization is initiated by the two hydroxyl groups on BPF to produce poly(lactide), while the tow acrylate groups on BPF enables photocrosslinking leading to network structures. The structure of these polymer samples before and after photocrosslinknig are characterized by nuclear magnetic resonance (NMR) and gel permeation chromatography. In addition, the gel content, refractive index, thermal properties (differential scanning thermometry (DSC) and thermogravimetric analysis (TGA)), and cytotoxicity of these polymer products are also tested. Overall, the authors have demonstrated a strategy to prepare crosslinkable poly(DL-lactide) by using BPF as the initiator. However, the manuscript contains several typos, and the formatting should be corrected in a consistent manner. This work could be suitable for Polymers, and acceptance with major revisions is recommended after addressing the points listed below.

·       Please make sure the capitalization is correct across the manuscript, including titles and headings.

·       Please check that spaces are correctly used between two sentences, two words, after punctuation, or between the numerical value and unit symbol.

·       Please correct figure caption numbers in both main text and figures.

·       All the figures have low resolution, and some labels are really hard to read.

·       Tm and Tg should be T_m and T_g

·       Mn and Mw should be M_n and M_w

·       For the unit of wavelength in FT-IR measurement, “cm-1” could be “cm^-1”

·       Section 2.1 Materials – what does the underscore before the percentage purity mean? (for instance, DL-Lactide (_99.5%))

·       Section 2.2. Synthesis of DL-BPF, last sentences – “while” should be deleted.

·       Section 2.3. Photocrosslinking conditions – “cm2” should be “cm²”.

·       Section 2.4.3. Differential scanning calorimetry (DSC) – this title should not be italic.

·       Section 2.4.3. Differential scanning calorimetry (DSC) – the last two sentences describing the way to obtain T_g have similar meanings. I think “The midpoint of the change in slope of the heat capacity plot during the heating scan was taken as the glass transition temperature.” could be deleted.

·       Section 2.4.8. Hydrolytic degradation tests – a period is missing in the end.

·       Section 3.1 –  I don’t think describing all the peak assignments on ¹H and ¹³C NMR is necessary, since they are all labeled in the figures. Only the important peaks need to be emphasized.

·       I think the produced polymers are poly(lactide) homopolymers not copolymers, because BPF is an initiator not a monomer.

The manuscript contains several typos, and the formatting should be corrected in a consistent manner.

Author Response

To Referee #2:

1. Please make sure the capitalization is correct across the manuscript, including titles and headings.

Thank you for your suggestion. These corrections have made in the revised manuscript.

2. Please check that spaces are correctly used between two sentences, two words, after punctuation, or between the numerical value and unit symbol.

Thank you for your suggestion. These corrections have made in the revised manuscript.

3. Please correct figure caption numbers in both main text and figures.

Thank you for your suggestion. These corrections have made in the revised manuscript.

4. All the figures have low resolution, and some labels are really hard to read.

Thank you for your suggestion. I apologize for the previous oversight.These corrections have made in the revised manuscript.

5. Tm and Tg should be T_mand T_g

Thank you for your suggestion. These corrections have made in the revised manuscript.

6. Mn and Mw should be M_nand M_w

Thank you for your suggestion. These corrections have made in the revised manuscript.

7. For the unit of wavelength in FT-IR measurement, “cm-1” could be “cm-1”

Thank you for your suggestion. These corrections have made in the revised manuscript.

8. Section 2.1 Materials – what does the underscore before the percentage purity mean? (for instance, DL-Lactide (_99.5%))

Thank you for your suggestion. These corrections have made in the revised manuscript.

9. Section 2.2. Synthesis of DL-BPF, last sentences – “while” should be deleted.

Thank you for your suggestion. These corrections have made in the revised manuscript.

10. Section 2.3. Photocrosslinking conditions – “cm2” should be “cm2”.

Thank you for your suggestion. These corrections have made in the revised manuscript.

11. Section 2.4.3. Differential scanning calorimetry (DSC) – this title should not be italic.

Thank you for your suggestion. These corrections have made in the revised manuscript.

12. Section 2.4.3. Differential scanning calorimetry (DSC) – the last two sentences describing the way to obtain Tg have similar meanings. I think “The midpoint of the change in slope of the heat capacity plot during the heating scan was taken as the glass transition temperature.” could be deleted.

Thank you for your suggestion. These corrections have made in the revised manuscript.

13. Section 2.4.8. Hydrolytic degradation tests – a period is missing in the end.

Thank you for your suggestion.I apologize for the previous oversight. We have now corrected the title.

14. Section 3.1 –  I don’t think describing all the peak assignments on¹H and ¹³C NMR is necessary, since they are all labeled in the figures. Only the important peaks need to be emphasized.

Thank you for your suggestion. These corrections have made in the revised manuscript.

15. I think the produced polymers are poly(lactide) homopolymers not copolymers, because BPF is an initiator not a monomer.

Thank you very much for your kind suggestions. We utilized the hydroxyl groups (-OH) on BPF as initiators for the ring-opening polymerization reaction.

We have made revisions to the abstract and content of the manuscript.

9,9-bis[4-(2-hydroxy-3-acryloyloxypropoxy)phenyl]fluorene (BPF) hydroxyl groups (-OH) were used as initiators in the ring-opening polymerization reaction with DL-lactide monomers at different molar ratios to synthesize a poly(DL-lactide) polymer containing bisphenol fluorene structure and acrylate functional groups (DL-BPF)

In this study, our goal was to utilize the hydroxyl groups (-OH) of BPF as initiators for ring-opening polymerization (ROP) with DL-lactide monomers.

In this study, we employed the -OH groups on the molecular chain of 9,9-bis[4-(2-hydroxy-3-acryloyloxypropoxy)phenyl]fluorene (BPF) as initiators and adjusted the molar ratios of DL-lactide monomers in the ring-opening polymerization reaction.

Reviewer 3 Report

The focus of the manuscript entitled "Synthesis and Characterization of Poly(DL-lactide) containing Fluorene structures" (id. 2395647) is on the synthesis and properties of pristine and crosslinked polymers containing polylactic moieties linked to a fluorene derivative. The target compounds are of interest because of their plausible biodegradability and remarkable optical and fluorescent characteristics, which can be utilized in industry.

In my opinion, the manuscript is worthy publishing after the authors answer the questions and address the comments given below to improve the manuscript quality and comprehensibility.

The abbreviations (PDLLA, p.2; ATR, p.4; MTT, p.4) should be explained at their first mention. The symbolic notations of melting, glass temperatures etc. should be presented throughout using subscripts rather than in a line.

The sentences containing "Take monomer" (p.2), "sieve the fine powder" (p.4) should be corrected to passive voice.

The spaces should be placed where appropriate throughout the manuscript.

Why did the authors add 4-methoxyphenol as inhibitor at the beginning of the reaction?

Scheme 1 and all Figures are of very poor quality. Please improve.

What is the purpose of presenting four images in Figure 1? All the four samples look identical. Whichever they are, the picture quality does not allow distinguishing any differences.

It is not clear from Section 2.4 subsections if the pristine or crosslinked polymer is under examination.

2.4.2: What was the solvent for the polymer application onto the column? What was the column and the stationary phase? What was the temperature? What were the polystyrene standards and where were they purchased?

2.4.6: How did the authors find out that it is the gel fraction that is insoluble in acetone? According to 2.3, acetone was removed after photocrosslinking. What material then makes up the gel?

Section 2.4.8 is entitled "Hydrolytic degradation tests." However, it contains the description of the cytotoxicity measurements.

In Results, there is virtually no characterization or discussion of the FTIR spectra from Figure 4.

Minor editing of English is needed. Some of the required corrections are indicated in the report.

Author Response

 To Referee #3:

1. The abbreviations (PDLLA, p.2; ATR, p.4; MTT, p.4) should be explained at their first mention. The symbolic notations of melting, glass temperatures etc. should be presented throughout using subscripts rather than in a line.

Thank you for your suggestion. These corrections have made in the revised manuscript.

2. The sentences containing "Take monomer" (p.2), "sieve the fine powder" (p.4) should be corrected to passive voice.

Thank you for your suggestion. These corrections have made in the revised manuscript.

The DL-lactide and the 9,9-bis[4-(2-hydroxy-3-acryloyloxypropoxy)phenyl]fluorene(BPF) in molar ratios of 5:1, 10:1,15:1, 20:1 respectively were placed in a 250 mL flask with three necks and dried under vacuum for 1 h.

The photocrosslinked lumps of DL-BPF were crushed and then sieved with a standard sieve of #35.

3. The spaces should be placed where appropriate throughout the manuscript.

Thank you for your suggestion. These corrections have made in the revised manuscript.

4. Why did the authors add 4-methoxyphenol as inhibitor at the beginning of the reaction?

Thank you for your suggestion.

4-methoxyphenol was added to prevent the acrylate double bonds on BPF from undergoing free radical polymerization during the ring-opening polymerization reaction. In the purification process of the polymer, 4-methoxyphenol is subsequently washed away and removed.

5. Scheme 1 and all Figures are of very poor quality. Please improve.

Thank you for your suggestion. I apologize for the previous oversight.These corrections have made in the revised manuscript.

6. What is the purpose of presenting four images in Figure 1? All the four samples look identical. Whichever they are, the picture quality does not allow distinguishing any differences.

Thank you for your suggestion.In Figure 1, we aim to depict the states of DL-BPF polymers with different molar ratios after photocrosslinking.

7. It is not clear from Section 2.4 subsections if the pristine or crosslinked polymer is under examination.

Thank you for your suggestion. We have made revisions to the content of Section 2.4 of the manuscript.

8. 4.2: What was the solvent for the polymer application onto the column? What was the column and the stationary phase? What was the temperature? What were the polystyrene standards and where were they purchased?

Thank you for your suggestion. We revised section 2.4.2 of the manuscript.

The measurement conditions were as follows: the mobile phase was THF, the temperature was set at 35℃, the flow rate of the mobile phase was 10 mL/min, and polystyrene was used as the calibration standard.The polystyrene standard was obtained from POLYMER STANDARDS SERVICE (PSS). The GPC column setup consisted of three columns in series: Jordi Gel DVB Mixed Bed, Waters Styragel®HR4E THF, and Waters Styragel®HR3 THF. The molecular weight was calculated based on the calibration curve obtained using the polystyrene standard, with an R-value of 0.9986. The tested sample is uncrosslinked DL-BPF polymer.

9. 4.6: How did the authors find out that it is the gel fraction that is insoluble in acetone? According to 2.3, acetone was removed after photocrosslinking. What material then makes up the gel?

Thank you for your suggestion.

After photocrosslinking, the DL-BPF polymer was immersed in acetone at 50℃ for 12 hours. It was observed that the photocrosslinked DL-BPF did not dissolve in acetone, while the non-crosslinked DL-BPF completely dissolved. Therefore, after removing the acetone, the product obtained was the DL-BPF photocrosslinked polymer.

10. Section 2.4.8 is entitled "Hydrolytic degradation tests." However, it contains the description of the cytotoxicity measurements.

Thank you for your suggestion.I apologize for the previous oversight. We have now corrected the title.

11. In Results, there is virtually no characterization or discussion of the FTIR spectra from Figure 4.

Thank you for your suggestion.

In Figure 5, the FTIR spectrum specifically focuses on the characteristic peak wavelength at 1635 cm^-1, corresponding to the double bonds (C=C) present in the DL-BPF polymer before and after photocrosslinking. However, this suggestion can serve as a guideline for future related research.

Round 2

Reviewer 1 Report

Thank You very much for your cooperation.

Published.

Author Response

To Referee #1:

Thank you for the reviewer's suggestions and guidance. I appreciate it.

Reviewer 2 Report

The authors have addressed most of my concerns, as the typos have been corrected and the formatting is consistent. However, for some reasons the figures still have low resolution. For instance, I can hardly read labels in the NMR spectra in figure 2 and 3. I am not sure if this issue occurred during the uploading of the document. I think the revised manuscript is suitable for publication after addressing the issue of low-resolution figures.

I think the writing is mostly good after correction of the formatting issues and typos.

Author Response

To Referee #2:

Thank you for your suggestion.

After conducting our tests, it seems that there may have been a problem during the upload or file conversion process. We will provide the reviewer with the original image files for reference. Furthermore, we will also send all the image files to the editors for their review. Thank you.

Author Response File: Author Response.docx