Application of Κ-Carrageenan for One-Pot Synthesis of Hybrids of Natural Curcumin with Iron and Copper: Stability Analysis and Application in Papilloscopy
, Amanda Fonseca Leitzke 1,3, Juliana Porciúncula da Silva 1, Daisa Hakbart Bonemann 1,2, Gabrielly Quartieri Sejanes 1, Bruno Nunes da Rosa 1,2, TaÃs Poletti 1,2, Guilherme Kurz Maron 2, Bruno Vasconcellos Lopes 2, Matheus de Paula Goularte 2,4, Darci Alberto Gatto 4, André Luiz Missio 2, Neftali Lenin Villarreal Carreno 2 and Claudio Martin Pereira de Pereira 1,2,3,*
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsReview of the paper
Application of Κ-Carrageenan for One-Pot Synthesis of Hybrids of Curcumin Natural with Iron and Copper: Stability Analysis and Application in Papilloscopy
The paper is interesting and fairly written in general.
There are however a few points to be corrected:
1) Section “Synthesis of the hybrid materials”.
The mass of the reagents (in grams) is presented with four significant digits, whereas the amount of substance (in mmol) is just shown with one-two digits.
Please, correct this.
2) Scheme 1 does not give any information on the chemical reactions. Please provide a list of them. If there is a long list, the most principal could be provided.
3) Please check the correctness of eq. (1). Maybe the denominator should be 3? Besides, if all the variables in the right side are squared, maybe the left side should also be squared?
4) What are the prospects of industrial production by means of the studied method? Is it possible to use some known devices for production or some special devices are needed?
Author Response
Comments 1) [Section “Synthesis of the hybrid materials”.
The mass of the reagents (in grams) is presented with four significant digits, whereas the amount of substance (in mmol) is just shown with one-two digits.
Please, correct this.]
Response 1) [The mass in grams and mmol was standardized and corrected.]
Comments 2) [Scheme 1 does not give any information on the chemical reactions. Please provide a list of them. If there is a long list, the most principal could be provided.]
Response 2) [The Scheme 1 has been adapted to show the stages of the chemical reactions, which have been described in the legend.]
Comments 3) [Please check the correctness of eq. (1). Maybe the denominator should be 3? Besides, if all the variables in the right side are squared, maybe the left side should also be squared?]
Response 3) [In order to be more understandable, the Equation has been adjusted.]
Comments 4) [What are the prospects of industrial production by means of the studied method? Is it possible to use some known devices for production or some special devices are needed?]
Response 4) [The synthesis of these materials on a large scale is feasible because the method utilized only requires a recipient and a stirring plate, which simplifies the process and makes it possible to scale up production without the need for sophisticated equipment. The scalability of production with these conventional devices makes the method more accessible to the industrial sector, promoting an efficient and low-cost production model.]
Reviewer 2 Report
Comments and Suggestions for AuthorsI found the manuscript interesting. I have few comments before accepting the manuscript.
1-I found in literature comparable methodologies and technical approaches (to some extent). Please clarify motivations and novelties more properly.
2-What are the added-values of bioactive compounds toward developing novel food and pharmaceutical applications?
3-The spectroscopy analysis required more elaboration. Mainly Figure 2.
4-Stability analysis is not really evident. I think something is missed here.
Comments on the Quality of English LanguageGood
Author Response
Comments 1 -I found in literature comparable methodologies and technical approaches (to some extent). Please clarify motivations and novelties more properly.
Response 1 - Curcumin instability is a limiting factor for its application in various fields, given its susceptibility to degradation under adverse environmental conditions. This context makes the synthesis of hybrid materials aimed at stabilizing curcumin a promising approach, thus enhancing its application potential. Although similar methodologies are described in the literature, such as the work of Li et al. (2021) using palygorskite for stabilization, our approach innovates by employing Kappa-carrageenan as a stabilizing agent. This polysaccharide, extracted from macroalgae, offers significant properties for hybrid materials: it is biodegradable, biocompatible, edible, and low-cost, in addition to being biologically safe. Kappa-carrageenan has a negatively charged surface, which enables efficient electrostatic interactions with metal ions at the beta-diketone fraction of curcumin, conferring greater stability to the hybrid compound. Therefore, this study proposes a sustainable and economically viable alternative, with a positive impact on the applications of stabilized curcumin.
In order to determine curcumin, we adapted the method described by Anjani et al. (2022) to specifically meet the needs of this work. The original study used gradient elution, but we opted for the isocratic mode, as we focused solely on identifying curcumin. Thus, we adjusted the mobile phase to the ratio in which curcumin was identified in Anjani's study. Since the sample used in this study was not completely pure, we applied temperature control to improve the separation of curcuminoids. We maintained the detection wavelength, mobile phase type, and C18 column as in the original method, ensuring compatibility and accuracy. These adaptations provided a robust and efficient identification of curcumin, offering a technical alternative to the reference method and broadening its applicability.
To determine the stability in solution of curcumin and the hybrid materials, we adapted the method from Kumar et al. (2021). We retained key elements from the original methodology, such as the column type, detection wavelength, injection volume, flow rate, and type of mobile phase. However, we adjusted the solvent percentages in the mobile phase to optimize peak resolution and improve detection accuracy. Unlike Kumar’s study, we examined the stability of the compounds in acetonitrile rather than a buffer solution, as our focus does not involve biological applications for the synthesized compounds. This choice aims to align the experimental parameters with the intended real-use conditions, providing an innovative and practical adaptation of the reference method to meet the needs of this work.
Comments 2-What are the added-values of bioactive compounds toward developing novel food and pharmaceutical applications?
Response 2 - Bioactive compounds, such as curcumin, possess high-value functional properties that enable new possibilities for various pharmaceutical and food applications. In addition to being used as fingerprint developers, these compounds show significant potential in pharmaceutical formulations due to their well-known anti-inflammatory, antioxidant, antimicrobial, and anticancer properties, expanding their use in treatments and prevention of chronic diseases, infections, and inflammatory conditions. In the food industry, bioactives can serve as natural preservatives, promoting stability and offering functional and nutraceutical benefits that enhance consumer health. Stabilizing these compounds in hybrid matrices further enhances their bioavailability and efficacy, making them a safe and effective option for new pharmaceutical products and functional foods, while also demonstrating their versatility for future innovations across various industries.
Comments 3 - The spectroscopy analysis required more elaboration. Mainly Figure 2.
Response 3 - The resolution of Figure 2 has been adjusted to improve clarity and facilitate data interpretation. We believe the comment may refer to the visual quality of the image, but if the feedback is related to the spectral analysis itself, please let us know so we can enhance the description and discuss the data in greater depth.
Comments 4 - Stability analysis is not really evident. I think something is missed here.
Response 4 - The stability analysis has been detailed in the Discussion section of the article to provide greater clarity. We have incorporated additional information to make the stability study more evident and well-founded. The revised text can be found on lines 398 - 409.
"The instability of curcumin has been investigated in previous studies, where curcumin was dissolved in ethanol [42] or in phosphate-buffered saline (PBS) [16]. Under these conditions, degradation products such as vanillin, vanillic acid, and ferulic acid were identified [51, 18]. In particular, curcumin degradation was detected after 24 hours of incubation, observed by a reduction in the corresponding peak height, as previously reported [16]. Figures 4A and 4B clearly illustrate the decrease in curcumin peak intensity after 24 hours, as well as the appearance of new peaks corresponding to degradation products with retention times longer than that of curcumin, consistent with the findings of Kumar et al. (2021) [16], as shown in Figure 4B. In contrast, no degradation products were observed in the hybrid materials. Figures 4C and 4D show the same intensity and peak behavior at all analyzed times, corroborating the results of Kumar et al. (2021) for curcumin-based metal complexes [16]."
Reviewer 3 Report
Comments and Suggestions for AuthorsThe submitted manuscript (ID: colorants-3270590) might be a helpful proposal towards "One-Pot Synthesis of Hybrids of Curcumin Natural with Iron (and Copper)". However, whenever might be resubmitted should contain some critical (and basic) additions on (magnetic properties of) their 1)Fe-composite materials and their 2)fingerprints' samples (offering greater clarity). Weak magnetic cohesive (intergraine) forces might support/result for the good statements: 1)'When comparing both composites, the Fe one stood out by providing greater sharpness, resulting in clearer definition of fingerprint minutiae (Line_479)', and the statement, 2)"it was observed that the Fe composite offered greater clarity compared to the Cu composite, which is directly related to the strong adhesion of the Fe composite to the fingerprint compounds (Line_507)". Also, there are some (2)major and (6)minor notes/corrections.
A) Some (2) major notes/corrections:
1. Line_031: Modify/delete a phrase. Replace "due to" by 'maybe due to', or even better, delete the misleading phrase, ', due to minimal interaction of Fe with the glass surface.', in: "composite compared to the Cu composite, due to minimal interaction of Fe with the glass surface.".
2. Line_231: About (Cu and Fe) concentration measurements. How/what measurements revealed the concentration of Cu and Fe (in the hybrid materials), in: "the concentration of Cu and Fe in the hybrid materials, values of 13.31 and 13.51 mg g-1,".
Also,
B) there are some (6) minor notes/corrections:
1. Line_095: A typing error(?). Replace 'LFO', by "LFP"(?), in: "these hybrid composites were tested as potential LFO developers, offering a novel, low-".
2. Line_146: A typing/term error(?). Replace '5 ?M', by "5 ?m", in: "particle size of 5 ?M, a pore size of 90 , and 15 cm x 4.6 mm in size. For the determination".
3. Line_162: About "silver mica powder" infos. Say more about "silver mica powder", in: "Fe and Cu hybrid composites [25]. Briefly, copper or iron precursor, silver mica powder,".
4. Line_243: About (XRD operational) mode. The presented (in Fig.2B) XRD are (all) under similar (and the same, reflection or transmition mode) conditions (?) , in: "ther investigated through XRD and the results are presented in Figure 2B. The XRD pat- ".
5. Line_306: More infos for numbers (inside red circles,in Figure 5). Say more the white numbers inside red background circles in Figure 5 (and in Figure 6), in: "Figure 5. Natural and sebaceous fingerprints developed with the Cu hybrid composite".
6. Line_337: About the SEM (in Fig.10). Is there any (add on) conductive (Carbon,...?) layer on the latent fingerprints(?), in: "Figure 10. SEM analysis of natural and sebaceous latent fingerprints developed with Cu and Fe composites on a glass surface.".
The language of the submitted manuscript (ID: colorants-3270590) is not bad.
Author Response
Comments 1) The submitted manuscript (ID: colorants-3270590) might be a helpful proposal towards "One-Pot Synthesis of Hybrids of Curcumin Natural with Iron (and Copper)". However, whenever might be resubmitted should contain some critical (and basic) additions on (magnetic properties of) their 1)Fe-composite materials and their 2)fingerprints' samples (offering greater clarity). Weak magnetic cohesive (intergraine) forces might support/result for the good statements: 1)'When comparing both composites, the Fe one stood out by providing greater sharpness, resulting in clearer definition of fingerprint minutiae (Line_479)', and the statement, 2)"it was observed that the Fe composite offered greater clarity compared to the Cu composite, which is directly related to the strong adhesion of the Fe composite to the fingerprint compounds (Line_507)". Also, there are some (2)major and (6)minor notes/corrections.
Response 1: The relationship between the improved performance of the Fe hybrid composite and the weak magnetic cohesion forces has been added and expanded in the discussion section, in order to clarify the factors that contributed to the better development of fingerprints with the Fe composite. This update highlights how the weaker intergraine magnetic interactions facilitate the adhesion of the composite to the details of the papillary ridges, resulting in greater sharpness and contrast in the fingerprints. Detailed information can be found in lines 486 - 493 of the revised manuscript.
A) Some (2) major notes/corrections:
Comments 2) 1. Line_031: Modify/delete a phrase. Replace "due to" by 'maybe due to', or even better, delete the misleading phrase, ', due to minimal interaction of Fe with the glass surface.', in: "composite compared to the Cu composite, due to minimal interaction of Fe with the glass surface.".
Response 2) As requested, the phrase was deleted.
Comments 3) 2. Line_231: About (Cu and Fe) concentration measurements. How/what measurements revealed the concentration of Cu and Fe (in the hybrid materials), in: "the concentration of Cu and Fe in the hybrid materials, values of 13.31 and 13.51 mg g-1,".
Response 3) The determination of metal concentrations in Cu and Fe hybrid materials was performed using flame atomic absorption spectrometry, following acid decomposition in a digestion block. This technique quantifies the concentration of metallic elements in the resulting solution from the decomposition process. The equipment used employs an energy source consisting of hollow cathode lamps, specific to the metal being analyzed. The sample is converted into an aerosol of small droplets, which is aspirated into the atomizer, consisting of a flame with a temperature range of 2000 to 3000 K. Electromagnetic radiation emitted by the source strikes the atomizer, and the characteristic spectral lines of the metal are selected by a monochromator, which directs the corresponding line to the detector. For metal quantification, a linear calibration curve is generated by the equipment using solutions of known concentration. The samples are then aspirated, and the metal concentration is measured in mg/L. Knowing the mass of the hybrid material sample subjected to decomposition, the concentration is expressed in terms of mass/mass (m/m), i.e., in mg/g of sample.
Also,
Comments 4) B) there are some (6) minor notes/corrections:
1. Line_095: A typing error(?). Replace 'LFO', by "LFP"(?), in: "these hybrid composites were tested as potential LFO developers, offering a novel, low-".
Response 4) The typing error was correted.
Comments 5) 2. Line_146: A typing/term error(?). Replace '5 ?M', by "5 ?m", in: "particle size of 5 ?M, a pore size of 90 , and 15 cm x 4.6 mm in size. For the determination".
Response 5) The typing error was corrected.
Comments 6) 3. Line_162: About "silver mica powder" infos. Say more about "silver mica powder", in: "Fe and Cu hybrid composites [25]. Briefly, copper or iron precursor, silver mica powder,".
Response 6) Silver mica powder is a pearlescent pigment known for its shiny, lustrous appearance. Its color variation is due to coatings with different metal oxides. The basic structure is TiO2, and the specific coloration depends on the metal oxide present; in the case of this work, we used silver, resulting in silver mica powder with the chemical formula TiO2/Ag2O. This material is widely used in the cosmetics industry due to its aesthetic properties. The chemical formula of the silver mica powder used has been included in the text on line 166 for clarity.
Comments 7) 4. Line_243: About (XRD operational) mode. The presented (in Fig.2B) XRD are (all) under similar (and the same, reflection or transmition mode) conditions (?) , in: "ther investigated through XRD and the results are presented in Figure 2B. The XRD pat- ".
Response 7) All the samples were analyzed under the same operating conditions, using the reflection mode with a 2θ range from 10° to 60°. To improve the understandment of the results, the text has been revised and adjusted. Figure 2B now presents this data more clearly, reflecting the consistency in the analysis conditions.
Comments 8) 5. Line_306: More infos for numbers (inside red circles,in Figure 5). Say more the white numbers inside red background circles in Figure 5 (and in Figure 6), in: "Figure 5. Natural and sebaceous fingerprints developed with the Cu hybrid composite".
Response 8) The discussion regarding the scores assigned to the fingerprints has been expanded to include both composites and can be found on lines 428 - 444. The white numbers inside the red-background circles, present in Figures 5 and 6, represents the scores of the development of the fingerprints, indicating the level of detail and clarity achieved for each fingerprint developed with the hybrid composites of Cu and Fe.
Comments 9) 6. Line_337: About the SEM (in Fig.10). Is there any (add on) conductive (Carbon,...?) layer on the latent fingerprints(?), in: "Figure 10. SEM analysis of natural and sebaceous latent fingerprints developed with Cu and Fe composites on a glass surface.".
Response 9: Yes, it is necessary the application of a conductive layer. For this, we use a carbon tape between the stub and the glass surface where the fingerprint is deposited.
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsThe authors have replied all the questions, the paper is ready now for publication.
Reviewer 2 Report
Comments and Suggestions for AuthorsManuscript has replied to my comments in a satisfactory way. I recommend the publication of the present work.
Comments on the Quality of English LanguageGood
Reviewer 3 Report
Comments and Suggestions for AuthorsThe resubmitted manuscript (ID: colorants-3270590-v2) is better and it is recommended to accept in the present form.
