
==== Front
Sci Rep
Sci Rep
Scientific Reports
2045-2322
Nature Publishing Group UK London

71655
10.1038/s41598-024-71655-1
Article
Investigating the electronic properties of edge glycine/biopolymer/graphene quantum dots
El-Sayed Nayera M. 1
Elhaes Hanan 2
Ibrahim Asmaa 2
Ibrahim Medhat A. ma.khalek@nrc.sci.eg

34
1 https://ror.org/01k8vtd75 grid.10251.37 0000 0001 0342 6662 Physics Department, Faculty of Science, Mansoura University, Mansoura, 35516 Egypt
2 https://ror.org/00cb9w016 grid.7269.a 0000 0004 0621 1570 Physics Department, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, 11757 Egypt
3 https://ror.org/02n85j827 grid.419725.c 0000 0001 2151 8157 Spectroscopy Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza, 12622 Egypt
4 https://ror.org/02n85j827 grid.419725.c 0000 0001 2151 8157 Molecular Modeling and Spectroscopy Laboratory, Centre of Excellence for Advanced Science, National Research Centre, 33 El-Bohouth St., Dokki, Giza, 12622 Egypt
20 9 2024
20 9 2024
2024
14 219737 3 2024
29 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
This study systematically investigated four types of graphene quantum dots (GQDs) AHEX, ZTRI, ZHEX, and ATRI, and their interactions with glycine to form GQD-glycine complexes. Utilizing density functional theory (DFT) and the PM6 semiempirical method, the study analyzed electronic properties and structure-activity relationships. Global reactivity indices were calculated using Koopmans’ theorem, and quantitative structure-activity relationship (QSAR) parameters were assessed via SCIGRESS 0.3. The study further explored interactions using density of states (DOS) and quantum theory of atoms in molecules (QTAIM) analyses. Key findings revealed that glycine interaction significantly increased the total dipole moment (TDM) and decreased the HOMO/LUMO energy gap (ΔE) for the GQD-glycine complexes. Notably, ZTRI/glycine showed a TDM of 4.535 Debye and a reduced ΔE of 0.323 eV, indicating enhanced reactivity. Further interactions with cellulose, chitosan, and sodium alginate identified the ZTRI/glycine/sodium alginate composite as the most reactive, with a TDM of 8.020 Debye and the lowest ΔE of 0.200 eV. This composite also exhibited the highest electrophilicity index (56.421) and lowest chemical hardness (0.145 eV), underscoring its superior reactivity and stability. DOS analysis revealed that biomolecules contributed the most to molecular orbitals, with carbon atoms contributing the least. QTAIM analysis confirmed the greater stability of the ZTRI/glycine/sodium alginate complex compared to other studied composites. These results highlight the enhanced reactivity and stability of GQDs when interacting with glycine and sodium alginate.

Keywords

GQDs
Glycine
TDM
HOMO/LUMO and MESP
Subject terms

Materials science
Physics
Science; Technology & Innovation Funding Authority (STDF)47336 National Research Centre EgyptOpen access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).

issue-copyright-statement© Springer Nature Limited 2024
==== Body
pmcIntroduction

Quantum dots, often referred to as QDs, represent a category of nanoscale semiconductor crystals1. Carbon-based substances like graphene have the potential to be utilized in the creation of Quantum Dots, leading to the formation of graphene quantum dots (GQDs)2. GQDs are defined as zero-dimensional carbon nanomaterials, have excellent fluorescence emission properties, and show excellent characteristics distinguished from conventional semiconductor quantum dots for their low cytotoxicity, good resistance to photobleaching, and excellent biocompatibility3–5. The development and understanding of GQDs have progressed significantly since their discovery. Various synthesis methods have been explored, including the one-step hydrothermal or solvent thermal processes, which are common despite their high temperature (over 180 °C) and long duration requirements that often result in the pyrolysis and polymerization of functional groups6,7. Alternative methods such as chemical vapor deposition, microwave-assisted synthesis, and electrochemical methods have also been investigated to optimize the properties and functionalities of GQDs8. Each synthesis method offers distinct advantages and challenges, contributing to the ongoing refinement of GQD production techniques. For instance, Liu et al. reported on the use of chemical vapor deposition for the synthesis of high-quality GQDs, which provided enhanced control over size and surface properties9.

Functionalization is a crucial approach for enhancing the surface characteristics and overall performance of GQDs10,11. By modifying the surface of GQDs, their applicability in various fields can be significantly improved. In recent years, amino acid-functionalized GQDs have shown a great attention in various applications12,13. This amino acid is uncomplicated, featuring amine and carboxyl groups attached to a carbon atom. Glycine was the first amino acid to be isolated from the hydrolysis of protein by Henri Braconnot in 182014,15. It could be used to functionalize GQDs for environmental applications. In this sense, a facile post-modification method has been developed for the fabrication of glycine-functionalized graphene quantum dots (Gly-GQDs). The prepared Gly-GQDs showed efficient application for the determination of Hg2+ in fresh water16. Moreover, understanding how different conformations of glycine influence its interaction with GQDs is crucial for a comprehensive analysis of these complexes. Glycine can adopt various conformations due to its flexibility around the C-N bond17. These conformations can affect how glycine interacts with GQDs and consequently influence the properties of the GQD–glycine complexes18. In fact, based on the low cytotoxicity and chemical inertia of functionalized GQDs, they have several environmental applications. Dopamine-functionalized GQDs could be used as graphene quantum dots for successive detection of nanomolar ferric ions19. Gautam et al. demonstrated the use of GQDs functionalized with polyethylene glycol (PEG) for targeted drug delivery, showcasing their potential in therapeutic applications20.

GQDs could be further enhanced with Rhodamine to be used for the possible detection of Fe3+ in cancer stem cells21. This application paves the way toward applications of Rhodamine/GQDs in the field of bioimaging. Another way to apply GQDs in the field of bioimaging could be as AuNPs/glycine/GQDs composites with tunable bi-functionalities for cellular imaging22. Furthermore, Facile preparation was used for novel PEG-functionalized QDs with glycine-enhanced fluoroimmunoassays used to detect hazardous AFB1 in medicinal herbs23. Based on the phenomena of quantum confinement, the density of sp2 sites, and edge effects contribute to the unusual photoluminescence properties of GQDs, which makes them the best candidate for huge applications that could be summarized as biomarkers, drug delivery, bioimaging, biosensors, biolabeling, therapeutics, neuroscience, batteries, fuel cells, supercapacitors, electrochemical sensors, etc24–28. For example, Wang et al. successfully employed GQDs for in vivo bioimaging, highlighting their biocompatibility and effectiveness in tracking cellular processes29.

Computational methods, particularly quantum mechanical calculations and molecular modeling, are essential for investigating the electronic, physical, chemical, and biological properties of functionalized materials, including functionalized GQDs30–32. These techniques have been employed to study various nanoscale materials, providing valuable insights into their potential applications in biomedicine and other fields33,34. As mentioned earlier, the division of a graphene sheet into smaller clusters resulted in the identification of four distinct types of Graphene Quantum Dots (GQDs). These were classified as follows: hexagonal with armchair termination, referred to as AHEX; hexagonal with zigzag termination, termed ZHEX; triangular with zigzag termination, labeled ZTRI; and triangular GQD with armchair termination, known as ATRI35. It was also demonstrated that the shape and the imbalance in the number of atoms in GQDs lead to the existence of zero-energy states, and this shape is correlated with both the total and local magnetic moments36. A fluorescence sensor using glucosaminic acid/GQDs was prepared to be applied as it has high selectivity and sensitivity for lactose detection. Density functional theory (DFT) was used to elucidate the mechanism and confirm the experimental findings37.

The present work is conducted to study four types of glycine edge functionalized GQDs (AHEX; ZTRI; ZHEX and ATRI). Total dipole moment, HOMO/LUMO energy gap, and Molecular electrostatic potential MESP were calculated at B3LYP/6-31g(d,p). The reactivity was measured by global reactivity and QSAR descriptors. The most reactive type of GQDs will be further interacted through edge with cellulose, chitosan and sodium alginate. Some descriptors will be presented for the studied structures.

Computational methodology and justification

The model molecules were optimized using the Gaussian 09 (G09) software package38, implemented at the molecular modeling and spectroscopy laboratory, centre of excellence for advanced science, national research centre (NRC), Egypt. The optimization was performed using density functional theory (DFT) with the B3LYP functional and the 6-31G(d,p) basis set39–41. This level of theory was selected for its balance between accuracy and computational efficiency, and it is well-established for predicting molecular geometries and electronic properties. Subsequently, molecular properties such as the total dipole moment, HOMO/LUMO energy gap, and molecular electrostatic potential (MESP) were computed using the same DFT/6-31G(d,p) method. These properties are crucial for understanding the reactivity and interaction potentials of the model molecules. Although the DFT/B3LYP method is generally reliable for these calculations, it may have limitations in accurately predicting weak interactions, which are inherently more challenging to model. This method was chosen due to its wide application in the literature and its efficacy in providing insights into molecular behavior42.

To compute global reactivity indices such as electron affinity (A), ionization energies (I), electrophilicity index (ω), nucleophilicity index (ε), chemical potential (μ), electronegativity (χ), hardness (η), and softness (S), we applied Koopmans’ theorem in conjunction with frontier molecular orbitals using the Spartan software, employing the 6-31+G** basis set43. The descriptors were selected based on their established use in predicting reactivity trends in molecular systems. For quantitative structure-activity relationship (QSAR) analysis, we examined the effects of chemical structure on interactions with cellulose, chitosan, and sodium alginate. Parameters such as accessible surface area (Acc. Area), polar surface area (PSA), accessible polar surface area (Acc. P-area), and electrostatic potentials (Min ElPot and Max ElPot) were calculated using SCIGRESS 0.3 and the PM6 semiempirical method44. These QSAR calculations were instrumental in exploring the interaction dynamics of the ZTRI/glycine composite with the biomaterials. The Quantum Theory of Atoms in Molecules (QTAIM) analysis was performed on the examined structures to further investigate the interactions between graphene quantum dots and the biomaterials. This analysis was conducted using the "output=wfn" command in the Gaussian software, with visualization of the results facilitated by Avogadro software45.

The chosen computational methods, including DFT/B3LYP for electronic properties and semiempirical methods for QSAR analysis, were selected for their reliability and common use in similar studies. However, these methods may not fully capture weak interactions, and the study's focus on four specific types of graphene quantum dots (GQDs) and their interactions with glycine and selected biomaterials may not cover the full range of GQD properties. Future research should explore a broader range of GQD types and their interactions with different amino acids. To improve accuracy, additional computational methods, such as higher-level ab initio calculations or dispersion-corrected DFT, should be considered, alongside comparative studies at different theoretical levels. Further investigations will also examine the impact of glycine conformations on GQD properties.

Results and discussions

Building model molecules

In this study, four types of graphene quantum dots (GQDs) were investigated: AHEX, ZTRI, ZHEX, and ATRI, as depicted in Figure 1a–d, respectively. Glycine was studied for its interaction with each GQD type, hypothesized to form GQD–amino acid complexes through edge interactions. This approach is consistent with the findings of Wang et al., who demonstrated that the edge sites of GQDs play a crucial role in interaction with small molecules, highlighting their potential for forming stable complexes46. For each optimized structure, several key physical parameters were calculated: the total dipole moment (TDM), the HOMO/LUMO energy gap, and the molecular electrostatic potential (MESP). Based on the physical parameters and their comparison with previous research, the most reactive GQD composite was selected for further interaction studies with biomaterials such as cellulose, chitosan, and sodium alginate.Fig. 1 Studied graphene quantum dots GQD whereas (a) AHEX; (b) ZTRI; (c) ZHEX and (d) ATRI.

Calculated physical parameters

The physical parameters calculated include the total dipole moment (TDM), HOMO/LUMO energy gap, and molecular electrostatic potential (MESP), which are critical for assessing the reactivity and stability of the GQD–glycine complexes. The TDM measures the separation of positive and negative charges within a molecule, reflecting its polarity and potential for interaction with other molecules47. According to the findings presented in Table 1, the calculated TDMs for the pure GQDs AHEX, ZTRI, ZHEX, and ATRI were 0.000 Debye, indicating no significant dipole moment for these GQDs in their pure form.Table 1 B3LYP/6-31g(d,p) calculated total dipole moment (TDM) as Debye; HOMO/LUMO energy gap (∆E) as eV for the studied GQDs with their glycine composite.

Structure	TDM (Debye)	∆E (eV)	
AHEX	0.000	3.589	
AHEX/glycine	3.593	3.396	
ZTRI	0.000	0.322	
ZTRI/glycine	4.535	0.323	
ZHEX	0.000	2.821	
ZHEX/glycine	4.189	2.714	
ATRI	0.000	3.193	
ATRI/glycine	4.301	3.071	

The HOMO/LUMO gap is a key indicator of a material’s electronic properties and reactivity. A smaller HOMO/LUMO gap implies a higher tendency for electron transfer processes, which is essential for chemical reactivity48. The HOMO/LUMO gaps for GQDs were as follows: 3.589 eV (AHEX), 0.322 eV (ZTRI), 2.821 eV (ZHEX), and 3.193 eV (ATRI). Previous research supports the notion that an increased TDM and a reduced HOMO/LUMO energy gap enhance a compound's reactivity. For example, Lee et al. (2021) found that GQDs with a higher TDM exhibited greater interaction potentials with surrounding media. Similarly, Kondratenko et al. demonstrated that a lower HOMO/LUMO energy gap correlates with increased reactivity in carbon-based nanomaterials49. Upon interaction with glycine, the total dipole moments of the GQD–glycine composites increased, and the HOMO/LUMO energy gaps decreased. Specifically, the ZTRI/glycine composite showed a TDM of 4.535 Debye and a HOMO/LUMO energy gap of 0.323 eV, as reported in Table 1. This significant increase in TDM and the substantial decrease in the HOMO/LUMO energy gap suggest that ZTRI/glycine is the most reactive composite among the four studied. The increased reactivity of ZTRI/glycine can be attributed to its enhanced ability to interact with surrounding media, as indicated by its high TDM and low energy gap. Additionally, The TDM varied significantly with different glycine conformations. For instance, Mahmud et al. found that the zwitterionic form of glycine exhibited higher dipole moments when interacting with GQDs compared to its neutral form50. This is attributed to the presence of both positive and negative charges in the zwitterionic state, which enhances the overall dipole of the complex.

The HOMO/LUMO energy gap calculations, shown in Figures 2a, 3a, 4a and 5a, reveal that the ZTRI type exhibits the highest dipole moment, suggesting a greater potential for reactivity compared to the other GQD types. This observation is in agreement with the results reported by Sebastian et al., who noted that a higher dipole moment often correlates with increased reactivity in GQD-based systems51. The analysis of the HOMO/LUMO energy gap for the proposed complexes reveals that ZTRI/glycine has the lowest energy gap (as depicted in Figures 2c, 3c, 4c, and 5c), suggesting it is most prone to facilitate electron transfer processes. This observation is consistent with Henna et al. who found that a reduced energy gap in GQDs can improve their electronic interactions with biomolecules52. Additionally, various studies reveal that different glycine conformations impact the HOMO/LUMO energy gap of the GQD–glycine complexes. Larijani et al. also observed that the zwitterionic form of glycine typically results in a lower HOMO/LUMO gap, indicating heightened reactivity53.Fig. 2 B3LYP/6-31g (d, p) calculated (a) HOMO/LUMO energy gap for AHEX; (b) MESP for AHEX; (c) HOMO/LUMO energy gap for AHEX/glycine and (d) MESP for AHEX/glycine.

Fig. 3 B3LYP/6-31g (d, p) calculated (a) HOMO/LUMO energy gap for AHEX; (b) MESP for ZTRI; (c) HOMO/LUMO energy gap for ZTRI/glycine and (d) MESP for ZTRI/glycine.

Fig. 4 B3LYP/6-31g (d, p) calculated (a) HOMO/LUMO energy gap for AHEX; (b) MESP for ZHEX; (c) HOMO/LUMO energy gap for ZHEX/glycine and (d) MESP for ZHEX/glycine.

Fig. 5 B3LYP/6-31g(d,p) calculated (a) HOMO/LUMO energy gap for ATRI; (b) MESP for ATRI; (c) HOMO/LUMO energy gap for ATRI/glycine and (d) MESP for ATRI/glycine.

Molecular electrostatic potential (MESP) provides insight into the electrostatic environment around a molecule, indicating regions of positive or negative potential54. The MESP maps for each GQD and its glycine composite are illustrated in Figures 2b,d up to 5b,d. The MESP is represented in a color scheme where yellow indicates neutrality, neither positive nor negative. The GQDs in their neutral forms are shown in yellow, while the glycine interaction results in a more uniform potential distribution across the GQD surfaces. The MESP data highlight that the ZTRI type exhibits a uniform MESP both before and after interaction with glycine. This uniformity suggests that ZTRI maintains consistent electrostatic interactions, making it a suitable candidate for further studies. This observation is supported by the findings of Ibrahim et al., who reported that uniform MESP can enhance interaction with other biomolecules55. The ZTRI/glycine composite was selected for further interaction studies with biomaterials such as cellulose, chitosan, and sodium alginate. Figure 6a–c illustrates the interactions of the ZTRI/glycine complex with these biomaterials, respectively. The glycine interacts at one edge of the ZTRI structure, while the biomaterials interact at the opposite edge.Fig. 6 Model molecules for ZTRI/glycine with (a) cellulose, (b) chitosan and (c) sodium alginate.

Figure 7a–c presents the mapped HOMO/LUMO energy gaps for ZTRI/glycine interacting with cellulose, chitosan, and sodium alginate, respectively. The HOMO/LUMO mapping in Figure 7 demonstrates that ZTRI/glycine exhibits uniform distribution of HOMO and LUMO orbitals across the ZTRI surface for both ZTRI/glycine/cellulose and ZTRI/glycine/chitosan interactions. This uniform distribution suggests stable interactions with these biomaterials. Figure 8a–c shows the MESP for ZTRI/glycine interacting with the same biomaterials. The MESP maps reveal a uniform potential in the center of the ZTRI structure (yellow). Edges close to the biopolymer show a red color, indicating its ability for further interaction throughout the edge, which is an indication of the ability of the biopolymer to enhance the ZTIR structure throughout the ring near the edge. The decreased TDM and ΔE for sodium alginate suggest that while the interaction is strong, it is less uniform compared to cellulose and chitosan.Fig. 7 HOMO/LUMO energy gap for ZTRI/glycine with (a) cellulose, (b) chitosan and (c) sodium alginate.

Fig. 8 Molecular electrostatic potential MESP for ZTRI/glycine with (a) cellulose, (b) chitosan and (c) sodium alginate.

Table 2 presents the B3LYP/6-31G(d,p) calculated values for the total dipole moment (TDM) and HOMO/LUMO energy gap (ΔE) for the ZTRI/glycine composite interacting with cellulose, chitosan, and sodium alginate. For the ZTRI/glycine composite interacting with cellulose, the TDM was found to be 3.523 Debye, and the HOMO/LUMO energy gap was 5.663 eV. These values suggest a moderate reactivity. In contrast, for the interaction with chitosan, the TDM decreased to 1.151 Debye, and ΔE was 4.753 eV, indicating a reduction in reactivity. When interacting with sodium alginate, the TDM was 3.627 Debye and ΔE was 1.647 eV, showing a variable reactivity depending on the biomaterial. Notably, the TDM for the ZTRI/glycine composite itself was 4.535 Debye with a reduced ΔE of 0.323 eV, suggesting high reactivity. When interacting with cellulose, the TDM decreased to 2.763 Debye, and ΔE increased to 1.264 eV. In the case of ZTRI/glycine/chitosan, the TDM increased to 4.867 Debye, and ΔE decreased to 0.330 eV, indicating enhanced reactivity. For ZTRI/glycine/sodium alginate, the TDM significantly decreased to 8.020 Debye, while ΔE was the lowest at 0.200 eV, suggesting the highest reactivity among the studied composites. The significant variation in TDM and ΔE values among different biomaterials indicates that the interaction strength and reactivity of ZTRI/glycine are highly dependent on the biomaterial used. Based on the values of both TDM and ΔE, the ZTRI/glycine composite interacting with sodium alginate exhibits the highest reactivity among the studied composites. This conclusion is supported by the consistent MESP and HOMO/LUMO mapping results, which indicate strong and stable interactions, particularly with sodium alginate.Table 2 B3LYP/6-31g(d,p) calculated total dipole moment (TDM) as Debye; HOMO/LUMO energy gap (∆E) as eV for the studied ZTRI/glycine composite interacted with cellulose, chitosan and sodium alginate.

Structure	TDM (Debye)	∆E (eV)	
Cellulose	3.523	5.663	
Chitosan	1.151	4.753	
Sodium alginate	3.627	1.647	
ZTRI/glycine	4.535	0.323	
ZTRI/glycine/cellulose	2.763	1.264	
ZTRI/glycine/chitosan	4.867	0.330	
ZTRI/glycine/sodium alginate	8.020	0.200	

Calculated reactivity descriptors

Global reactivity descriptors, indicated how easily the studied molecules loss or gain electrons (ionization potentials and electron affinities) using different methods and a specific set of parameters (at 6–31+G** basis set). The results are presented in Table 3. Ionization energy is a measure of how easily a molecule loses an electron, which is linked to its chemical reactivity. Generally, high ionization energy means a molecule is stable and unreactive, while low ionization energy indicates high reactivity56. In this study, the addition of various materials (cellulose, chitosan, and sodium alginate) to a composite material (ZTRI/glycine) caused changes in its ionization energy (IP). Interestingly, adding sodium alginate increased the calculated IP as shown in Table 3, which suggests it might be more reactive than the other components. This finding is consistent with the work of Domingo et al., who found that increased IP can indicate enhanced reactivity due to the stabilization effects of the added material57.Table 3 Calculated HOMO, LUMO energy, global reactivity descriptors for the studied ZTRI/glycine composite interacted with cellulose, chitosan and sodium alginate using the B3LYP/6-31g(d,p) model.

Structure	LUMO	HOMO	Ionization potential (I)	Electronic affinity (A)	Electronic chemical potential (μ)	Chemical hardness (η)	Absolute softness (S)	Electrophilicity index (ω)	
Cellulose	− 1.46	− 7.12	7.12	− 1.46	− 2.83	4.29	0.233	0.933	
Chitosan	− 1.82	− 6.57	6.57	− 1.82	− 2.38	4.20	0.238	0.672	
Sodium alginate	− 1.28	− 2.93	2.93	1.28	− 2.11	0.83	1.21	2.69	
ZTRI/glycine	− 3.65	− 3.98	3.98	3.65	− 3.81	0.17	2.93	44.10	
ZTRI/glycine/cellulose	− 3.19	− 4.40	4.40	3.19	− 3.80	0.60	0.83	11.90	
ZTRI/glycine/chitosan	− 3.63	− 3.96	3.96	3.63	− 3.80	0.17	2.93	43.64	
ZTRI/glycine/sodium alginate	− 3.90	− 4.19	4.19	3.90	− 4.05	0.15	3.33	56.42	

Electron affinity denotes the ability of a ligand to selectively receive a single electron from a donor58. A positive electron affinity signifies the release of energy upon electron addition, indicating the favorability of the atom or molecule to accept an electron. Conversely, a negative electron affinity implies that energy input is required for electron incorporation into the system. The electron affinities of the ZTRI/glycine composite were calculated in interaction with cellulose, chitosan, and sodium alginate (refer to Table 3). The findings reveal that the ZTRI/glycine composite in interaction with sodium alginate exhibits the highest electron affinity value, while cellulose displays a negative electron affinity value. These observations align with the findings of Kim et al., who demonstrated that higher electron affinity often correlates with better electron acceptance and interaction potential59. The high electron affinity of the ZTRI/glycine/sodium alginate composite implies that it may be more reactive and capable of engaging in electron transfer processes compared to composites with cellulose or chitosan.

The electronic chemical potential (μ) was also determined, which represents the energy needed to add or remove an electron from a system while maintaining constant volume and temperature. Additionally, a molecule characterized by a substantial energy gap is termed "hard," while one with a small energy gap is termed "soft." It's important to note that hard molecules are less polarizable compared to soft ones, as they demand significant energy for excitation60. Utilizing Koopmans' theorem for closed-shell compounds, the electronic chemical potential (μ), chemical hardness (η), and absolute softness (S) can be formally defined.μ=-(I+A)2,

η=1-A2,

S=12η,

where I and A are the ionization potential and electron affinity of the compounds respectively.

Absolute hardness and softness serve as crucial indicators for evaluating the stability and reactivity of molecules. Chemical hardness, in particular, denotes the inherent resistance to the deformation or polarization of the electron cloud within atoms, ions, or molecules when subjected to minor perturbations in chemical reactions. In the present investigation, the ZTRI/glycine composite exhibited a hardness value of 0.17 eV and a chemical potential of -3.81 eV (refer to Table 3). Notably, the hardness value and chemical potential of this composite decreased following its interaction with the suggested molecules, indicating an enhancement in chemical reactivity, particularly in the case of sodium alginate. These findings align with previous studies, such as those by Demircioğlu et al., which demonstrated that a decrease in hardness and chemical potential is associated with enhanced reactivity in molecular systems61.

Parr et al.62 introduced a novel descriptor to quantify the overall electrophilic potency of a compound, termed the electrophilicity index (ω). This index establishes a quantitative classification of a compound's global electrophilic nature. The electrophilicity index (ω) proposed by Parr et al. was designed to gauge the energy reduction resulting from the maximal electron flow between a donor and an acceptor. The definition of the electrophilicity index (ω) by Parr et al. is as followsω=μ22η.

The recent application of this novel reactivity metric has proven instrumental in comprehending the toxicity of diverse pollutants concerning their reactivity and site selectivity. The computed electrophilicity index value characterizes the biological activity of the ZTRI/glycine composite when interacting with cellulose, chitosan, and sodium alginate. In this study, the ZTRI/glycine composite showed varying electrophilicity indices based on its interactions with different biomaterials. Specifically, the ZTRI/glycine/sodium alginate composite exhibited the highest electrophilicity index, reflecting its strong electrophilic character. This result supports the work of Parr et al., who found that a higher electrophilicity index correlates with greater electrophilic potency and reactivity.

Calculated quantitative structure-activity relationship (QSAR) descriptors

QSAR was calculated to examine how the chemical structure of a compound made from ZTRI and glycine affects its interactions with cellulose, chitosan, and sodium alginate. To do this, specific features of the compound, such as accessible surface area (Acc. Area), Polar surface area (PSA), the accessible polar surface area (Acc. P-area), the minimum values of the electrostatic potential (Min ElPot), the maximum values of the electrostatic potential (Max ElPot), the minimum value of the local ionization potential (Min LocionPot), were calculated. These features are like measurable characteristics that help describe the ZTRI/glycine composite's interaction abilities. The QSAR outcomes for the recommended compounds are documented in Table 4.Table 4 QSAR descriptors calculated at B3LYP/6-31G(d, p) for the studied ZTRI/glycine composite interacted with cellulose, chitosan and sodium alginate.

Structure	Volume (Å3)	Acc. Area (Å2)	(PSA) (Å2)	Acc. P-area (Å2)	Min ElPot (KJ/mol)	Max ElPot (KJ/mol)	Min LocionPot (KJ/mol)	
Cellulose	158.13	112.67	65.28	50.00	− 182.65	263.00	39.99	
Chitosan	161.42	115.51	78.34	56.23	− 187.34	220.62	34.52	
Sodium alginate	154.97	140.44	103.91	80.73	− 317.15	551.99	36.60	
ZTRI/glycine	625.90	430.95	56.68	42.31	− 215.76	118.42	29.51	
ZTRI/glycine/cellulose	781.87	508.09	131.82	95.24	− 205.99	272.95	19.94	
ZTRI/glycine/chitosan	786.35	514.62	121.24	86.03	− 218.64	223.90	29.49	
ZTRI/glycine/sodium alginate	781.17	544.97	131.97	97.78	− 303.67	565.27	28.72	

A significant rise in the volume of the ZTRI/glycine composite was noticed when cellulose, chitosan, and sodium alginate were introduced. This alteration encourages us to explore potential interactions or impacts arising from the incorporation of these additional compounds into the ZTRI/glycine composite. The term "Acc. Area" pertains to the portion of a molecule's surface accessible to solvent molecules, considering its three-dimensional structure and the space available for solvent occupancy. Acc. Area calculations are commonly employed to forecast properties such as solubility and interactions with other molecules63. The enrichment of QSAR dataset with supplementary molecules for the ZTRI/glycine composite has revealed a substantial increase in Acc. Area. This interesting observation prompts a more in-depth investigation into the molecular dynamics and interactions underlying this expansion. The heightened accessible surface area indicates a broader molecular exposure of the ZTRI/glycine composite to its surroundings upon the addition of cellulose, chitosan, and sodium alginate. This could potentially influence intermolecular interactions and reactivity.

The polar surface area (PSA) specifically denotes the surface area of a molecule occupied by polar atoms64. On the other hand, the Acc. P area combines the concepts of accessible surface area and polar surface area, representing the portion of a molecule's surface area that is both accessible to solvent molecules and occupied by polar atoms65. Our QSAR results have revealed a significant increase in both PSA and Acc. P area for the ZTRI/glycine composite, particularly evident when incorporating the suggested molecules, especially in the case of ZTRI/glycine/sodium alginate. This noteworthy discovery underscores the heightened polar character introduced by the additional compounds, suggesting potential modifications in intermolecular interactions. The observed expansion indicates an increased exposure of polar functionalities within the molecular structures of the ZTRI/glycine composite, hinting at potential consequences for intermolecular interactions and the modulation of biological activities.

Electrostatic potential, defined as the electric potential energy per unit charge at a specific point surrounding a molecule, serves as a crucial measure in molecular analysis66. Min ElPot is typically situated in regions abundant in electron density, where a positive test charge experiences attraction. Conversely, Max ElPot is found in regions with electron deficiency, causing repulsion for a positive test charge. The expansion of our QSAR dataset, incorporating additional molecules, has brought about noticeable alterations in both Min ElPot and Max ElPot. This intriguing development indicates shifts in electronic distributions within the molecular structures, hinting at potential changes in the reactivity and intermolecular interactions of the ZTRI/glycine composite following the addition of cellulose, chitosan, and sodium alginate. The local ionization potential, on the other hand, focuses on the energy required to remove an electron from a specific location within a molecule67. Min LocionPot denotes the minimum ionization potential at a specific location within a molecule. A minimum local ionization potential indicates that less energy is required to remove an electron from that specific region compared to neighboring areas. This information is crucial for comprehending the reactivity and chemical behavior of distinct parts of a molecule. The decrease in the minimum local ionization potential of the ZTRI/glycine composite subsequent to the addition of cellulose, chitosan, and sodium alginate prompts a thorough investigation into how the introduced molecules contribute to the adjustment of electron affinities within our dataset and the potential implications for the predictive accuracy of our QSAR model.

DOS and QTAIM analyses

The Density of States (DOS) and Quantum Theory of Atoms in Molecules (QTAIM) analyses provide significant insights into the electronic properties and molecular interactions within the studied systems. Figure 9 illustrates the DOS for the investigated structures: Figure 9a corresponds to ZTRI, Figure 9b to ZTRI/glycine, Figure 9c to ZTRI/glycine/cellulose, Figure 9d to ZTRI/glycine/chitosan, and Figure 9e to ZTRI/glycine/sodium alginate.Fig. 9 Density of states (DOS) analysis for (a) ZTRI, (b) ZTRI/glycine, (c) ZTRI/glycine/cellulose, (d) ZTRI/glycine/chitosan, and (e) ZTRI/glycine/sodium alginate.

The DOS analysis shows the number of allowable states or modes per unit of energy for these structures. Notably, the HOMO levels were pushed closer to the Fermi level, indicating stronger molecular interactions between ZTRI and the biomolecules. This shift suggests an increased probability of electron transfer, as observed in similar studies, where graphene-based systems showed significant electronic reconfiguration upon interaction with biomolecules. For instance, in graphene/sodium alginate systems, the highest contribution to the molecular orbitals is attributed to sodium alginate, while carbon atoms exhibit the lowest contribution68. This pattern is consistent with our findings, where sodium alginate, compared to cellulose and chitosan, induces a more pronounced electron redistribution upon interacting with graphene. This redistribution is crucial for understanding the molecular reactivity and stability of the composites.

QTAIM, a well-established methodology, provides detailed insights into the electronic density distribution, identifying bond paths and critical points that correspond to both bonds and bond orders69. In addition, it is a valuable tool for understanding adsorption processes and predicting the behavior of different molecules on various surfaces70. Within QTAIM analysis, the electron density at bond critical points (BCPs) between interacting atoms is essential for determining the strength of bonding interactions71. Higher electron density values at these critical points generally indicate stronger electronic charge densities, which correspond to more robust and covalent interactions. Additionally, if ∇2ρ(r) is less than 0 and H(r) is less than 0, it suggests a covalent (shared) interaction. In contrast, when ∇2ρ(r) is greater than 0 and H(r) is greater than 0, it points to non-covalent (closed-shell) interactions, such as weak hydrogen bonds, van der Waals forces, and electrostatic interactions. As illustrated in Figure 10, QTAIM analysis reveals the nature of non-covalent interactions within the studied structures. The analysis shows that ZTRI/glycine/sodium alginate (Figure 10e) is more stable than ZTRI/glycine/cellulose (Figure 10c) and ZTRI/glycine/chitosan (Figure 10d) structures. This stability is linked to stronger hydrogen bonding and van der Waals interactions, which are supported by higher values of electron density (ρ) and Laplacian of electron density (∇2ρ) at bond critical points, indicating stronger intermolecular forces.Fig. 10 QTAIM analysis for (a) ZTRI, (b) ZTRI/glycine, (c) ZTRI/glycine/cellulose, (d) ZTRI/glycine/chitosan, and (e) ZTRI/glycine/sodium alginate.

The increased stability of the ZTRI/glycine/sodium alginate system aligns with previous findings where edge-functionalized graphene showed enhanced reactivity when blended with sodium alginate, compared to other polysaccharides72. This is due to sodium alginate’s ability to stabilize the composite through multiple non-covalent interactions, such as electrostatic interactions and hydrogen bonding, which are more prominent in the sodium alginate structure. Additionally, our results show that non-covalent interactions between ZTRI and glycine (Figure 10b) are significant, indicating a substantial role of glycine in modulating the overall electronic environment of the composite. In summary, the DOS and QTAIM analyses highlight the impact of molecular interactions on the electronic structure and stability of the composites. The findings underline the importance of selecting suitable biomolecules, such as sodium alginate, to enhance the properties of graphene-based materials for potential applications.

Conclusion

The current computational investigation provides a comprehensive investigation of the interactions between four types of graphene quantum dots (GQDs)—AHEX, ZTRI, ZHEX, and ATRI—and glycine, with further interactions involving biomaterials such as cellulose, chitosan, and sodium alginate. Key physical parameters, including total dipole moment (TDM), HOMO/LUMO energy gap, and molecular electrostatic potential (MESP), were calculated for each GQD and its glycine complexes. The results indicate that the ZTRI/glycine composite exhibits the highest reactivity, as evidenced by its significant TDM increase to 4.535 Debye and a reduction in the HOMO/LUMO energy gap to 0.323 eV. This high reactivity is further supported by consistent and uniform MESP mapping, suggesting strong interaction potential with biomaterials. The ZTRI/glycine composite's interactions with cellulose, chitosan, and sodium alginate were examined, with sodium alginate showing the highest reactivity, indicated by the lowest HOMO/LUMO energy gap of 0.200 eV and a TDM of 8.020 Debye. Further analysis of global reactivity descriptors revealed that the ZTRI/glycine composite's interaction with sodium alginate leads to enhanced reactivity. QSAR descriptors also demonstrated an increase in accessible surface area (Acc. Area), polar surface area (PSA), and electrostatic potential, particularly with sodium alginate, highlighting the potential for strong intermolecular interactions.

The density of states (DOS) analysis revealed that the contributions to molecular orbitals varied among the studied structures, with the most significant contributions from the biomolecules, aligning with previous observations in graphene/sodium alginate systems. Quantum theory of atoms in molecules (QTAIM) analysis provided further insights, showing that the ZTRI/glycine/sodium alginate complex was more stable than the corresponding complexes with cellulose or chitosan. This suggests that blending edge-functionalized graphene with sodium alginate enhances reactivity more effectively than with other polysaccharides. Future research will extend these findings by exploring a broader spectrum of GQD types and glycine conformations, employing additional computational methods for verification, and conducting experimental validation through spectroscopy or microscopy. This will help to further elucidate the impact of various modifications on GQD reactivity and interactions with biomolecules, ultimately tailoring specific properties for diverse applications. In conclusion, this study underscores the significant influence of glycine conformations on GQD properties, laying the groundwork for future explorations and applications of functionalized GQDs in various fields.

Acknowledgements

This paper is based upon work supported by Science; Technology & Innovation Funding Authority (STDF) under a grant (47336) entitled “Eco-Friendly Cost-Effective Microsphere for Multiple Applications”

Author contributions

Authors are equally participated in work, writing and discussion of this manuscript.

Funding

Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Competing interests

The authors declare no competing interests.

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
==== Refs
References

1. Lee JS Youn YH Kwon IK Ko NR Recent advances in quantum dots for biomedical applications J. Pharm. Investig. 2018 48 209 214 10.1007/s40005-018-0387-3
Lee, J. S., Youn, Y. H., Kwon, I. K. & Ko, N. R. Recent advances in quantum dots for biomedical applications. J. Pharm. Investig. 48, 209–214 (2018).
2. Nigam Joshi P Kundu S Sanghi SK Sarkar D graphene quantum dots-from emergence to nanotheranostic applications Smart Drug Deliv. Syst. 2016 7 159 195
Nigam Joshi, P., Kundu, S., Sanghi, S. K. & Sarkar, D. graphene quantum dots-from emergence to nanotheranostic applications. Smart Drug Deliv. Syst. 7, 159–195 (2016).
3. Biswas MC Islam MT Nandy PK Hossain MM Graphene quantum dots (GQDs) for bioimaging and drug delivery applications: A review ACS Mater. Lett. 2021 3 6 889 911 10.1021/acsmaterialslett.0c00550
Biswas, M. C., Islam, M. T., Nandy, P. K. & Hossain, M. M. Graphene quantum dots (GQDs) for bioimaging and drug delivery applications: A review. ACS Mater. Lett. 3(6), 889–911 (2021).
4. Facure MHM Schneider R Mercante LA Correa DS A review on graphene quantum dots and their nanocomposites: From laboratory synthesis towards agricultural and environmental applications Environ. Sci. Nano 2020 7 12 3710 3734 10.1039/D0EN00787K
Facure, M. H. M., Schneider, R., Mercante, L. A. & Correa, D. S. A review on graphene quantum dots and their nanocomposites: From laboratory synthesis towards agricultural and environmental applications. Environ. Sci. Nano 7(12), 3710–3734 (2020).
5. Zhao X Gao W Zhang H Qiu X Luo Y Zhao X Gao W Zhang H Qiu X Luo Y Graphene quantum dots in biomedical applications: recent advances and future challenges Handbook of Nanomaterials in Analytical Chemistry 2020 Elsevier 493 505
Zhao, X., Gao, W., Zhang, H., Qiu, X. & Luo, Y. Graphene quantum dots in biomedical applications: recent advances and future challenges. In Handbook of Nanomaterials in Analytical Chemistry (eds Zhao, X. et al.) 493–505 (Elsevier, 2020).
6. Ju J Chen W Synthesis of highly fluorescent nitrogen-doped graphene quantum dots for sensitive, label-free detection of Fe (III) in aqueous media Biosens. Bioelectron. 2014 58 219 225 10.1016/j.bios.2014.02.061 24650437
Ju, J. & Chen, W. Synthesis of highly fluorescent nitrogen-doped graphene quantum dots for sensitive, label-free detection of Fe (III) in aqueous media. Biosens. Bioelectron. 58, 219–225 (2014).24650437
7. Van Tam T Trung NB Kim HR Chung JS Choi WM One-pot synthesis of N-doped graphene quantum dots as a fluorescent sensing platform for Fe3+ ions detection Sens. Actuators B Chem. 2014 202 568 573 10.1016/j.snb.2014.05.045
Van Tam, T., Trung, N. B., Kim, H. R., Chung, J. S. & Choi, W. M. One-pot synthesis of N-doped graphene quantum dots as a fluorescent sensing platform for Fe3+ ions detection. Sens. Actuators B Chem. 202, 568–573 (2014).
8. Sheikh Mohd Ghazali SAI Fatimah I Zamil ZN Zulkifli NN Adam N Graphene quantum dots: A comprehensive overview Open Chem. 2023 21 1 20220285 10.1515/chem-2022-0285
Sheikh Mohd Ghazali, S. A. I., Fatimah, I., Zamil, Z. N., Zulkifli, N. N. & Adam, N. Graphene quantum dots: A comprehensive overview. Open Chem. 21(1), 20220285 (2023).
9. Liu D Raman enhancement on ultra-clean graphene quantum dots produced by quasi-equilibrium plasma-enhanced chemical vapor deposition Nat. Commun. 2018 9 1 193 10.1038/s41467-017-02627-5 29335471
Liu, D. et al. Raman enhancement on ultra-clean graphene quantum dots produced by quasi-equilibrium plasma-enhanced chemical vapor deposition. Nat. Commun. 9(1), 193 (2018).29335471
10. Liu H Lysosome-targeted carbon dots for ratiometric imaging of formaldehyde in living cells Nanoscale 2019 11 17 8458 8463 10.1039/C9NR01678C 30994690
Liu, H. et al. Lysosome-targeted carbon dots for ratiometric imaging of formaldehyde in living cells. Nanoscale 11(17), 8458–8463 (2019).30994690
11. Qu C Zhang D Yang R Hu J Qu L Nitrogen and sulfur co-doped graphene quantum dots for the highly sensitive and selective detection of mercury ion in living cells Spectrochim. Acta A Mol. Biomol. Spectrosc. 2019 206 588 596 10.1016/j.saa.2018.07.097 30196152
Qu, C., Zhang, D., Yang, R., Hu, J. & Qu, L. Nitrogen and sulfur co-doped graphene quantum dots for the highly sensitive and selective detection of mercury ion in living cells. Spectrochim. Acta A Mol. Biomol. Spectrosc. 206, 588–596 (2019).30196152
12. Ravi PV Subramaniyam V Pattabiraman A Pichumani M Do amino acid functionalization stratagems on carbonaceous quantum dots imply multiple applications? A comprehensive review RSC Adv. 2021 11 55 35028 35045 10.1039/D1RA05571B 35494767
Ravi, P. V., Subramaniyam, V., Pattabiraman, A. & Pichumani, M. Do amino acid functionalization stratagems on carbonaceous quantum dots imply multiple applications? A comprehensive review. RSC Adv. 11(55), 35028–35045 (2021).35494767
13. Yu T Structure-performance relationships between amino acid-functionalized graphene quantum dots and self-cleaning nanofiltration membranes J. Memb. Sci. 2022 644 120068 10.1016/j.memsci.2021.120068
Yu, T. et al. Structure-performance relationships between amino acid-functionalized graphene quantum dots and self-cleaning nanofiltration membranes. J. Memb. Sci. 644, 120068 (2022).
14. Sparkman OD Penton Z Kitson FG Gas Chromatography and Mass Spectrometry: A Practical Guide 2011 Academic press
Sparkman, O. D., Penton, Z. & Kitson, F. G. Gas Chromatography and Mass Spectrometry: A Practical Guide (Academic press, 2011).
15. Aliyu HN Na’Aliya J Potentiometric studies on essential metal (II) amino acid complexes Int. Res. J. Pharm. Pharmacol. 2012 2 2 76 80
Aliyu, H. N. & Na’Aliya, J. Potentiometric studies on essential metal (II) amino acid complexes. Int. Res. J. Pharm. Pharmacol. 2(2), 76–80 (2012).
16. Zhu Q A glycine-functionalized graphene quantum dots synthesized by a facile post-modification strategy for a sensitive and selective fluorescence sensor of mercury ions Spectrochim. Acta A Mol. Biomol. Spectrosc. 2021 247 119090 10.1016/j.saa.2020.119090 33137626
Zhu, Q. et al. A glycine-functionalized graphene quantum dots synthesized by a facile post-modification strategy for a sensitive and selective fluorescence sensor of mercury ions. Spectrochim. Acta A Mol. Biomol. Spectrosc. 247, 119090 (2021).33137626
17. Sherman SL Fischer KC Garand E Conformational changes induced by methyl side-chains in protonated tripeptides containing glycine and alanine residues J. Phys. Chem. A 2022 126 25 4036 4045 10.1021/acs.jpca.2c02584 35700447
Sherman, S. L., Fischer, K. C. & Garand, E. Conformational changes induced by methyl side-chains in protonated tripeptides containing glycine and alanine residues. J. Phys. Chem. A 126(25), 4036–4045 (2022).35700447
18. Raut J N-carbon quantum dot/Cu complex for in vivo monitoring of glycine levels ACS Appl. Nano Mater. 2023 6 24 23611 23619 10.1021/acsanm.3c05401
Raut, J. et al. N-carbon quantum dot/Cu complex for in vivo monitoring of glycine levels. ACS Appl. Nano Mater. 6(24), 23611–23619 (2023).
19. Dutta Chowdhury A Doong R Highly sensitive and selective detection of nanomolar ferric ions using dopamine functionalized graphene quantum dots ACS Appl. Mater. Interfaces 2016 8 32 21002 21010 10.1021/acsami.6b06266 27472083
Dutta Chowdhury, A. & Doong, R. Highly sensitive and selective detection of nanomolar ferric ions using dopamine functionalized graphene quantum dots. ACS Appl. Mater. Interfaces 8(32), 21002–21010 (2016).27472083
20. Gautam A Pal K Gefitinib conjugated PEG passivated graphene quantum dots incorporated PLA microspheres for targeted anticancer drug delivery Heliyon 2022 10.1016/j.heliyon.2022.e12512 36619399
Gautam, A. & Pal, K. Gefitinib conjugated PEG passivated graphene quantum dots incorporated PLA microspheres for targeted anticancer drug delivery. Heliyon10.1016/j.heliyon.2022.e12512 (2022).36619399
21. Guo R Zhou S Li Y Li X Fan L Voelcker NH Rhodamine-functionalized graphene quantum dots for detection of Fe3+ in cancer stem cells ACS Appl. Mater. Interfaces 2015 7 43 23958 23966 10.1021/acsami.5b06523 26317667
Guo, R. et al. Rhodamine-functionalized graphene quantum dots for detection of Fe3+ in cancer stem cells. ACS Appl. Mater. Interfaces 7(43), 23958–23966 (2015).26317667
22. Liu J Qin L Kang S-Z Li G Li X Gold nanoparticles/glycine derivatives/graphene quantum dots composite with tunable fluorescence and surface enhanced Raman scattering signals for cellular imaging Mater. Des. 2017 123 32 38 10.1016/j.matdes.2017.02.083
Liu, J., Qin, L., Kang, S.-Z., Li, G. & Li, X. Gold nanoparticles/glycine derivatives/graphene quantum dots composite with tunable fluorescence and surface enhanced Raman scattering signals for cellular imaging. Mater. Des. 123, 32–38 (2017).
23. Zhang L Facile preparation of stable PEG-functionalized quantum dots with glycine-enhanced photoluminescence and their application for screening of aflatoxin B1 in herbs Sens. Actuators B Chem. 2018 261 188 195 10.1016/j.snb.2018.01.124
Zhang, L. et al. Facile preparation of stable PEG-functionalized quantum dots with glycine-enhanced photoluminescence and their application for screening of aflatoxin B1 in herbs. Sens. Actuators B Chem. 261, 188–195 (2018).
24. Zhu S Tang S Zhang J Yang B Control the size and surface chemistry of graphene for the rising fluorescent materials Chem. Commun. 2012 48 38 4527 4539 10.1039/c2cc31201h
Zhu, S., Tang, S., Zhang, J. & Yang, B. Control the size and surface chemistry of graphene for the rising fluorescent materials. Chem. Commun. 48(38), 4527–4539 (2012).
25. Zhang, X., Wang, J. and Yang, G. Application of graphene quantum dots in medical and pharmaceutical analyses. In The World Scientific Encyclopedia of Nanomedicine and Bioengineering II: Bioimplants, Regenerative Medicine, and Nano-Cancer Diagnosis and Phototherapy Volume 1: Synthesis and Biomedical Applications of Graphene Quantum Dots, pp. 57–76 (World Scientific, 2017).
26. Ramezani M Ramezani M Graphene-based hybrid nanomaterials for biomedical applications Biomedical Applications of Graphene and 2D Nanomaterials 2019 Elsevier 119 141
Ramezani, M. et al. Graphene-based hybrid nanomaterials for biomedical applications. In Biomedical Applications of Graphene and 2D Nanomaterials (eds Ramezani, M. et al.) 119–141 (Elsevier, 2019).
27. Shang L Synergistic effect of oxygen-and nitrogen-containing groups in graphene quantum dots: Red emitted dual-mode magnetic resonance imaging contrast agents with high relaxivity ACS Appl. Mater. Interfaces 2022 14 35 39885 39895 10.1021/acsami.2c12719 36031928
Shang, L. et al. Synergistic effect of oxygen-and nitrogen-containing groups in graphene quantum dots: Red emitted dual-mode magnetic resonance imaging contrast agents with high relaxivity. ACS Appl. Mater. Interfaces 14(35), 39885–39895 (2022).36031928
28. Zhang R Chen W Recent advances in graphene-based nanomaterials for fabricating electrochemical hydrogen peroxide sensors Biosens. Bioelectron. 2017 89 249 268 10.1016/j.bios.2016.01.080 26852831
Zhang, R. & Chen, W. Recent advances in graphene-based nanomaterials for fabricating electrochemical hydrogen peroxide sensors. Biosens. Bioelectron. 89, 249–268 (2017).26852831
29. Chung S Revia RA Zhang M Graphene quantum dots and their applications in bioimaging, biosensing, and therapy Adv. Mater. 2021 33 22 1904362 10.1002/adma.201904362
Chung, S., Revia, R. A. & Zhang, M. Graphene quantum dots and their applications in bioimaging, biosensing, and therapy. Adv. Mater. 33(22), 1904362 (2021).
30. Abdel-Maksoud G Physical prospective of polyamide 6 for the consolidation of fragile vegetable tanned leather artifacts J. Cult. Herit. 2024 67 32 41 10.1016/j.culher.2024.02.002
Abdel-Maksoud, G. et al. Physical prospective of polyamide 6 for the consolidation of fragile vegetable tanned leather artifacts. J. Cult. Herit. 67, 32–41 (2024).
31. Mahmoud AA Khafagy RM Ibrahim MA Investigating the electronic properties of PANI/graphene/PVDF/PTFE nanocomposite Opt. Quantum Electron. 2024 56 4 666 10.1007/s11082-024-06320-y
Mahmoud, A. A., Khafagy, R. M. & Ibrahim, M. A. Investigating the electronic properties of PANI/graphene/PVDF/PTFE nanocomposite. Opt. Quantum Electron. 56(4), 666 (2024).
32. More MP Deshmukh PK Computational studies and biosensory applications of graphene-based nanomaterials: A state-of-the-art review Nanotechnology 2020 31 43 432001 10.1088/1361-6528/ab996e 32498048
More, M. P. & Deshmukh, P. K. Computational studies and biosensory applications of graphene-based nanomaterials: A state-of-the-art review. Nanotechnology 31(43), 432001 (2020).32498048
33. Elhaes H Ezzat HA Ibrahim A Samir M Refaat A Ibrahim MA Spectroscopic, Hartree-Fock and DFT study of the molecular structure and electronic properties of functionalized chitosan and chitosan-graphene oxide for electronic applications Opt. Quantum Electron. 2024 56 3 458 10.1007/s11082-023-05978-0
Elhaes, H. et al. Spectroscopic, Hartree-Fock and DFT study of the molecular structure and electronic properties of functionalized chitosan and chitosan-graphene oxide for electronic applications. Opt. Quantum Electron. 56(3), 458 (2024).
34. Hegazy MA Effect of CuO and graphene on PTFE microfibers: experimental and modeling approaches Polymers (Basel) 2022 14 6 1069 10.3390/polym14061069 35335400
Hegazy, M. A. et al. Effect of CuO and graphene on PTFE microfibers: experimental and modeling approaches. Polymers (Basel) 14(6), 1069 (2022).35335400
35. Abdelsalam H Elhaes H Ibrahim MA First principles study of edge carboxylated graphene quantum dots Phys. B Condens. Matter 2018 537 77 86 10.1016/j.physb.2018.02.001
Abdelsalam, H., Elhaes, H. & Ibrahim, M. A. First principles study of edge carboxylated graphene quantum dots. Phys. B Condens. Matter 537, 77–86 (2018).
36. Fernández-Rossier J Palacios JJ Magnetism in graphene nanoislands Phys. Rev. Lett. 2007 99 17 177204 10.1103/PhysRevLett.99.177204 17995364
Fernández-Rossier, J. & Palacios, J. J. Magnetism in graphene nanoislands. Phys. Rev. Lett. 99(17), 177204 (2007).17995364
37. Zhou C Glucosaminic acid-functionalized graphene quantum dots for sensitive detection of lactose in living cells and real food samples Sens. Actuators B Chem. 2023 381 133441 10.1016/j.snb.2023.133441
Zhou, C. et al. Glucosaminic acid-functionalized graphene quantum dots for sensitive detection of lactose in living cells and real food samples. Sens. Actuators B Chem. 381, 133441 (2023).
38. Frisch, M. J. et al. Gaussian 09, Revision D. 01, Gaussian, Inc., Wallingford CT. See also URL http//www. gaussian.com (2009).
39. Vosko SH Wilk L Nusair M Accurate spin-dependent electron liquid correlation energies for local spin density calculations: A critical analysis Can. J. Phys. 1980 58 8 1200 1211 10.1139/p80-159
Vosko, S. H., Wilk, L. & Nusair, M. Accurate spin-dependent electron liquid correlation energies for local spin density calculations: A critical analysis. Can. J. Phys. 58(8), 1200–1211 (1980).
40. Raghavachari K Perspective on ‘Density functional thermochemistry. III. The role of exact exchange’ Becke AD (1993) J Chem Phys 98: 5648–52 Theor. Chem. Acc. 2000 103 361 363 10.1007/s002149900065
Raghavachari, K. Perspective on ‘Density functional thermochemistry. III. The role of exact exchange’ Becke AD (1993) J Chem Phys 98: 5648–52. Theor. Chem. Acc. 103, 361–363 (2000).
41. Lee C Yang W Parr RG Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density Phys. Rev. B 1988 37 2 785 10.1103/PhysRevB.37.785
Lee, C., Yang, W. & Parr, R. G. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B 37(2), 785 (1988).
42. Koopmans T Über die zuordnung von wellenfunktionen und eigenwerten zu den einzelnen elektronen eines atoms Physica 1934 1 1–6 104 113 10.1016/S0031-8914(34)90011-2
Koopmans, T. Über die zuordnung von wellenfunktionen und eigenwerten zu den einzelnen elektronen eines atoms. Physica 1(1–6), 104–113 (1934).
43. Sandoval-Yañez C Martínez-Araya JI Assessment of a set of twelve density functionals to estimate the global reactivity of myricetin through the Koopmans’ theorem Chem. Phys. Lett. 2019 715 354 359 10.1016/j.cplett.2018.11.056
Sandoval-Yañez, C. & Martínez-Araya, J. I. Assessment of a set of twelve density functionals to estimate the global reactivity of myricetin through the Koopmans’ theorem. Chem. Phys. Lett. 715, 354–359 (2019).
44. SCIGRESS MO-G Version 1.2B, “No Title. Fujitsu Limited, (2013).
45. Hanwell MD Curtis DE Lonie DC Vandermeersch T Zurek E Hutchison GR Avogadro: An open-source molecular builder and visualization tool J. Cheminform. 2012 4 17 10.1186/1758-2946-4-17 22889332
Hanwell, M. D. et al. Avogadro: An open-source molecular builder and visualization tool. J. Cheminform. 4, 17 (2012).22889332
46. Wang S Lemon Z Cole IS Li Q Tailoring the edges of graphene quantum dots to establish localized π–π interactions with aromatic molecules RSC Adv. 2015 5 51 41248 41254 10.1039/C5RA04927J
Wang, S., Lemon, Z., Cole, I. S. & Li, Q. Tailoring the edges of graphene quantum dots to establish localized π–π interactions with aromatic molecules. RSC Adv. 5(51), 41248–41254 (2015).
47. Minkin VI Dipole Moments in Organic Chemistry 2012 Springer Science & Business Media
Minkin, V. I. Dipole Moments in Organic Chemistry (Springer Science & Business Media, 2012).
48. Miar M Shiroudi A Pourshamsian K Oliaey AR Hatamjafari F Theoretical investigations on the HOMO–LUMO gap and global reactivity descriptor studies, natural bond orbital, and nucleus-independent chemical shifts analyses of 3-phenylbenzo [d] thiazole-2 (3 H)-imine and its para-substituted derivatives: Solvent and J. Chem. Res. 2021 45 1–2 147 158 10.1177/1747519820932091
Miar, M., Shiroudi, A., Pourshamsian, K., Oliaey, A. R. & Hatamjafari, F. Theoretical investigations on the HOMO–LUMO gap and global reactivity descriptor studies, natural bond orbital, and nucleus-independent chemical shifts analyses of 3-phenylbenzo [d] thiazole-2 (3 H)-imine and its para-substituted derivatives: Solvent and. J. Chem. Res. 45(1–2), 147–158 (2021).
49. Kondratenko M Stoyanov SR Gusarov S Kovalenko A McCreery RL Theoretical modeling of tunneling barriers in carbon-based molecular electronic junctions J. Phys. Chem. C 2015 119 21 11286 11295 10.1021/jp5128332
Kondratenko, M., Stoyanov, S. R., Gusarov, S., Kovalenko, A. & McCreery, R. L. Theoretical modeling of tunneling barriers in carbon-based molecular electronic junctions. J. Phys. Chem. C 119(21), 11286–11295 (2015).
50. Mahmud, T. Adsorption of oligonucleotides on quantum dots coated with zwitterionic ligands and other water-soluble ligands (2012).
51. Sebastian D Pallikkara A Bhatt H Ghosh HN Ramakrishnan K Unravelling the surface-state assisted ultrafast charge transfer dynamics of graphene quantum dot-based nanohybrids via transient absorption spectroscopy J. Phys. Chem. C 2022 126 27 11182 11192 10.1021/acs.jpcc.2c02170
Sebastian, D., Pallikkara, A., Bhatt, H., Ghosh, H. N. & Ramakrishnan, K. Unravelling the surface-state assisted ultrafast charge transfer dynamics of graphene quantum dot-based nanohybrids via transient absorption spectroscopy. J. Phys. Chem. C 126(27), 11182–11192 (2022).
52. Henna TK Pramod K Graphene quantum dots redefine nanobiomedicine Mater. Sci. Eng. C 2020 110 110651 10.1016/j.msec.2020.110651
Henna, T. K. & Pramod, K. Graphene quantum dots redefine nanobiomedicine. Mater. Sci. Eng. C 110, 110651 (2020).
53. Larijani HT Jahanshahi N Ganji MD Kiani MH Computational studies on the interactions of glycine amino acid with graphene, h-BN and h-SiC monolayers Phys. Chem. Chem. Phys. 2017 19 3 1896 1908 10.1039/C6CP06672K 28004048
Larijani, H. T., Jahanshahi, N., Ganji, M. D. & Kiani, M. H. Computational studies on the interactions of glycine amino acid with graphene, h-BN and h-SiC monolayers. Phys. Chem. Chem. Phys. 19(3), 1896–1908 (2017).28004048
54. Gadre SR Suresh CH Mohan N Electrostatic potential topology for probing molecular structure, bonding and reactivity Molecules 2021 26 11 3289 10.3390/molecules26113289 34072507
Gadre, S. R., Suresh, C. H. & Mohan, N. Electrostatic potential topology for probing molecular structure, bonding and reactivity. Molecules 26(11), 3289 (2021).34072507
55. Ibrahim M Youness RA Taha MA Ikhmayies SJ Overview of some production routes for hydroxyapatite and its applications Advances in Minerals Research 2024 Springer 157 198
Ibrahim, M., Youness, R. A. & Taha, M. A. Overview of some production routes for hydroxyapatite and its applications. In Advances in Minerals Research (ed. Ikhmayies, S. J.) 157–198 (Springer, 2024).
56. El-Sayed N El Bakary M Ibrahim M ELgamal M Molecular modeling analysis of chitosan-dopamine blend with iron oxide nanoparticles for tissue engineering applications Biointerface Res. Appl. Chem. 2021 11 12483 12494 10.33263/BRIAC115.1248312494
El-Sayed, N., El Bakary, M., Ibrahim, M. & ELgamal, M. Molecular modeling analysis of chitosan-dopamine blend with iron oxide nanoparticles for tissue engineering applications. Biointerface Res. Appl. Chem. 11, 12483–12494 (2021).
57. Domingo LR Ríos-Gutiérrez M Pérez P Applications of the conceptual density functional theory indices to organic chemistry reactivity Molecules 2016 21 6 748 10.3390/molecules21060748 27294896
Domingo, L. R., Ríos-Gutiérrez, M. & Pérez, P. Applications of the conceptual density functional theory indices to organic chemistry reactivity. Molecules 21(6), 748 (2016).27294896
58. Meenakshi R Spectral investigations, DFT based global reactivity descriptors, Inhibition efficiency and analysis of 5-chloro-2-nitroanisole as π-spacer with donor-acceptor variations effect for DSSCs performance J. Mol. Struct. 2017 1127 694 707 10.1016/j.molstruc.2016.08.030
Meenakshi, R. Spectral investigations, DFT based global reactivity descriptors, Inhibition efficiency and analysis of 5-chloro-2-nitroanisole as π-spacer with donor-acceptor variations effect for DSSCs performance. J. Mol. Struct. 1127, 694–707 (2017).
59. Kim KC Liu T Jung KH Lee SW Jang SS Unveiled correlations between electron affinity and solvation in redox potential of quinone-based sodium-ion batteries Energy Stor. Mater. 2019 19 242 250
Kim, K. C., Liu, T., Jung, K. H., Lee, S. W. & Jang, S. S. Unveiled correlations between electron affinity and solvation in redox potential of quinone-based sodium-ion batteries. Energy Stor. Mater. 19, 242–250 (2019).
60. Karabacak M Yilan E Molecular structure, spectroscopic (FT-IR, FT-Raman, 13C and 1H NMR, UV), polarizability and first-order hyperpolarizability, HOMO and LUMO analysis of 4′-methylbiphenyl-2-carbonitrile Spectrochim. Acta A Mol. Biomol. Spectrosc. 2012 87 273 285 10.1016/j.saa.2011.11.051 22185952
Karabacak, M. & Yilan, E. Molecular structure, spectroscopic (FT-IR, FT-Raman, 13C and 1H NMR, UV), polarizability and first-order hyperpolarizability, HOMO and LUMO analysis of 4′-methylbiphenyl-2-carbonitrile. Spectrochim. Acta A Mol. Biomol. Spectrosc. 87, 273–285 (2012).22185952
61. Demircioğlu Z Kaştaş ÇA Büyükgüngör O Theoretical analysis (NBO, NPA, Mulliken population method) and molecular orbital studies (hardness, chemical potential, electrophilicity and Fukui function analysis) of (E)-2-((4-hydroxy-2-methylphenylimino) methyl)-3-methoxyphenol J. Mol. Struct. 2015 1091 183 195 10.1016/j.molstruc.2015.02.076
Demircioğlu, Z., Kaştaş, Ç. A. & Büyükgüngör, O. Theoretical analysis (NBO, NPA, Mulliken population method) and molecular orbital studies (hardness, chemical potential, electrophilicity and Fukui function analysis) of (E)-2-((4-hydroxy-2-methylphenylimino) methyl)-3-methoxyphenol. J. Mol. Struct. 1091, 183–195 (2015).
62. Parr RG Szentpaly LV SJJ ot ACS Liu Electrophilicity Index 1999 121 1922 1924
Parr, R. G. & Szentpaly, L. V. SJJ ot ACS Liu. Electrophilicity Index 121, 1922–1924 (1999).
63. Hafsa NE Arndt D Wishart DS Accessible surface area from NMR chemical shifts J. Biomol. NMR 2015 62 387 401 10.1007/s10858-015-9957-0 26078090
Hafsa, N. E., Arndt, D. & Wishart, D. S. Accessible surface area from NMR chemical shifts. J. Biomol. NMR 62, 387–401 (2015).26078090
64. Schaftenaar G de Vlieg J Quantum mechanical polar surface area J. Comput. Aided. Mol. Des. 2012 26 311 318 10.1007/s10822-012-9557-y 22391921
Schaftenaar, G. & de Vlieg, J. Quantum mechanical polar surface area. J. Comput. Aided. Mol. Des. 26, 311–318 (2012).22391921
65. Vistoli G Pedretti A Testa B Molecular fields to assess recognition forces and property spaces Virtual ADMET Assess. Target Sel. Matur. 2006 6 119
Vistoli, G., Pedretti, A. & Testa, B. Molecular fields to assess recognition forces and property spaces. Virtual ADMET Assess. Target Sel. Matur. 6, 119 (2006).
66. Suresh CH Remya GS Anjalikrishna PK Molecular electrostatic potential analysis: A powerful tool to interpret and predict chemical reactivity Wiley Interdiscip. Rev. Comput. Mol. Sci. 2022 12 5 e1601 10.1002/wcms.1601
Suresh, C. H., Remya, G. S. & Anjalikrishna, P. K. Molecular electrostatic potential analysis: A powerful tool to interpret and predict chemical reactivity. Wiley Interdiscip. Rev. Comput. Mol. Sci. 12(5), e1601 (2022).
67. Politzer P Murray JS Bulat FA Average local ionization energy: A review J. Mol. Model. 2010 16 11 1731 1742 10.1007/s00894-010-0709-5 20411398
Politzer, P., Murray, J. S. & Bulat, F. A. Average local ionization energy: A review. J. Mol. Model. 16(11), 1731–1742 (2010).20411398
68. Elhaes H Ibrahim A Osman O Ibrahim MA Molecular modeling analysis for functionalized graphene/sodium alginate composite Sci. Rep. 2024 14 1 14825 10.1038/s41598-024-64698-x 38937511
Elhaes, H., Ibrahim, A., Osman, O. & Ibrahim, M. A. Molecular modeling analysis for functionalized graphene/sodium alginate composite. Sci. Rep. 14(1), 14825 (2024).38937511
69. Bader RFW A quantum theory of molecular structure and its applications Chem. Rev. 1991 91 5 893 928 10.1021/cr00005a013
Bader, R. F. W. A quantum theory of molecular structure and its applications. Chem. Rev. 91(5), 893–928 (1991).
70. Adalikwu SA Louis H Iloanya AC Edet HO Akem MU Eno EA Manicum ALE B-and Al-doped porous 2D covalent organic frameworks as nanocarriers for biguanides and metformin drugs ACS Appl. Bio Mater. 2022 5 12 5887 5900 10.1021/acsabm.2c00855 36413624
Adalikwu, S. A. et al. B-and Al-doped porous 2D covalent organic frameworks as nanocarriers for biguanides and metformin drugs. ACS Appl. Bio Mater. 5(12), 5887–5900 (2022).36413624
71. Adalikwu SA Edet HO Gber TE Adeyinka AS Louis H Boron and oxygen decorated Zn-doped aluminum/boron nitride and graphene/boron nitride heterostructures for the adsorption of phosgene gas: Density functional theory outlook Comput. Theor. Chem. 2024 1233 114495 10.1016/j.comptc.2024.114495
Adalikwu, S. A., Edet, H. O., Gber, T. E., Adeyinka, A. S. & Louis, H. Boron and oxygen decorated Zn-doped aluminum/boron nitride and graphene/boron nitride heterostructures for the adsorption of phosgene gas: Density functional theory outlook. Comput. Theor. Chem. 1233, 114495 (2024).
72. Ezzat HA Hegazy MA Nada NA Osman O Ibrahim MA Development of natural polymer/metal oxide nanocomposite reinforced with graphene oxide for optoelectronic applications NRIAG-JAG 2021 10 1 10 22
Ezzat, H. A., Hegazy, M. A., Nada, N. A., Osman, O. & Ibrahim, M. A. Development of natural polymer/metal oxide nanocomposite reinforced with graphene oxide for optoelectronic applications. NRIAG-JAG 10(1), 10–22 (2021).
