HOMO-LUMO photosensitization analyses of coronene-cytosine complexes

1 Introduction

Cancer has been almost the main serious problem for human health system for several years without any certain treatment for patients yet [1]. Some types of invasive and non-invasive methods have been developed for treatments of cancer to this time; however, the problem has been growing faster than the treatment methodologies and protocols [2]. Therefore, it still is an important issue to focus on developing new methods or protocols for treatments of cancer patients [3]. To this aim, photodynamic therapy (PDT) has been seen among the most versatile techniques for treatments of various types of cancers such as skin cancer [4]. Photosensitization works as the major part of PDT mechanism by help of an external light resource radiation and a photosensitizer (PS) compound to absorb the radiated light to convert to energy for reactive oxygen production blocking the cancer cells growth [5]. In this case, PS compound is almost the central working motor of PDT for light absorption and energy conversion [6]. For better description, it could be mentioned that a PS compound could work as a photosensor by adsorption of light with specified wavelengths [7]. As shown in Fig. 1, the energy transition from the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO) is a crucial step of photosensitization happening by absorption of light radiation [8]. In this case, the absorbed energy could somehow work as a new energy resource for providing radiation to the targeted cells [9]. In other words, the absorbed energy could be released to provide required energy for reactive oxygen production in the reversed mode [10]. Hence, it is worth to mention that the compounds with capability of contributing to such energy absorbing and releasing could work as useful PS compounds for employing in PDT processes [11–13]. The wavelength of light radiation is conventionally in the range of ultraviolet (UV) even visible; therefore, designing PS compounds with capability of energy absorbing in the mentioned wavelength region is important [14]. To approach this goal, employing nanostructures for PS compounds could be an advantage because of their unique roles in various electronic related devices and applications [15]. However, the nanostructure itself is not originally biocompatible and its modification is required for preparation for employing n biological media [16]. Biological molecules such as nucleobases have been seen already as useful modifiers for nanostructures to improve their biocompatibility [17]. By such modification, the HOMO-LUMO photosensitization mechanism could be examined for innovating new PS compound for PDT applications [18]. To do such small-scale investigation, performing quantum chemical (QC) calculations could help to achieve the purpose [19–21]. Indeed, the high-level QC methods could very well recognize electronic and structural features of compounds at the lowest scales of molecular, atomic, even subatomic units [22]. In this work, such advantage of QC calculations was employed to analyze HOMO-LUMO photosensitization mechanism for models of coronene-cytosine complexes (Fig. 2) for making sense the idea of new PS compounds innovation.

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Fig. 1

HOMO-LUMO energy transition.

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Fig. 2

(–HC = CH–)_n assisted Cor-n-Cyt complex models; n = 0, 1, 2, and 3.

Cytosine (Cyt) is a pyrimidine nucleobase found in both of DNA and RNA, in which its carbon-5 position has been seen possible to be functionalized by other atomic and molecular substances [23]. Coronene (Cor) is a single molecular unit of graphene carbon monolayer, in which such atomic and molecular functionalization has been seen possible for this structure [24]. Singular models of Cyt and Cor were exhibited in Fig. 3. Unique electronic features of carbon monolayers in addition to importance of biological molecular functionalization of them has leaded to idea of Cor-Cyt complex formation for photosensitization application [25, 26]. To construct such complex systems, ethylene (–HC = CH–) was used as the linker between Cor and Cyt with n times of repeating unit indicated by Cor-n-Cyt; n = 0, 1, 2, and 3 (Figs. 2 4). The models were stabilized employing QC calculations and the HOMO-LUMO photosensitization descriptors were evaluated for the stabilized complexes. Hence, the required information were summarized in Tables 1 2 and Figs. 2 4 to achieve the goal of this work.

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Fig. 3

Parent cytosine (Cyt) and coronene (Cor) models with HOMO/LUMO distribution patterns.

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Fig. 4

Cor-n-Cyt complex models; n = 0, 1, 2, and 3, with HOMO/LUMO distribution patterns.

Cytosine (Cyt) and coronene (Cor) were two singular models for making Cor-n-Cyt complexes by means of (–HC = CH–)_n linker by varying n = 0, 1, 2, and 3 (Fig. 2). As a result, four models of complexes were provided for this work as representative models for such hybrid complex system undergoing HOMO-LUMO photosensitization analyses (Fig. 4). Geometries of singular and complex models were optimized at the B3LYP/6-31 + G^* level of density functional theory (DFT) as implemented in the Gaussian program [27]. All optimized geometries were confirmed by performing additional frequency calculations avoiding the existence of any imaginary frequency for the stabilized structures. By doing these calculations, the models were supplied for performing further analyses by means of evaluated chemical descriptors and photosensitization features. Values of binding energy (BE), dipole moment (DM), ionization potential (IP), electron affinity (EA), chemical hardness (H), and chemical softness (S) were evaluated for the optimized models as chemical descriptors summarized in Table 1. For performing HOMO-LUMO photosensitization analyses, values of HOMO, LUMO, energy gap (EG), and energy absorption wavelength (λ), were summarized in Table 2. Furthermore, distribution patterns of HOMO and LUMO of all models were exhibited in Figs. 3 4 in addition to representation of the optimized models. This work was done by the advantage of performing QC calculations to investigate features at molecular, atomic, and subatomic scales of models of this work to provide insightful information for examining idea of new PS compounds innovation [28, 29]. For more clarification of the employed procedure for achieving the goal of this work, it could be mentioned that molecular and atomic scales calculations could yield insightful information for the investigated materials by analyzing the features at the smallest scales. Therefore, in continuous procedures of molecular designing, optimizing, and analyzing, the required descriptors for analyzing the materials could be achieved [30–33].

3 Results and discussion

The main goal of this work was to perform HOMO-LUMO photosensitization analyses for examining the idea of new PS compounds innovation (Fig. 1). To this aim, models of Cor and Cyt were considered for constructing Cor-n-Cyt complexes by means of (–HC = CH–)_n linkers; n varying by 0, 1, 2, and 3 (Fig. 2). DFT calculation were performed to stabilize each of singular and complex systems as shown in Figs. 3 4 to evaluate chemical and photosensitization related descriptors as listed in Tables 1 2. Based on linker-assisted combinations of Cor and Cyt, four models of Cor-n-Cyt were obtained through performing optimization processes. In Cor-0-Cyt model, the Cyt counterpart was directly connected to the Cor counterpart without linker whereas 1, 2, and 3 linker groups helped to construct each of Cor-1-Cyt, Cor-2-Cyt, and Cor-3-Cyt complexes, respectively. The optimized models of singular and complex forms were exhibited in Figs. 3 4, in which all models were planar instead of Cor-0-Cyt model. The size of model was important, therefore numbers of linkers were limited up to three (–HC = CH–) groups. Comparing the obtained values of BE could show that favorability of complex formation was more suitable for direct connection of Cyt to Cor in Cor-0-Cyt complex and such favorability was reduced by increasing the n number. The variation of values of DM was interesting, in which the zero-value of Cor was significantly increased by Cyt functionalization remembering the importance of such biological functionalization for reducing toxicity of nanostructures. Moreover, the values of DM for Cor-n-Cyt models were also larger than that of singular Cyt model showing the impact of functionalization on electric charge distributions and orientations of structures. The obtained IP and EA values could show the tendency of electron transferring of a substance versus other substances in donating or accepting modes, respectively. In the investigated models, the values of IP could mean that the complex models were generally more suitable for electron donating than EA assigned electron accepting. As a result, these complex models could be supposed for contribution to reactions as a source of electron for donating process. To see this point clearly, the obtained values of H and S could show that the hardness of complexes was decreased whereas the softness was increased revealing better possibility for participating in interactions or reactions in comparison with the singular models. It should be noted here that the features of complex models were also different in comparison with each other meaning the impact of functionalized models for innovating specific compounds. As a consequence, the models were stabilized and variations of chemical descriptors were observed for the models leading to analyzing HOMO-LUMO photosensitization features.

HOMO-LUMO photosensitization descriptors were evaluated for the optimized models and they were summarized in Table 2 and representing features were shown in Figs. 3 4. As mentioned earlier, such energy absorption and conversion could determine advantage of application of a substance as a PS compound for investigating further features for PDT purposes. In this regard, values of HOMO, LUMO, EG, and λ were obtained for the optimized models to show their capability for participating in the photosensitization process. The highest occupied level and the lowest unoccupied level are both very much important for making possible energy transition with two levels. Based on electronic and structural configurations of compounds, the procedure of such energy transition could be changed to show different features of specified purposes. The gap between these two levels assigned by HOMO and LUMO could show indeed the distance for reaching the energy transition, in which longer or shorter distances could yield different features for the compounds. Moreover, such energy distance could be proportional to the wavelength in a reversed mode. Therefore, longer distances of energy could be proportional to shorter wavelengths might be harmful for human health. To run such PDT process, the values of λ∼200–400 nm could be defined in UV region for absorption process. The obtained results of investigated models indicated that the energy distance was reduced in the complex models in comparison with the singular models. Among the complex models, Cor-3-Cyt was at the shortest distance for HOMO-LUMO levels whereas Cor-0-Cyt was at the longest distance. Examining the values of HOMO and LUMO could show that both energy levels were changed in the complex models, in which the route of variation was to lowering the energy distance as assigned by EG. Accordingly, the values of λ for energy absorption process were changed regarding the values of required energy. Such subatomic energy transition could be mentioned in another way to show the conversion of PS to PS^* for initiating the therapy process. The reactive mode of PS assigned by PS^* could be obtained by such energy absorption process from an external light radiating resource, in which such PS^* compound could relax to PS compound again by energy luminescence to reach the ground state. In the subatomic point, HOMO-LUMO transitions in ↑↓ modes could mean such PS to PS^* or PS^* to PS energy conversions by energy absorption from an external resource or energy luminescence to media. In PDT, such energy luminescence could work for generating reactive oxygen substances to block the cancer growth mechanism. Indeed, PS^* could work as a secondary resource of energy in human body for initiating the therapy process inside the body. To this aim, careful analyses of HOMO-LUMO transitions could help to achieve the purpose of this work to show the favorability of a compound for energy absorption to provide a possible secondary resource of energy. Comparing the results of investigated models could show that the models were moved into shorter energy distances with higher absorption wavelengths, in which the models were moved from high energy UV to low energy UV even visible region. The order of λ of complexes was Cor-0-Cyt < Cor-1-Cyt < Cor-2-Cyt < Cor-3-Cyt meaning that the linker helped to move the complex models from higher to lower required absorption energy strength as an advantage of new PS compounds. Indeed, such process could help PS compounds to work inside the body for receiving energy resource radiation in a safe mode. Each of singular Cor and Cyt required higher levels of absorption energy, in which such levels were reduced in the complex models. In addition to the size of model, reaching to visible region for energy absorption was another limitation for using numbers of linkers up to 3. In addition to quantitative values, qualitative representations of Figs. 3 4 could also show the impact of functionalized models on HOMO and LUMO distribution patters of molecular counterparts by assistance of (–HC = CH–) linker. Indeed, such linker kept the aromaticity environment for the complex models and the evaluated distribution patterns showed advantage of using such linker for complex formations of this work. As a consequence, HOMO-LUMO analyses indicated that the models were found to be suitable for photosensitization process according to Cor-n-Cyt complex formations with more or less significant impacts of such process making them applicable for specific applications of PDT purposes.

4 Conclusion

HOMO-LUMO photosensitization analyses of models of (–HC = CH–)_n assisted Cor-n-Cyt complexes; n varying by 0, 1, 2, and 3, were investigated in this work for making sense and idea of new PS innovation for PDT applications. By the importance of absorption energy of PS compounds to move to PS^*, electronic and structural features of the models were investigated through performing DFT calculations. The models were stabilized and their evaluated chemical descriptors indicated that the models detected variations of features from singular to complex models even among the complex models. Chemical reactivity features indicated that the complex models could work easier in reaction processes in with more favorability of electron donating with lower hardness and higher softness modes. The evaluated photosensitization descriptors indicated that the modes were suitable for absorbing energy with longer wavelengths meaning that safety of models were increased regarding the impact of radiating on human health level. As a result, the investigated Cor-n-Cyt complex systems of this work could be proposed for PS applications of PDT purposes, in which they showed advantage of lower energy requirements from external radiating resources.