Cemal Parlak , Özgür Alver and Ponnadurai Ramasami

Interaction mechanisms and structural properties of B-, Si-doped C60 fullerenes with 1-formylpiperazine

De Gruyter | Published online: October 21, 2016


Piperazines and fullerene nanocages are versatile compounds. These are discussed in a wide range of academic work, especially in the field of medicine, and considered for various applications by the pharmaceutical industry. In the present research, the potential interaction mechanisms between B-, Si-doped C60 and 1-formylpiperazine (1-fp) were examined within the framework of density functional theory, along with their optimized molecular structures and electronic properties. The calculated binding energies and various other physical and chemical parameters of 1-fp found in this work in comparison with the Si- and B-doped fullerenes suggest that doping of fullerene nanocage leads to a strong interaction mechanism that alters the chemical and electronic properties of the investigated compounds. This finding can be used as a guide for their further applications.


Piperazine and its derivatives have found a vast majority of applications in many fields of science, such as chemistry, and in the pharmaceutical industry (Beyeh et al., 2010; Davies et al., 2010; Long et al., 2010; Hatnapure et al., 2012; Li et al., 2014a). For example, several piperazine derivatives have been used as ligands in the synthesis of different types of complexes and clathrates (Parlak et al., 2009a,b). N-substituted piperazine compounds have been shown to have a very wide range of pharmaceutical properties that range from anticancer, antifungal, and antimicrobial to tuberculoastic activities (Liang et al., 2004; Foks et al., 2005; Jiang and Huang, 2012; Wu et al., 2014; Menezes et al., 2016). Further, 1-fp is often in the center of scientific studies, such as those devoted to the synthesis of some antihypertensives, male antifertility products, receptor antagonists, as well as studies investigating the compounds of dopamine D4 receptor imaging (Dwivedi et al., 1991; Ferrarini et al., 1998; Oh et al., 2004; Takahashi et al., 2006).

Density functional theory (DFT) is widely used for the pre-evaluation of synthesized or designed molecular systems due to its low cost and practical applications (Helgaker et al., 1999; Dheivamalar and Sugi, 2015; Hassani and Tavakol, 2014; Li et al., 2015). DFT method has the advantage of giving some insights before experimental applications to avoid excessive amounts of useless experimental efforts. Since their appearance in 1985, fullerenes have enjoyed great attention as suitable candidates for drug delivery systems (Kroto et al., 1985; Bakry et al., 2007; Singh and Lillard, 2009). They have also been in the search for organic photovoltaic devices because of their excellent electronic properties (Renz et al., 2008). In the current research, DFT is used to determine the possible interaction edges of Si-, B-doped C60 fullerenes with 1-fp molecule, thus enabling us to evaluate the fullerene cage as a possible candidate to carry this potentially important molecule for further applications.

Computational details

In order to find the stable configurations of the investigated systems, structures are typically built and geometry optimizations are completed without applying any geometrical restrictions. For large molecular systems, we often encounter imaginary frequencies at the end of the frequency calculations of the optimized structures. This is an indication of a transition structure and not a global energy minimum on the potential energy surfaces. Therefore, in such cases, the optimization process is repeated until no imaginary frequencies are observed at the end of vibrational frequency calculations of the examined structures. In the current study, calculations were carried out using M062X and B3LYP functionals with the 6-31G(d) basis set in both gas and water solvent media. To perform stability and structural assessments and to understand the adsorption mechanisms, binding energy (Eb), frontier energy gap (Eg), chemical hardness (η), and electrophilicity index (ω) were also calculated. Calculations were performed with Gaussian 09 (Frisch et al., 2009). A pictogram of the optimized molecular systems was created using GaussSum and GaussView programs (O’Boyle et al., 2008; Dennington et al., 2009).

Results and discussion

The conformational and vibrational properties of 1-fp have been reported in a previous study (Keşan and Parlak, 2014). On the basis of previously reported data (Keşan and Parlak, 2014) and on calculated electrostatic potential surface (EPS) (Figure 1), two interaction points, O and NH found more negative on the EPS of 1-fp, were suggested as interaction edges with the doped fullerene systems. As can be clearly seen in Figure 1, the introduction of water as a solvent and optimization media slightly changed the charge distribution, particularly at the interaction edges (O, NH). Clearly, hydrogen bonding has a very important impact on the stability and Eb energies of molecular systems (Li et al., 2014b; Djikaev and Ruckenstein, 2016; Ragavendran and Muthunatesan, 2016). Therefore, water inevitably interacts with ligand and doped fullerene cages, thus leading to changes on the adsorption properties and strength of the binding energies.

Figure 1: Electrostatic potentials on 1-fp.Surfaces are defined by the 0.0004 electrons/b3 contour of the electronic density. Color ranges, in a.u.: blue: more positive than 0.032 and red: more negative than –0.032.

Figure 1:

Electrostatic potentials on 1-fp.

Surfaces are defined by the 0.0004 electrons/b3 contour of the electronic density. Color ranges, in a.u.: blue: more positive than 0.032 and red: more negative than –0.032.

Considering these interaction sites, optimized structures were obtained, as shown in Figure 2. Boron and silicon atoms were chosen as the active sites for B- and Si-doped fullerene cages, as reported by Hazrati and Hadipour (2016). Effective physical adsorption or interaction of different types of host and guest molecular systems not only relate to the polarity of interaction sites but also to many other factors, such as molecular dynamics, molecular structure, and optimization conditions (Zolek et al., 2003; Umadevi and Sastry, 2012; Izadyar and Housaindokht, 2016). By checking the only partial charges, it is difficult to know which site is more suitable for interaction. However, based on the conclusions of Eb energies, it can be concluded that the BC59…NH system in the gas phase and in water media is more favorable than the BC59…O system, which is confirmed by the calculations of both the M062X and B3LYP functionals. This fact suggests that BC59 and NH of ligand molecule seem to interact more efficiently or boron of C59 can more easily reach and interact with NH than BC59 and O, considering the previously mentioned factors.

Figure 2: Optimized molecular structures for the investigated systems by M062X/6-31G(d) in the gas phase.

Figure 2:

Optimized molecular structures for the investigated systems by M062X/6-31G(d) in the gas phase.

The binding and solvent energies (Eb, Esolv) calculated by B3LYP/6-31G(d) and M062X/6-31G(d) methods in both the gas phase and water environment are given in Table 1. Silicon and boron have different chemical properties. For example, doping with silicon does not cause a change in the net occupancy of the energy level compared with boron, because silicon and carbon include the same number of valance electrons (Hazrati and Hadipour, 2016). Furthermore, functionals used in the search for Eb energies have potential effects (Bryantsev et al., 2009) that can lead to some differences in the Eb energies. Considering these Eb energies both in the gas and water phases, the interaction with BC59 with NH edge of 1-fp seems to lead to a more stable configuration than the BC59…O structural system. However, these Eb energies of SiC59…NH and SiC59…O structures are almost the same for both gas and water environments. Compared with the gas phase, all the investigated systems in the water phase have lower or more negative Eb energy (Table 1). Based on the Esolv energy, it can be concluded that the solubilities of the BC59…NH and SiC59…NH systems have a higher degree than those of the BC59…O and SiC59…O systems, because they have more negative Esolv energies (Table 1). The generally accepted energy range for a chemisorption to occur is known to be 10–100 kcal/mol (Bhushan, 1999). This suggests that, considering the Eb values obtained in this work for the investigated systems, a chemisorption occurs between 1-fp and B-, Si-doped fullerene systems.

Table 1:

Binding and solvent energies (kcal/mol) of the investigated systems.

Structure M062X/6-31G(d) B3LYP/6-31G(d)
Eb (gas) Eb (water) ESolv Eb (gas) Eb (water) ESolv
BC59…NH –40.74 –45.74 –12.39 –27.17 –31.95 –12.05
BC59…O –22.94 –26,51 –10.95 –21.17 –24.51 –10.62
SiC59…NH –41.25 –51.55 –18.01 –26.41 –37.13 –18.03
SiC59…O –41.79 –51.04 –16.97 –29.89 –39.02 –16.43

As can be followed quantitatively on the density of state (DOS) graphs for B- and Si-doped fullerenes (Figure 3), changing the optimization media from gas to water and interaction sites from NH to O causes some changes in the Eg energies. However, this change is almost negligible from SiC59…NH (gas) to SiC59…O (gas) with an amount of 0.001 eV.

Figure 3: DOS spectra of the investigated structures by M062X/6-31G(d).

Figure 3:

DOS spectra of the investigated structures by M062X/6-31G(d).

The calculated data for electrophilicity (ω) for the investigated systems show an increase for the structures calculated with the M062X and B3LYP functionals (Table 2). This means that the electrophilic characters of the structures BC59…O and SiC59…O are lower than the BC59…NH and SiC59…NH systems for both gas and water media. Meanwhile, chemical hardness is a measure of resistance to the charge transfer (Makov, 1995), which is strictly related to the doped atom and solvent media. Thus, this may vary depending on the different dopants used for the studied complexes. Chemical hardness of the SiC59…NH and SiC59…O complexes showed very similar results for M062X and B3LYP functionals in the gas phase and water media calculations (Table 2). Furthermore, chemical hardness of the BC59…NH system is higher than that of the BC59…O system with M062X/6-31G(d) level. However, the opposite of this can be observed with the results calculated at B3LYP/6-31G(d) level. This finding suggests that, unlike the electrophilicity indexes, chemical hardness shows different characteristics based on the employed theoretical level. Moreover, B…NH, B…O, Si…NH and Si…O distances have been reduced owing to changes from gas to water media; hence, the binding energy becomes more negative as expected (Table 3).

Table 2:

Some energetic parameters (eV) of the investigated structures.

Structure HOMO LUMO Gap Chemical hardness Electrophilicity index
  BC59…O –5.714 –2.074 3.640 1.820 4.166
  BC59…NH –5.995 –2.307 3.688 1.844 4.672
  SiC59…O –5.597 –1.865 3.732 1.866 3.730
  SiC59…NH –5.885 –2.154 3.731 1.866 4.330
  BC59…O –5.937 –2.363 3.574 1.787 4.819
  BC59…NH –5.979 –2.394 3.585 1.793 4.889
  SiC59…O –5.858 –2.279 3.579 1.790 4.625
  SiC59…NH –5.924 –2.327 3.597 1.790 4.732
  BC59…O –4.671 –2.562 2.109 1.055 6.202
  BC59…NH –4.921 –2.833 2.088 1.044 7.199
  SiC59…O –4.493 –2.391 2.102 1.051 5.636
  SiC59…NH –4.775 –2.672 2.103 1.052 6.593
  BC59…O –4.890 –2.866 2.024 1.012 7.430
  BC59…NH –4.894 –2.896 1.998 0.999 7.593
  SiC59…O –4.749 –2.779 1.970 0.985 7.192
  SiC59…NH –4.801 –2.821 1.980 0.990 7.335
Table 3:

Some optimized distances (Å).

Length M062X B3LYP M062X B3LYP
Gas Water
B…NH 1.63 1.66 1.62 1.64
B…O 1.60 1.60 1.56 1.56
Si…NH 1.92 1.95 1.88 1.92
Si…O 1.80 1.83 1.75 1.76

Table 4 shows the variations of NH and C=O stretching vibrations before and after the interaction. As can be clearly seen, the interaction of 1-fp with Si-, B-doped cages causes some severe alterations with the vibrational frequencies of interaction edges of NH and C=O as expected. In Table 4, the effects of solvent, dopant atom, and the methods used for calculations on the vibrational frequencies of NH and C=O bands can be clearly observed.

Table 4:

NH and C=O stretching frequencies for the studied complexes.

Structure NH stretching C=O stretching
Gas Water Gas Water
 1-fp 3506 3506 1797 1750
 BC59…O 3522 3515 1715 1708
 SiC59…O 3526 3520 1709 1719
 BC59…NH 3413 3422 1805 1757
 SiC59…NH 3398 3407 1808 1760
 1-fp 3551 3546 1850 1797
 BC59…O 3557 3547 1750 1733
 SiC59…O 3561 3570 1745 1773
 BC59…NH 3428 3446 1858 1799
 SiC59…NH 3419 3414 1861 1808


The interaction mechanism of B-, Si-doped C60 fullerenes and 1-fp molecule were investigated based on the quantum mechanical calculations, which used M062X and B3LYP functional with 6-31G(d) basis, set in both gas and water environments. For the most stable configurations, two interaction sites were included with 1-fp labelled with NH and O. The stabilities of the investigated systems showed dependence on the computational methods and the solvent media. For instance, it was observed that structures became more stable in water compared with those in the gas phase. The most stable structure obtained with M062X method was the SiC59…NH structure with a binding energy of –51.55 kcal/mol, which is slightly smaller (more negative) than SiC59…O system with a binding energy of –51.04 kcal/mol. In comparison, the most stable structure suggested by the results of B3LYP method was found to be SiC59…O, with a binding energy of –39.02 kcal/mol.


We acknowledge the computing resources provided by Fencluster system in the Science Faculty of Ege University. The authors are also thankful to the anonymous reviewers, whose comments proved useful in revising the manuscript.


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Received: 2016-7-5
Accepted: 2016-9-15
Published Online: 2016-10-21
Published in Print: 2016-12-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

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