Single or functionalized fullerenes interacting with heme groupWallison Chaves Costa and Eduardo Moraes Diniz Citation: AIP Advances 4, 097119 (2014); doi: 10.1063/1.4895804 View online: http://dx.doi.org/10.1063/1.4895804 View Table of Contents: http://scitation.aip.org/content/aip/journal/adva/4/9?ver=pdfcov Published by the AIP Publishing Articles you may be interested in Photoluminescence spectroscopy of YVO4:Eu3+ nanoparticles with aromatic linker molecules: A precursor tobiomedical functionalization J. Appl. Phys. 115, 163107 (2014); 10.1063/1.4874179 Spin transport properties of single metallocene molecules attached to single-walled carbon nanotubes via nickeladatoms J. Chem. Phys. 134, 244704 (2011); 10.1063/1.3603446 Impact of ligands on CO 2 adsorption in metal-organic frameworks: First principles study of the interaction of CO2 with functionalized benzenes. II. Effect of polar and acidic substituents J. Chem. Phys. 132, 044705 (2010); 10.1063/1.3276105 Electronic effect of kink in the edge dislocation in bcc iron: A first-principles study J. Appl. Phys. 100, 023715 (2006); 10.1063/1.2217984 Electronic structure and bonding in unligated and ligated Fe II porphyrins J. Chem. Phys. 116, 3635 (2002); 10.1063/1.1447902

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AIP ADVANCES 4, 097119 (2014)

Single or functionalized fullerenes interactingwith heme group

Wallison Chaves Costa and Eduardo Moraes Diniza

Departamento de Fısica, Universidade Federal do Maranhao, Avenida dos Portugueses,1966, CEP 65080-805, Sao Luıs - MA, Brazil

(Received 18 June 2014; accepted 3 September 2014; published online 12 September 2014)

The heme group is responsible for iron transportation through the bloodstream,where iron participates in redox reactions, electron transfer, gases detection etc.The efficiency of such processes can be reduced if the whole heme molecule oreven the iron is somehow altered from its original oxidation state, which can becaused by interactions with nanoparticles as fullerenes. To verify how such particlesalter the geometry and electronic structure of heme molecule, here we report firstprinciples calculations based on density functional theory of heme group interactingwith single C60 fullerene or with C60 functionalized with small functional groups(−CH3, −COOH, −NH2, −OH). The calculations shown that the system heme +nanoparticle has a different spin state in comparison with heme group if the fullereneis functionalized. Also a functional group can provide a stronger binding betweennanoparticle and heme molecule or inhibit the chemical bonding in comparison withsingle fullerene results. In addition heme molecule loses electrons to the nanoparticlesand some systems exhibited a geometry distortion in heme group, depending on thebinding energy. Furthermore, one find that such nanoparticles induce a formation ofspin up states in heme group. Moreover, there exist modifications in density of statesnear the Fermi energy. Although of such changes in heme electronic structure andgeometry, the iron atom remains in the heme group with the same oxidation state,so that processes that involve the iron might not be affected, only those that dependon the whole heme molecule. C© 2014 Author(s). All article content, except whereotherwise noted, is licensed under a Creative Commons Attribution 3.0 UnportedLicense. [http://dx.doi.org/10.1063/1.4895804]

I. INTRODUCTION

Nanomaterials are present in many areas of modern life, as food products, industry, electronicsand pharmacy. As a consequence, the exposure to such materials is not limited to people involvedin their preparation, but actually to the ordinary population, as for example nanomaterials that havebeen used in cosmetics1, 2 or drug delivery3–5 in the last few years. Despite the increasing use ofthose materials, little attention has been devoted to their bad influence in human body,6, 7 as toxicityor the chemical changes that such structures can induce in biomolecules, as the heme group, presentin hemoglobin and very important to many biological processes.

The heme iron, located in the center of a porphyrin, plays an important role in oxygen trans-portation, redox reaction, among others, where in the former the gas molecule binds to the heme ironand in the latter the heme iron serves as electron source or drain. The efficiency of these biologicalmechanisms could be reduced if there are changes in the iron electronic state, which can be causedby interactions with nanoparticles, as nanotubes or fullerenes.8

To date, there is no first principles calculations concerning on the interactions between hememolecule and fullerenes, only semiempirical methods have been employed.8, 9 In order to investigate

aElectronic mail: eduardo.diniz@ufma.br

2158-3226/2014/4(9)/097119/7 C© Author(s) 20144, 097119-1

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097119-2 Wallison Chaves Costa and Eduardo Moraes Diniz AIP Advances 4, 097119 (2014)

the influence of nanoparticles in heme iron, more specifically charge transfers, changes in HOMO,LUMO and density of spin, here we report first principles calculations of the heme B interactingwith C60 fullerene in its single form or functionalized with −CH3, −COOH, −NH2 and −OH. In thenext section we explain the methods applied to this study, followed by the main results concerningthese calculations. The last section is devoted to the conclusions.

II. METHODS

To perform this study, we applied first principles calculations based on density functionaltheory10, 11 using generalized gradient approximation (GGA) with the PBE12 parametrization forthe exchange-correlation potential, as implemented by the SIESTA13 code. Optimization wasachieved when the maximum atomic force remained lower than 0.01 eV/Å. Troullier-Martins14

norm-conserving pseudopotentials were used in the Kleimann-Bylander15 form. All spin-polarizedcalculations were performed with a standard double-ζ plus polarization orbitals basis set with areal-space grid determined by an energy cutoff of 400.0 Ry. In order to evaluate the correct order forbinding energy calculations, basis set superposition error was considered through the ghost orbitalsmethod.13

III. RESULTS

All nanoparticles were initially placed near heme iron. As our intention is figuring out howdifferent functionalized fullerenes could change the heme molecule properties, and taking in accountthat small functionalizations alter locally the fullerene electronic structure or their influences aremore significant near the functionalization itself, the functional group was situated close to the Feand a fully geometry optimization was performed as explained in the previous section. None ofthe nanoparticles was capable of removing the iron from porphyrin. Figure 1 shows all optimizedgeometries, where heme molecule alone is shown in Figure 1(a) exhibiting a planar porphyrinsurrounded by out-of-plane terminations. One can see major distortions of the heme molecule whenit interacts with C60COOH, C60NH2 and C60OH, shown in this order in Figures 1(d), 1(e) and 1(f).Small distortions of heme molecule are verified in Figures 1(b) and 1(c), where heme interactswith C60 and C60CH3, respectively. The shortest atom-atom distance between the non-biologicalmolecule and the heme iron ranges from 2.1 Å to 2.8 Å for heme + C60COOH (closest) and heme+ C60CH3 (farthest), shown in Figures 1(d) and 1(c), respectively.

The calculations lead to quintet spin state for heme group as the lowest energy state in comparisonwith singlet or triplet (second lower) ones. For heme interacting with nanoparticles, the lowest energyspin state remains as quintet when heme interacts with C60, but it changes to septet when the fullereneis functionalized. Such findings for lowest energy states are due to the nanoparticle total spin, whichis singlet for C60 and triplet for functionalized fullerenes. The second lower energy spin state issinglet for heme + C60 while for functionalized fullerenes interacting with heme group, one hastriplet for heme + C60CH3 and quintet for the remaining systems.

After the structural optimization, additional calculations using ghost orbitals were performed toevaluate the binding energy defined as

Eb = Enp + heme − (Enp + Eheme)

where np means nanoparticle. Table I shows the binding energies and as one can see, only C60CH3has a positive binding energy, which explains why the functionalized fullerene remained away fromheme group in this system. For all other cases the binding energy is negative, indicating that isenergetically more favorable to the system remain bonded. In addition, the functional group plays animportant role in the binding energy, since the values of Eb are more negative when functionalizationis present, mainly for C60COOH, where its binding energy is almost thirty times the correspondentvalue for heme + C60 (see Table I). This explains why C60COOH has the shortest distance to theheme group. Therefore, for biological applications, we infer that −CH3 functional group couldprovide a less harmful nanoparticle with respect to changes in the electronic properties of hemegroup and C60COOH would be a good candidate to deliver specific molecules directly to the heme

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097119-3 Wallison Chaves Costa and Eduardo Moraes Diniz AIP Advances 4, 097119 (2014)

FIG. 1. Optimized geometries. C, H, O, N and Fe atoms are labeled by yellow, blue, dark red, gray and light red spheres,respectively.

TABLE I. Binding energy (Eb) and difference in total number of electrons in heme group (�q), variations of heme ironvalence (�qFe) and magnetic moment (�μFe) in comparison with respective values for heme group alone. Energy, chargetransfers and magnetic moment are given in eV, e and μB, respectively.

Structure Eb �q �qFe �μFe

Heme + C60 − 0.015604 − 0.156 0.151 − 0.211Heme + C60CH3 0.075963 − 0.199 − 0.046 0.044Heme + C60COOH − 0.449375 − 0.212 0.017 0.237Heme + C60NH2 − 0.155323 − 0.205 0.014 0.192Heme + C60OH − 0.184038 − 0.284 − 0.006 0.220

group due to its lower binding energy. Also one can relate geometry distortions on heme moleculecaused by a nanoparticle with the binding energy, since Table I shows that systems with a smallvalue for Eb exhibited great distortions on heme molecule.

By analyzing the Mulliken population,16 we found charge transfers from heme group to nanopar-ticles, where the values are nearly the same for all systems. Table I shows the difference �q of thenumber of electrons of the heme group interacting with C60 (single or functionalized) in comparisonwith heme group alone. In this same Table one has the values of changes in heme iron total charge(�qFe) and magnetic moment (�μFe), again compared with data from heme group alone. As onecan see, for most systems, the heme iron does not change its oxidation state, once there is no mod-ification in valence charge. The only alteration in Fe electron number is for heme + C60, but thisrepresents less than 2% of increasing in charge valence in comparison with heme iron. So, for those

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097119-4 Wallison Chaves Costa and Eduardo Moraes Diniz AIP Advances 4, 097119 (2014)

FIG. 2. Spin density surfaces. All surfaces have an isovalue of 0.001 e/bohr3. Spin up (down) surfaces are red (blue).

nanoparticles, heme iron does not serve as electron source or drain but the others atoms in hemegroup contribute to this charge loss.

Magnetic states present in heme group are concentrated around Fe atom, as expected. Whenthe nanoparticles interact with the heme molecule, they induce modifications in spin up/downdistributions, which modifies the iron magnetic moment, as shown in Table I. Such variationsdisseminate in heme molecule, creating magnetic states that did not exist before the interaction withthe nanoparticle. Figure 2 shows the spin density surface for an isovalue of 0.001 e/bohr3 for hemegroup alone, shown in Figure 2(a) and interacting with the nanoparticles.

All nanoparticles induced the creation of spin up states in heme molecule. The variation in μFe

is associated with magnetic states created between Fe and the nanoparticle. For heme + C60CH3,the large distance between iron and the functional group shown in Figure 2(c) prevented significantmodifications in iron spin state, as shown in Table I. The only reduction of μFe in Table I happensfor heme + C60 due to the creation of spin down states near heme iron, as shown in Figure 2(b).The remaining systems exhibited an increasing in iron magnetic moment, which can be explainedby the presence of spin up states between the iron and the nanoparticle, as shown in Figures 2(d),2(e) and 2(f) with more emphasis in C60COOH, the closest nanoparticle, which induced the greatestvariation in μFe.

For comparison, such findings for heme interacting with nanoparticles in the second lowerenergy spin state of each system are very similar for charge transfers (not shown here) in comparisonwith the lowest energy spin states results but are very different for Fe magnetic moment, as expected,since the total spin state is due mainly to the Fe. For heme + C60, the change �μFe is again negative(−1.27 μB), while functionalized fullerenes induced a change in Fe magnetic moment of 0.88 μB

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097119-5 Wallison Chaves Costa and Eduardo Moraes Diniz AIP Advances 4, 097119 (2014)

FIG. 3. HOMO/LUMO wave functions for heme group alone or interacting with nanoparticles. Different surface colorsmean opposite wavefunction signals.

in average. Therefore, changes in Fe magnetic moment for the second lower energy spin state aremore than three times greater than equivalent values for the lowest energy spin state.

Due to charge transfers and changes in iron magnetic moment, which involve the most energeticelectrons, there exist great modifications in HOMO and LUMO shapes of heme molecule, as shownin Figure 3. Heme exhibits HOMO with bonding π and dxz orbitals in C-C bonds and Fe, respectively.Heme LUMO also exhibits π orbitals in C-C bonds and a dyz orbital in Fe, as shown in Figures 3(a)and 3(b).

All functionalized fullerenes caused a change in d orbital character of HOMO in comparisonwith heme alone. C60COOH and C60NH2, shown in Figures 3(g) and 3(i), respectively, induced amodification to a dyz format, while C60CH3 and C60OH, shown in Figures 3(e) and 3(k), respectively,to a dxy shape. The d orbital character of HOMO in heme + C60, exhibited in Figure 3(c) has a dxz

configuration, but with lobes rotated by 45◦ in the y direction. Figure 3(c) shows that there is noHOMO on the nanoparticle for heme interacting with C60. The π orbitals of C-C bonds in heme

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097119-6 Wallison Chaves Costa and Eduardo Moraes Diniz AIP Advances 4, 097119 (2014)

alone are changed to a p shape when heme interacts with functionalized fullerenes. Figure 3(c)shows that in heme + C60 HOMO is located around Fe atom, which deviates from other situations,where the entire porphyrin contributes with the HOMO formation.

Regarding the changes in LUMO, all systems have very different orbitals with respect to eachother. Figure 3(d) shows that there is no LUMO on fullerene for heme + C60 while Figure 3(f)shows almost the opposite: a few LUMO states on heme group when it interacts with C60CH3. Theremaining systems, heme + C60COOH, C60NH2 or C60OH exhibit LUMOs in both nanoparticle andheme molecule, as shown in Figures 3(h), 3(j) and 3(l), respectively. For LUMO on heme group,there exist a few π orbitals when it interacts with some functionalized fullerene. When the interactionis with C60, π orbital character of LUMO is predominant, as shown in Figure 3(d).

Although iron does not participate in charge transfers between heme and those nanoparticles,the latter do induce significant changes in HOMO/LUMO near the heme iron, which can partiallyinhibit biochemical processes that depend on the Fe electronic state and influence mechanisms thatrely on whole molecule.

IV. CONCLUSIONS

Heme group interacting with C60 pure or with simple functionalizations was investigated by firstprinciples calculations based on density functional theory using generalized gradient approximationfor the exchange-correlation potential. Quintet was the lowest energy spin state for heme group aloneor interacting with C60 and septet when it interacts with functionalized fullerenes. The second lowerenergy spin state for heme interacting with nanoparticles depends on the fullerene functionalization.Binding energy calculations revealed that heme + C60CH3 is the only system that is not energeticallyfavorable and also that the remaining functional groups provided a stronger interaction between hemegroup and the nanoparticle in comparison with C60, mainly for heme + C60COOH, the most stablesystem. Also one find that geometric distortions of heme group are related with binding energy values.For biological applications, C60CH3 could provide a safer nanoparticle with respect to undesiredinteractions with heme group or C60COOH could be used to deliver some drug to the hemoglobin. Nomolecule was able to move the iron from the porphyrin but there exist conformational modificationson heme geometry. All nanoparticles receive from heme group the same amount of charge, but ironatom does not contribute to this transfer, leaving its oxidation state essentially unchanged, despitethe magnetic moment undergoes variations, which can be explained by spin density surfaces of thenanoparticle near heme iron. Such modifications in magnetic states spreads in heme group, whichcould be observed by the creation of spin up states on heme molecule that did not exist before theinteraction with the nanoparticle. The values of charge transfers for the second lower energy spinstate are very similar, but changes in iron magnetic moment are very different, being three timesgreater than the findings for the lowest energy spin state. As magnetic states are usually presentnear Fermi level, one can expect modifications in HOMO/LUMO wave functions. The interactionwith nanoparticles caused in heme molecule the suppression of some π states and modificationsin d orbitals on C and Fe atoms, respectively. Depending on the nanoparticle, the LUMO waspractically absent in heme molecule. These results suggest that pure or functionalized fullerenesmay not represent large risks for processes that depend on iron oxidation state, but they could reducethe efficiency of biochemical processes that depend on the entire heme molecule due to structuralmodifications, loss of charge and changes in HOMO/LUMO.

ACKNOWLEDGMENTS

The authors thank the Brazilian agencies FAPEMA and CAPES by the financial support.

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