Melamine Metal(Ⅱ)-Porphyrin Complexes

1、Structure, Spectroscopy, and Reactivity Properties of Melamine Metal()-Porphyrin Complexes: A DFT、TD-DFT and Conceptual DFT StudyAiguo Zhong*, a Guoliang Dai a Hua Yan a Yanxian Jin a Junyong Wu a (a Department of chemistry, Taizhou College, Linhai Zhejiang , P.R.China 317000;AbstractPorphyrin is a

2、key cofactor of hemoproteins. Its complex with divalent metal cations such as Fe, Mg and Mn is an important category of compounds in biological systems, serving as the reaction center for a number of life essential processes. By employment of density functional theory (DFT) and Conceptual DFT approa

3、ches, structure and reactivity properties of (melamine)n-M-porphyrin complexes are systematically studied for a selection of divalent metal cations with M = Mg, Ca, , Mn, Co, Ni, Cu, Zn, and n = 0, 1, and 2. Metal selectivity and specificity of porphyrin is investigated from the perspective of both

4、structural and reactivity properties. Quantitative structure and reactivity relationships have been discovered between bonding interactions, charge distributions, and DFT chemical reactivity descriptors. These results are beneficial to our understanding of chemical reactivity and metal cation specif

5、icity for heme-containing enzymes and other metalloproteins alike.Melamine and melamine metal complexes are both important pre-compounds of induced stones in humen body The idea to combine the computationally investigated in this work. By employment of density functional theory(DFT), conceptual DFT,

6、 and time-dependent DFT approaches, structure, spectroscopy, and reactivity properties of melamine(L) and its metal complexes(ML, M=Ca, Mg, Fe, Cu, Zn, Ni) are systematically studied for as election of divalent metal ions.We found that ML are structurally and spectroscopically different from their p

7、recursors and ML are more reactive in electrophilic and nucleophilic reactions. A few quantitative linear/exponential relationships have been discovered between bonding interactions, charge distributions, and DFT chemical reactivity indices.These results are implicative in chemical modification of m

8、elamine complexes and understanding chemical reactivity melamine induced stones in human body.Keywords : Melamine; Melamine metal complexes; DFT; TD-DFT; Conceptual DFT1. IntroductionHemoproteins such as hemoglobin1,2, myoglobin3,4, hemocyanin5-7, and neuroglobin8 are among the best understood prote

9、ins in terms of structure, function, and evolution in protein families, because of their abundance in nature and their unique and essential roles they play in physiological processes as sensors, activators, and carriers of the gaseous molecules.9-10 As the core cofactor of hemoproteins, heme is a me

10、tal-binding porphyrin consisting of heterocyclic organic ring made from four pyrrole subunits linked via methine bridges and serving as a prosthetic group for many biological processes, including oxidative metabolism11-13, xenobiotic detoxification, synthesis and sensing of diatomic gases, cellular

11、differentiation, gene regulation at the level of transcription, protein translation and targeting, and protein stability. In its most common form, hemoglobin in the oxygen-binding state for instance, the bonded metal cation is a divalent iron. Other prophyrin-binding divalent metal ions have also be

12、en found such as Mn (chloroperoxidase)14, Mg (chlorophyll)15, Zn (Zn-protoporphyrin IX)16, Cu (hemocyanins)17, etc. When in the rest or functioning state, up to two axial ligands are required to bond with the metal cation in the metal-porphyrin complex to carry out the catalytic process. The most co

13、mmon axial residues in hemoproteins are histidine and cystein.In the present work, we explore the metal-binding selectivity and specificity of porphyrin from the perspective of structure and reactivity properties To that end, together with conventional density functional theory (DFT), we employ the

14、framework of Conceptual DFT, which has been of recent research interest in the literature to understand chemical reactivity26-28. The ultimate question we want to answer is the following: What are the structural or electronic or stereoelectronic factors contributing to porphyrins specific metal ion

15、binding capability to perform biological functions in physiological conditions? In this work, we address a less demanding inquiry: in gas phase in vacuum, can we observe any behavior differences in structure and reactivity descriptors from Conceptual DFT for the porphyrin complexes in bonding with d

16、ifferent metal cations and axial ligands?2. Computational DetailsFollowing eleven divalent metal cations will be employed in this study for the porphyrin-M(II) complex, with M = Fe, Mg, Ca, Mn, Co, Ni, Cu, Zn. To study the impact of the axial ligands on structural and electronic properties of the co

17、mplex, we use the six-membered-ring Mel (Melamine) for the purpose, with which we will consider the following three cases as the axial-binding models (Scheme 1), with no, one and two pyridines axially bonded to the metal cation in the porphyrin inner cavity, denoted by p0, p1, and p2, respectively.I

18、n Conceptual DFT,26 chemical potential and global hardness are defined as the following derivatives, and , respectively, where E is the total energy of the system, N the number of electrons, the external potential, and c electronegativity. According to Mulliken,29 one has and with I and A as the fir

19、st ionization energy and electron affinity, respectively, which can be approximated by the HOMO and LUMO energies via I-HOMO and A-LUMO30. Electrophilicity index,31 a measure of the lowering of the total binding energy because of the maximal electron acceptance can be expressed in terms of and , . O

20、ther Conceptual DFT quantities nucleofugality En and electrofugality Ee,32 are defined as follows: and .These global reactivity descriptors from the conceptual DFT framework, , , , En and Ee, will be used to appraise the global chemical reactivity of our systems.To describe regioselectivity tendenci

21、es of individual atoms in molecules, local descriptors are to be employed. The first well-known example of such a category is called Fukui function,26,27,33 defined as where r(r) is the electron density. Yang and Mortier34 have proposed that for systems with electron gain, the condensed Fukui index,

22、 , in the finite difference approximation is the measure of the nucleophilic attack, where qk(N) is the gross atomic charge for Atom k with N electrons, obtained from a population analysis such as NBO analysis. For systems with electron donation, the condensed Fukui index is susceptible to electroph

23、ilic attack with . For radical attack reactions, , where qk(N+1), qk(N) and qk(N-1) are the gross NBO population on Atom k in a molecule with N+1 (anion state), N (neutral state) and N-1 (cation state) electrons, respectively. Very recently, a new kind of reactivity indices, called dual descriptor,

24、has been proposed,36 which severs as “an indicator for both the nucleophilic and electrophilic regions of a molecule”. Morell, Grand, and Toro-Labbe proposed the first dual descriptor using the cross-term third order derivative , and under the finite difference approximation, one has . The dual desc

25、riptor, f(2)(r), will be positive in electrophilic regions as LUMO(r) is large, and negative in nucleophilic regions as HOMO(r) dominates the regions.Besides the global and local descriptors from conceptual DFT, we will also employ NBO analysis37 to perform the second-order perturbation analysis to

26、understand the bonding features between metal cation and the porphyrin ring and between the metal cation and the axially-bonded pyridine groups. All calculations have been performed with the B3LYP38-39 functional and a compound basis set, where for C and H elements we used 6-31G basis set and N, O a

27、nd metal elements (M=Mg, Ca, Mn, Co, Ni, Cu, Zn) we employed Poples 6-311+G(d) basis set.40,41 This generic basis set 42 has been shown earlier to be effective,43 both efficient and reliable, in predicting structural and reactive properties for heme-like systems. For each system, we first performed

28、tight structural optimization, followed by a frequency calculation to check that the optimized structure was indeed a minimum (with no imaginary frequency). Single-point frequency calculation and NBO analysis were carried out with tight SCF convergence and ultrafine grids using the optimized structu

29、re. For metal ions with different spin states, different multiplicities were examined and the spin state with the lowest energy was then chosen for the subsequent study. Effectiveness of the present approach to deal with spin multiplicity issues under the framework of DFT has been addressed earlier.

30、44 All calculations were performed using Gaussian 03 package.453. Results and DiscussionTable 1 shows a few key structure parameters of the three classes of (Melamine)n-metal-porphyrin complexes (Scheme 1) with eleven different divalent metal ions and different numbers of axial pyridine groups (n=0,

31、1,2). Also shown in the Table are the multiplicity of the lowest energy spin state 44 and the divalent ionic radius of the metal cation. One observes that for the majority of complexes the distances between the metal cation and porphyrin nitrogen atom bond, M-N(Pph), between the metal ion and pyridi

32、ne nitrogen atom bond, M-N(Mel), and between the metal ion and porphyrin plane, M-Plane, for p0-p2 classes are close to each other, around 2.0, 2.2, and 0.0 , respectively. The exceptions are Ca and ions, whose M-N(Pph) and M-Plane distances are much longer than those of other complexes. For example

33、, in the p0 case, Ca does not like to stay inside the inner cavity of the porphyrin ring, lying out of the porphyrin plane by 0.874 . After one pyridine group binds axially to the metal ion in the p1 case, the Ca ion moves further away from the porphyrin ring, preventing the second pyridine group fr

34、om axially binding from the other side of the porphyrin ring to the metal ion. Figure 1 shows the optimized structures for the p1 system of Ca-porphyrin and Fe-porphyrin complexes, where one can see that the main differences between the two structures lie in that (i) the Ca cation in Fig. 1a stays o

35、utside of the porphyrin plane whereas in Fig. 1b, the iron ion resides inside the inner cavity of the porphyrin plane and (ii) the pyridine ring of the Ca structure in Fig. 1a is leaning towards the carboxyl groups whereas in Fig. 1b the pyridine ring holds at the upright position perpendicular to t

36、he porphyrin plane.This large M-Plane distance of Ca complex explains why no stable p2 complex has been obtained in our calculations for these two metal ions.Another structural feature of the (Melamine)n-metal-porphyrin system is the orientation of the pyridine ring relative to the porphyrin plane.

37、In both p1 and p2 cases, the axially bonded pyridine ring is perpendicular to the porphyrin plane.The most common porphyrin binding metal ion in nature is iron. Does Table 1 provide any structural information about why iron is favored? From bond length data, no apparent pattern can be identified. Ho

38、wever, we find that the one major difference between Fe and other metals in the Table is the multiplicity change from open-shell in p1 to close-shell in p2. No other metal ion in Table 1 experiences such an open-to-close-shell transition from p1 to p2, although we noticed the same change for Ru from

39、 p0 to p1. Whether or not this spin-state related effect 44 is unique to iron and whether or not this change is essential for porphyrin complexes to properly function in physiological conditions remain to be investigated in future studies. But as will be shown below from NBO analysis and Conceptual

40、DFT descriptor results, the iron-porphyrin complex does demonstrate some unparalleled behaviors in comparison with other metal complexes in electronic structure and reactivity properties.Table 2 exhibits the charge distribution for a selected list of atoms obtained from the NBO analysis.37 Also show

41、n in the Table are the donor-acceptor back-bonding interactions for pairs like porphyrin (donor) metal (acceptor), metal (donor) porphyrin (acceptor), etc., obtained from the second-order perturbation theory analysis of the Fock matrix in the NBO basis, which provides the hyperconjugation or back-bo

42、nding interaction energies between different chemical motifs in a complex. From the Table, one finds that positive charges on Mg, Ca, Zn are relatively larger than others, and their corresponding N(Pph) atoms are more negatively charged, indicating that the M-N(Pph) bond is more ionic for these bond

43、s. On the other hand, Fe, Co, Ni ions, and their corresponding N(Ppy) atoms have relatively smaller NBO charges, meaning that these M-N(Pph) bonds possess a relatively larger component of covalent bonding. Taking a look of the charge change from p1 to p2 on the metal ion, we notice that for most of

44、the complexes no much variation takes place during the transition, with charge changes on metals all less than 0.1. The two exceptions are Fe and Ru with the charge decreased by about 0.4 and 0.2, respectively, from p1 to p2. Since p2 is the state for porphyrin complexes to undertake catalytic funct

45、ions in proteins, this large reduction of charge on the heme reaction center may well be a prerequisite of the catalyst, thus providing clues on why Fe ion is favored over others by porphyrin metalation in hemoproteins.Also shown in Table 2 are the donor-acceptor back-bonding interactions between po

46、rphyrin and the metal ion, PphM (porphyrin as donor and metal as acceptor) and MPph (metal as donor and porphyrin as acceptor), and between pyridine and the metal ion, PyM (pyridine as donor and metal as acceptor) and MPy (metal as donor and pyridine as acceptor). The general trend is that these int

47、eraction energies are larger for transition metals such as Fe, Co, and Ni and smaller for those without d electrons, e.g., Mg and Ca, or whose d orbitals are full like Zn. Large backbonding energies from the fifth-period Ru complex account for the fact that it has smaller charge distribution and lar

48、ger covalent contributions. Looking at the M Py and Py M energies of the first-row transition metal ions for p2, we find that Fe has the largest sum of these back-bonding interactions. This strong interaction between Fe ion and axial ligands elucidates why there is a substantial decrease of the NBO

49、charge on Fe from p1 to p2. This substantial enhancement of interactions in p2 may also be an indication of the uniqueness of this metal ion in forming complexes with porphyrin.In Fig. 3, we plotted four linear relationships between the charge distributions of metal ions M and porphyrins nitrogen at

50、oms. Basically, ionic bonds have larger positive charge on M and more negative charge on N-Pph, representing data points such as Mg, Ca and Zn at the top right of the lines, whereas for more covalent bonding featured systems, the metal ion and nitrogen atom are less charged so the data points such a

51、s Ru and Fe sit at the low left corner of the lines. From the lines in Fig. 3, we find that these charges distributions among different systems correlate well with each other. One outlier in Fig. 3d is Fe, for which, as mentioned earlier, because of the enhanced back-bonding interaction between Fe a

52、nd axial pyridine groups, one observed a drastic change in NBO charge.Global descriptors from Conceptual DFT including HOMO/LUMO, chemical potential, hardness and electrophilicity index for the three classes of metal-porphyrin complexes are tabulated in Table 3. We find that the HOMO and LUMO energi

53、es do not change markedly with different metal complexes within each class of the compounds, except Mn, whose HOMO energy is much higher than others likely due to its higher multiplicity. Because HOMO and LUMO energies are similar among different metal complexes in each category, so are the other Co

54、nceptual DFT descriptors derived from them. However, from p0 to p1 and p1 to p2, as can be seen from the average value (the last column of Table 3), one finds that both HOMO and LUMO energies become monotonically higher, leading to, averagely speaking, that chemical potential becomes higher, hardnes

55、s smaller and electrophilicity index smaller. Since hardness is an indication of molecular stability, the smaller the hardness the less stable the system becomes, this average picture of p0 to p1 to p2 transitions displays that the system becomes more reactive as more axial ligands bind to the metal

56、 ion inside the porphyrin ring. On the other hand, the smaller average electrophilicity value in Table 3 suggests that the system at the meanwhile also becomes less reactive in accepting electrons. These results from hardness and electrophilicity seem to be paradoxical: the system becomes less stabl

57、e from p0 to p2 but less reactive in accepting electrons at the same time. As will be discussed below with dual descriptor, the reactivity that matters most to the metal-porphyrin complex in carrying out proper catalytic functions in proteins is not electrophilicity, but nucleophilicity, the capabil

58、ity of donating electrons, since in early steps of its catalytic loop, divalent Fe(II) will be oxidized to Fe(IV).For Fe complexes, from p0 to p1, Conceptual DFT descriptors follow the average pattern, with HOMO/LUMO and m increased and h and w decreased. Figure 4 shows the HOMO and LUMO contour sur

59、faces for p0 and p1, from which it is observed that the shapes of LUMO do not change considerably during the transition and it is the HOMO that we find substantial differences between p0 and p1, consistent with the analysis from the second-order perturbation theory result and nucleophilic nature of its reactivity. Deviations from the average picture in Table 3 are seen for the p2 Fe complex where a much smaller w and relatively larger h is observed, which suggests that, compared