Accepted Manuscript Binding and selectivity of phenazino-18-crown-6-ether with alkali, alkaline earth and toxic metal species: A DFT study Nasarul Islam, Swapandeep Singh Chimni PII: S0022-2860(16)31136-X DOI: 10.1016/j.molstruc.2016.10.100 Reference: MOLSTR 23101 To appear in: Journal of Molecular Structure Received Date: 15 June 2016 Revised Date: 25 October 2016 Accepted Date: 25 October 2016 Please cite this article as: N. Islam, S.S. Chimni, Binding and selectivity of phenazino-18-crown-6-ether with alkali, alkaline earth and toxic metal species: A DFT study, Journal of Molecular Structure (2016), doi: 10.1016/j.molstruc.2016.10.100. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT Binding and Selectivity of phenazino-18-crown-6-ether with alkali, alkaline earth and toxic metal species: A DFT study Nasarul Islam and Swapandeep Singh Chimni*¶ Department of Chemistry, U.G.C. Centre of Advance Studies in Chemistry, Guru Nanak Dev T University, Amritsar, 143005, India. Fax: (+) 91-183-2258820 P ¶Mentor, Dr. D. S. Kothari PDF. I Email; [email protected] R [email protected] C Abstract S U The interactions of phenazino-crown ether ligands with alkali, alkaline earth and selected N toxic species were investigated using density functional theory modelling by employing B3PW91/6-311G ++ (d, p) level of theory. The comAplex stability was analysed in terms of binding energies, perturbation energies, position of highest molecular orbital and energy gap M values. In general, the complexes formed by P18C6-1a ligand with metal cations were found to be more stable than those with P18C6-1b. Among alkali and alkaline earth metals D complexes having highest stability was observed for the complex formed by P18C6-1a with E Be2+. Computational calculations of P18C6 ligand with toxic metal ions reveals that the T P18C6-Cr6+ metal complexes acquire envelop like geometry, leading to higher binding energy values. Comparing the Pbinding energies of neutral and monocations of Ag and Hg, the former had higher value bEoth in neutral as well as monocation state. Thus, the stability of metal complexes is determined not only by the ligand but also by the type of metal ion. In C solvent systems the stability constants of metal complexes were found increasing with C decreasing permittivity of the solvent. This reflects the inherited polar character of the protic A solvents stabilises the cation, resulting in decrease of effective interaction of ligand with the metal ion. Key words Phenazino-18-crown-6-ether, Electron affinity, Perturbation energy, Macrocyclic Ligand, Dipole moment. ACCEPTED MANUSCRIPT 1. Introduction The discovery of dibenzo-18-crown-6 by Pedersen attracted the attention of researchers to focus on the nature of selectivity of macrocyclic derivatives for metal cations [1]. The selectivity of macrocyclic compounds has often been explained in terms of the size-fit concept, involving either covalent interactions or non-covalent interactions [2-4]. These T compounds are capable of forming complexes with alkali and alkaline earth metal ions via P electrostatic attraction and encapsulation into a suitable cavity [5-7].According to Glendening I et. al., and More et. al., the binding energy studies between crown and alkali metal ions have R shown that the enthalpic stability of the complexes in the absence of a solvent decreases C monotonically with increasing size of the metal ion [8, 9]. This discrepancy between the solution and gas phase results, indicates that the solvation effSects strongly influence the binding selectivity of macrocyclic compounds in solution phasUe [7, 10-12]. N Crown ethers, a class of macrocyclic compounds are well-known host molecules of biological interest; playing a role in biological cAation transport systems and of some antibiotics (such as valinomycin) that also bind mMetal cations selectively [13-18]. According to Makrlik et. al., change in oxidation state of the metal inside the crown ether is useful for creating switching or photoswitching oDf complexes [19]. It was found that silver(I) complexes with diaza-18-crown-6-derivatives can be reduced to zero oxidation state in a E solution medium. Which was used for sensing of polarizable heavy metal cations such as T Ag(I) and Hg(II) [20]. Extensive theoretical studies, particularly ab initio calculations have P been performed on free crown ethers, ammonium and crown ether complexes with alkali and alkaline earth metals [3,5E,13,15]. Anderson et. al., used Hatree-Fock and MP2 level of theory for calculating tChe structure and binding energies of 18-Crown-6 complexes of alkali metals [13]. According to them, the computed order of Li+ affinities at all levels of theory is C 18C6 < 15C5 < DB18C6, and that for Na+ is 18C6 < DB18C6 < 15C5 (RHF) or A 15C5<18C6< DB18C6 (MP2), in contrast to the experiments and earlier calculations. Heo [21] studied the selectivity of D18C6 ether for alkaline earth divalent cations. Based on NBO analysis, he concluded that the large binding energy is attributed to the strong polarization of the C−O bond by cation in solvent phase (aqueous). Among all dications, Mg2+ demonstrates the highest binding energy as compared to its lowest energy gaps in the gas phase, which may be attributed to the large hydration energy for the small size of cation in aqueous medium. Bagatur’yants et. al., reported DFT calculations of the electronic and geometrical structure of 18-Crown-6, its complexes with Ag+, Hg2+, Ag0, Hg+, Hg0, AgNO [22]. According to them 3 ACCEPTED MANUSCRIPT among all studied metal species Hg2+ ion is strongly bound to the crown ether. It was found that silver and mercury ions in the 18-crown-6 cavity gets reduced by capturing an electron within the complexes and nature of bonding in these complexes between the metal and the ligand is van der Waals type interaction. Structural studies on [Cd(18-crown-6)X ] done by 2 Yan et al employing DFT level of theory shows that the binding of axial ligands such as T water with metal ion involves ionic interaction which displays no distortion towards linear geometry of complexes. The geometry predicted for this complex shows thPat the Cd(II) binds to only a few of the donors of the crown ether, with short Cd–O bondIs. In second case R the binding of axial ligands such as Cl in the [Cd(18-crown-6)X2] complex were found more covalent in nature results in the distoration of geometry with short CCd–Cl bonds and long Cd–O bonds to the O-donors of the crown ether [2, 4]. However, no theoretical investigation S on structural and binding interactions has been reported on phenazino-18-crown-6-ether U complexes of alkali and alkaline earth metal cations. N Phenazino-18-crown-6-ether (P18C6) (Figure 1) is the prototype of dibenzo-18-crown-6 A having phenazine instead of dibenzo, carrying one addition planar binding site for guest M molecule. When substituted at C and C these are categorised under chiral crown ethers, 23 26 have received much attention on accoun t of presence of naphthalene wall, which is D supportive in the enantiomeric recognition of optically active amino acids and organic ammonium ions [23-25]. Bradshaw et.E al., prepared a series of chiral crown ethers, aza-crown ethers, and crown ether diesters haTving pyridine, triazole, and pyrimidine subcyclic units to develop qualitative and quantitative relationships between molecular structural features of P chiral crown ether hosts and chiral organic ammonium ion guests [23].The log K values E measured using an1H NMR show that these chiral pyridino-18-crown-6 ligands have high C complexing abilities. However, the investigation on geometrical parameters of pyridino-18- crown-6 ligands dCisplays that in the lowest energy conformers the phenyl ring of the guest PhEt orients pAarallel and perpendicular to the pyridine ring present in chiral dimethyl- substituted ligand complexes and in chiral di-tert-butyl-substituted ligand complex with PhEt respectively. Various structural changes to crown ether hosts have been made in attempts to enhance their complexation stability and selectivity. Some of these modifications have involved the insertion of heterocyclic units or substitution at chiral centres of the macro-ring [24-26]. In this paper computational methods has been employed to address the structural implications and relative binding energies of alkali, alkaline earth and selective ACCEPTED MANUSCRIPT toxic metal cations (Hg, Hg+, Hg2+, Pb2+, Pb4+, Ag, Ag+, As3+, Cd2+ , Cr+6) on the pore size of phenazino-18-crown-6-ether ligand. 2. Computational Method Calculations were performed using Gaussian 09 computational package [27]. Becke’s three- T parameter hybrid functional including a mixture of Hatree–Fock exchange with DFT exchange-correlation combined with Lee-Yang– Parr correlation functional (B3PLYP)[28]and B3PW91[29] were used in all calculations employing 6-311G++ (d, p) (forI C, H, N, O) and R LANL2DZ (Los Alamos effective core potentials) (for metal ions) basis set. B3LYP and B3PW91 are the most widely used hybrid generalized gradient approCximation functional and have been demonstrated in numerous studies to be efficient and reasonably accurate in S predicting interaction and binding energies of organic molecules and inorganic complexes U [30-32]. Vibrational frequencies of optimized structures were calculated to identify probable N imaginary frequencies of the local minimum structures. The binding energy (BE) and electron affinity (EA) were calculated by using the folAlowing equations. M (cid:1)(cid:2) = (cid:2) − (cid:13) (cid:2) + (cid:2) (cid:22) ……1 (cid:4)(cid:5)(cid:6)(cid:7)(cid:8)(cid:9)(cid:10) (cid:6)(cid:9)(cid:14)(cid:15)(cid:8) (cid:16)(cid:5)(cid:17) (cid:19)(cid:16)(cid:20)(cid:15)(cid:17)(cid:21) (cid:2)(cid:25) = (cid:2)(cid:27) D − (cid:2) ………2 (cid:26)(cid:5)(cid:6)(cid:7)(cid:8)(cid:9)(cid:10) (cid:26)(cid:5)(cid:6)(cid:7)(cid:8)(cid:9)(cid:10) E To avoid a basis-set superposition error (BSSE) metal-ligand binding energies (IPBEs) were counter-poise corrected using a sTtandard approach by Boys and Bernardi [33] The final expression for the (BE ) was as follows: BSSE P E (cid:1)(cid:2) = (cid:2)(cid:4) − (cid:2) −(cid:2) +∆"#$(cid:2)…………3 (cid:29)(cid:30)(cid:30)(cid:31) (cid:4) (cid:6) (cid:19) C where (cid:2)(cid:4) is the counter-poise corrected electronic energy of the complex and (cid:2) and (cid:2) are (cid:4) (cid:6) (cid:19) C the electronic energies of the metal ion and the ligand in their minimum-energy geometries A The natural bonding orbitals (NBO) calculations was performed using NBO 3.1 [34] implemented in the Gaussian 03 package. The second order perturbation energies E(2) based on the Natural Bond Orbital (NBO) analysis were calculated from analysis of Fock matrix , which corresponds to the overlap integral of orbital pair[35]. For each donor NBO (i) and acceptor NBO (j), E (2) associated with i→j delocalization is given as: )& ((cid:16),') (cid:2) = ∆(cid:2) = ( ………4 & (cid:16)' (cid:16) - − - (cid:16) ' ACCEPTED MANUSCRIPT Here, ( is the donor orbital occupancy - , - are diagonal elements (orbital energies) and (cid:16) (cid:16) ' F(i,j) are the off diagonal elements of NBO Fock matrix. 3. Results and Discussion 3.1 Geometry of ligand and metal complexes T The lowest energy structures optimised at B3PW91/ 6-311++G (d, p) / LANL2DZ of P phenazino-18-crown-6-ether and its complexes with metal cations are shown in Figure 2 I (Figure S1, S2 and S3). The relative energies and binding energies for the lowest energy R conformer in the gas phase are displayed in Table 1 and Table 2. The optimised geometries of C two derivatives of P18C6 i.e 1a and 1b show difference in planarity. In case of P18C6-1a S oxygen atoms O and O lies in the same plane and the remaining four oxygen atoms are 21 22 U out of plane with a distance of 1.412 Å from the plane of crown moiety. We have observed that all donating groups are towards the cavity on accoNunt of reduced C -O , C -O and 2 21 9 22 trans annular O –O / O –O distances. In addition to it all the four C-O bonds adopt 36 22 35 21 A gauche-conformation with respect to each other. In case of P18C6-1b ligand the methyl M groups occupies either cis or trans position with respect to each other. However in both cis- 1b and trans-1b all the oxygen atoms are oriented in a way that they are coplanar to D phenazine framework. The C-O bonds are homo distant planar, with O atom slight out of 49 E plane from the main framework of crown. In this work we have calculated the binding energies corresponding to the intTeraction of P18C6-1a and cis-P18C6-1b with the alkali, alkaline earth and toxic metals. In the two crown ligands 1a and 1b the C -O and C -O are P 2 21 9 22 slightly longer in the later as compared to former. This is due to the presence two methyl E groups on 1b. In both the case the hydrogen atoms are oriented away from the crown cavity, C resulting in eclipse conformation of the neighbouring hydrogen atoms. The optimised struCctures of the P18C6.M+ complexes determined at B3PW91/6-311++G (d, A p)/ LAN2DZ are shown in Figure 2 (Figure S1 and S2). The geometry of both P18C6 crown shows least relaxation on forming complexes with alkali metal ions. The Li+ and Na+ complexes of P18C6-1a show structural resemblance and acquired different geometry from the K+, Rb+ and Cs+ complexes. P18C6.M+-1a (M+ = Li+ and Na+) have twisted geometry, in which O along with two neighbouring CH groups comes out of the plane of the core, 49 2 occupying perpendicular position to metal ion as compared to free P18C6 ligand. The C -O 32 36 and C -C bond lengths are 1.473Å and 1.574 Å in free ligand and changes to 1.451 Å and 40 46 1.561 Å in complex respectively, with a change in bond angle (<C O C ) of 14°. The metal 32 36 40 ACCEPTED MANUSCRIPT ion ( Li+ and Na+ ) tends to occupy central position of core, remaining coplanar to O NO 21 22 plane at a distance of 2.060 Å from Nitrogen atom and 2.091 Å form Oxygen atoms. The P18C6-1a complexes of K+, Rb+ and Cs+ acquires boat-shaped structure with metal ions lying above the mean core of the donor oxygen atoms. The computational studies revealed that the height of metal ion from the plane of core increases with increase in the ionic radius of metal. In these complexes the ligand species relax the (<C O C )angles fromT 1070 to 32 36 40 1130 with maximum in case of P18C6Cs+. In the complex P18C6Cs+ all fiveP donor groups including four oxygen atoms and the nitrogen of phenazine comes almost inI similar plane. In R general as compared to the free crown ether, the C-C bond in the P18C6-1a alkali metal complexes is shortened and the C-O bonds are lengthened. C In case of P18C6.Li+-1b and P18C6.Na+-1b complexes, the bonds corresponding to C -O - S 32 36 C and C -O -C orients above the metal ion and perpendicular to the oxygen and nitrogen 40 29 35 37 U group of ligand. The metal ion occupies a tetrahedral position to NO O O with a dihedral 22 36 49 N angle O M+NN` of 46°.The P18C6.M+-1b (M = K+, Rb+ and Cs+) have planar geometry with 49 A metal ion above the plane of ligand. The planarity of ligand increases with increase in the size of metal ion with maximum metal-donor Mplane distance in case of P18C6.Cs+-1b. Compared to other complexes in the lowest conformer energy of P18C6.Cs+-1b, Cs+ and methyl groups occupies the positions on theD opposite side of core plane. DFT calculated structures of P18C6.EM+2-1a and 1b (M=Be2+, Ca2+, Mg2+ Sr2+ and Ba2+) complexes are given in Figure 2 (FTigure S2). In case of P18C6Be2+ -1a and 1b complexes, the macrocyclic ligand forms a twisted geometry around the central metal ion. The macrocyclic P framework results in the arrangement of donor atoms O , O and nitrogen in plane with the 21 22 E metal ion forming a distorted square planar view. The rest portion of ligand maintains C distorted square pyramidal coplanar geometry with respect to phenazine plane. In both the complexes (P18C6CBe2+-1a and P18C6Be2+-1b) the hydrogen atoms present on the pyramidal portion of ligaAnd orients in gauche conformation with adjacent hydrogen and in eclipsed conformation to hydrogen present on planar core carbons. In case of complexes P18C6M2+- 1a and P18C6M2+-1b (Mg2+, Ca2+, Sr2+ and Ba2+) the ligand framework orient in a planar view with metal ion above the main plane of the donor atoms. It has been observed that the ligand flattens with increasing metal size and increase in distance from metal cation to the donor groups as the metal is varied from Mg2+ to Ba2+. This increase in the M-O distance may indicate the weakening of the bonds between the metal cation and the oxygen atoms, due to geometrical relaxation of ligand on account of size specificity of these metal ions. ACCEPTED MANUSCRIPT In case of Cd2+, Pb2+ and Hg2+ P18C6M-1a and P18C6M-1b metal complexes the metal ion is coordinated with all the donor groups in an asymmetric manner (Figure 2 and Figure S3). The donor atoms O , O and N remains in planar geometry and rest donor groups acquire a 21 22 pyramidal position with respect to metal ion defining a square pyramidal geometry around the dication. It is interesting to observe that the ligand P18C6-1a displays an envelope like T geometry around the Cr (VI) cation. The metal ion remains equidistant from donor groups N, O21, O22 at a distance of 2.401Å and from O35, O49, O36 at a distance 2.351, ÅP respectively. The Oxygen atoms O , O and nitrogen forms base of envelop and the reImaining oxygen 21 22 R atoms O , O and O reorganises to form flap of envelop. However, P18C6Cr6+-1b 35 49 36 complexes have distorted geometry with oxygen atom occupying pyCramidal position. Thus, in former case it can be suggested that the pore size of P18C6-1a allows metal ion to interact S with O , O and O atoms. This results in polarization of localized electron density on 35 49 36 U ligand towards metal cation. In this complex the shared electrons between interacting oxygen N atoms and Cr6+ions get closer to oxygen atoms, and the distance between Cr6+ and N atom A elongates. On the other hand, the oxygen atoms O , O and O attracted more electron 35 49 36 density from two adjacent atoms which cause Mthe other bonds to become stronger and therefore shortened, hence enhancing the stability of the complexes. In case of ligand complexes containing As3+ Hg1+, Ag1+ anDd Pb4+ both the ligand remains slightly distorted from the metal plane as compared to complexes of Hg and Ag, where the ligand is flatten E with metal ion equidistant from all the donor groups. It has been observed that due to the C v 2 T symmetry of ligands P18C6-1a and P18C6-1b in the Hg and Ag complexes the cation has the P flexibility to move along the C axis, but must remain equidistant from either donor oxygen 2 atoms or donor nitrogen atoEm of the macrocyclic framework. C 3.2 Binding energies of ligand and metal complexes C To gain insights in to the extent of interaction of metal ion with the ligand moieties we A calculated the binding energies using DFT/B3PW91 level of theory. The observed values of binding energies in the gas phase decreases down the group both in case of alkali and alkaline earth metal complexes with P18C6M+/2+ (Table 1). The computed values of binding energies in this study for K+, Rb+, Ca2+ and Mg2+ are in close agreement with the experimental values [2-4, 13]. Comparing the binding energies of alkali and alkaline earth metal complexes with both the crown ligand shows that the former has higher values as compared to the latter. The higher values of polarizability for P18C6 -1b favours enhanced interaction with metal ions (higher binding energies) than P18C6-1a, but presence of two additional methyl groups make ACCEPTED MANUSCRIPT it much more rigid therefore decreasing the possibility of geometry relaxation for accommodating the incoming metal cation. In addition to it due to presence of two methyl on P18C6M+/2+ the metal cation like Li+, Na+, Mg2+ and Ca2+ does not interact with all the donor site, due to geometrical constraints of macrocyclic framework. This results in lower value of binding energies of P18C6 -1b (M+ /M2+) as compared to P18C6-1a (M+ /M2+) T ligand complexes respectively. Among alkali and alkaline earth metals the binding energy values define the greater affinity of ligand P18C6-1a for Be2+. This is attributPed to the pore size specificity of ligand for Be2+, which allows it to simultaneously interaIct with nitrogen R and three coplanar oxygen atoms of the crown cause reorganisation of ligand frame work. Thus, reorganisation results in reduction of the overall energy of P18CC6-1a (Be2+) complex. The higher value of binding energy of metal ions (Table 2) for liSgand P18C6-1a indicates its enhanced sensor sensitivity for the studied toxic ions as comUpared to the ligand P18C6-1b. We have observed that the calculated binding energies of equally charged ions are close in N value. The metal ligand binding energies were found strongly depended on the formal A charges of the metal ion with highest in case of Cr6+. The binding energies display well M correlation with ionic radii and shows linear dependence on ionic radii of corresponding metal cations (Figure 3). Enhanced value o f binding energy for P18C6Cr6+-1a complexes D correlates well with stability of complexes gained by ligand reorganisation around the specific Cr6+ ion. In the formationE of P18C6Cr6+-1a the modified geometry allows considerable electron density transTfer from O and O to the metal and this electron density 35 36 makes a significant contribution to the metal–ligand interaction which results in overall P decreases in energy of P18C6Cr6+-1a complex. Comparing the binding energies of Ag and E Hg as neutral and monocations, the former had higher value both in neutral as well as C monocation state. This is due to enhanced Pauli repulsion in case of Hg on account of addition s-electronC in outer shell. A 3.3 Frontier molecular orbital and Natural bond orbital analysis P18C6 has a band gap of about 3.4165eV substituting hydrogen atom with methyl groups enhances the band gap to 3.4565 eV which is not significant change. On complexation with the metal cations both the ligand moiety shows decrease in the energy gap down the group. According to Fleming larger values of the energy difference (∆E) between E – E , LUMO HOMO present low reactivity to a chemical species and hence more stability and lower values of the energy difference show higher reactivity, thus results in less stable molecule [36]. From table ACCEPTED MANUSCRIPT 3, the ∆E of P18C6 Be2+-1a has higher values than all other P18C6 M2+-1a metal complexes which means that the complex P18C6 Be2+-1a have lower reactivity and hence more stable than P18C6 M2+-1a complexes. Among the studied toxic metal complexes the Cr6+ complexes display higher value of energy gap (∆E) followed by Cd2+ and Ag+ the remaining complexes follow the order Hg2+ > Pb2+ > Hg > Ag > Pb4+ > As3+ . This confirms the ligand selectivity of Cr6+ and Cd2+ towards crown ether P18C6-1a species, defining the stabilitTy of said complexes in gas phase. The FMO studies of studied metal complexes (Figure 4P) reveals that, in the free ligand the HOMO is primarily located over phenazino-crown inIcluding O and 21 R O , and in complexes with alkali metal the HOMO does not shift, while it shifts towards 22 metal ion in the case of alkaline earth metals and toxic metal coCmplexes. The value of electron affinity (calculated from single point energies) for ligand P18C6-1a (-0.581eV) at S 298 K and 1 atm were found more positive value than P18C6-1b (-0.696eV) displaying U stronger tendency of P18C6-1a towards complexation with metal cations. N The NBO analysis reveals an interesting interaction in P18C6-1a involving A hyperconjugation of lone pair of oxygen atom with non-Lewis orbital of C-H bond (n - O M σ* ) indicating existence of internal hydrogen bonding. There are fourteen n -σ* CH O CH interaction present in P18C6-1a of them fou r showed hydrogen bonding. However, only ten D such interaction are present in P18C6-1b with two hydrogen bonds, displaying more stability of former ligand instead of more rigiEd structure of latter. The E2 (second order interaction energies) corresponds to the intensTity of charge transfer interaction between Lewis donor and non-Lewis acceptor NBO obtained from NBO analysis. It is clearly indicated that the P maximum donation and the maximum back-donation NBO contribute toward the binding E selectivity. The lone pair electron (LP) of donor atoms and the antibonding lone pair electron C (LP*) of the metal is mainly responsible for E2 values (table 5). For instant in the case of P18C6M+-1a comCplex, the main contribution for E2 is the orbital donor and acceptor from lone pair LP NA4, O21 and O22 and antibond-lone pair LP*(M+). In case of P18C6M+-1a complexes the maximum second order interaction energies E2 decrease in the order Li+ (37.31kcal/mol) > Na+ (36.23 kcal/mol) > K+ (34.79 kcal/mol) > Rb+ (34.38kcal/mol) >Cs+ (33.26 kcal/mol) and in case of P18C6M2+-1a complexes the E2 follows the trend Be2+ (39.11kcal/mol) > Mg2+(37.29 kcal/mol) > Ca2+ (36.71 kcal/mol) > Sr2+ (35.91 kcal/mol) > Ba2+ (34.63 kcal/mol) . The maximum values of E2 from donor atom O O and N 21 22 contribute higher toward complex stability than the maximum E2 values from remaining crown ether oxygen atoms explain the extra stability of P18C6Be2+-1a complexes compared