An Atoms-in-molecules (AIM) interpretation of organotin-peptide system: I. Di-n-butyltin(IV) derivative of glycyltryptophane

 

Sandeep Pokharia

Organometallics and Molecular Modelling Group, Chemistry Section, M.M.V., Banaras Hindu University, Varanasi-221005, India.

*Corresponding Author E-mail: sandeepp@bhu.ac.in

The topological and energetic properties of the electron density distribution r for the tin-ligand interaction in di-n-butyltin(IV) derivative of glycyltryptophane (H₂L) (n-Bu₂SnL), the geometric configuration of which was optimized at B3LYP/3-21G/LANL2DZ(Sn) level of theory, have been theoretically calculated at the bonds around the central Sn atom in terms of atoms-in-molecules (AIM) theory using AIMAll(Version16.01.09, standard). In n-Bu₂SnL, the formation of a (3,–1) critical point in the internuclear region between tin atom and bonded/coordinated atoms provided an evidence of a bonding interatomic interaction, and calculated bond path angles indicated a distorted trigonal bipyramidal geometry. The calculated topological and energetic parameters suggested a weak closed-shell interaction in all the bonded/coordinated bonds to Sn atom, as a result this interaction possessed covalent character in Sn–N_amino,Sn–O_carboxyl, Sn–N_peptide, Sn–C_a and Sn–C_a¢ bonds.

 

 

INTRODUCTION:

The chemistry of organotin(IV) complexes is of great interest owing to their structural diversity and wide range of industrial and biological applications.¹ These complexes exhibit expanded coordination upon inter- or intra-molecular interaction with hetero donor atoms owing to the low lying empty 5d atomic orbitals and pronounced electron-acceptor ability of the Sn atoms, thus making them suitable for the design of newer materials with unique structural features.² Further, the antiproliferative activity of these complexes, which is dependent on the nature of coordinated bonds with the central Sn atom has led to a considerable attention towards them. Consequently, several organotin(IV) complexes of dipeptides have been modelled for metal-protein interactions and have been shown to exhibit wide range of biological activities.^3-5

 

These organotin(IV) complexes of dipeptides possess unique structural features in terms of bonding such as, interaction through hetero donor atoms (N/O) as-well-as existence of a distorted geometrical configuration around the central Sn atom. In order to formulate a theoretical basis of these structural features a thorough study of the electronic structure of these complexes is indispensable.

 

In recent years, the atoms-in-molecules (AIM) methodology is commonly used in the modeling of the electron density distribution r in intermolecular interactions.⁶ Though, the topological properties of r have been well established for many molecular systems involving organotin(IV) complexes with hetero donor atoms,^7-10 the studies on the nature of tin-ligand bond in organotin(IV)-peptide complexes is not reported yet. Thus, in order to understand the nature of coordinated bonds, systematic studies have been initiated on topological analysis of organotin(IV)-peptide system. The present study attempts to delineate the topological and energetic features of r using AIM theory, in the coordinated bonds in previously synthesized di-n-butyltin(IV) derivative (n-Bu₂SnL) of glycyltryptophane (H₂L).¹¹ A detailed and systematic density functional theory based quantum-chemical calculations on di-n-butyltin(IV)-glycyltryptophane system has been already presented recently.¹²

(b)

Figure 1: (a) Structure of n-Bu₂Sn derivative of glycyltryptophane (H₂L) (n-Bu₂SnL) along with the atom number notation, and (b) Ground state optimized geometry of n-Bu₂SnL at B3LYP/3-21G/LANL2DZ(Sn) level of theory used for the generation of wavefunction for calculation of topological and energetic parameters in AIM analysis.¹²               

 

Computational Details

The nature of coordinated bonds in n-Bu₂SnL has been interpreted in terms of AIM theory using AIMSum component of AIMAll software package.¹³ The wavefunction input for AIM analysis has been generated from the previously optimized geometrical configuration of n-Bu₂SnL at B3LYP/3-21G/LANL2DZ(Sn) level of theory using the Gaussian 09 program package.¹⁴ The topological and energetic analysis of r has been carried out in terms of (3,–1) critical points (bond critical points) and (3,+1) critical points (ring critical points) around the central Sn atom in n-Bu₂SnL derivative. The parameters obtained at the bond critical points (BCPs) are the electron density (r), the Laplacian of the electron density (Ѳr), the principal curvature of r in the normal plane to the bond path direction (l1_CP and l2_CP), the principal curvature along the bond path direction (l3_CP), bond ellipticity (e), the electron kinetic (G), potential (V) and total (H) energy densities. The bond path angle for a group of atoms has also been calculated in n-Bu₂SnL derivative.

 

RESULTS AND DISCUSSION:

The values of electron density distribution r were calculated on the ground state optimized geometry in gas phase of n-Bu₂Sn derivative of glycyltryptophane (H₂L)(n-Bu₂SnL) at the B3LYP/3-21G/LANL2DZ(Sn) level of theory, and then r was analyzed within the framework of the AIM theory. The structure of n-Bu₂SnL along with the atom number notation and the ground state optimized geometry used for wavefunction calculation for AIM analysis is presented in Figure 1. The insight into the intermolecular interaction of hetero donor atoms in H₂L with n-Bu₂Sn(IV) moiety was obtained from the full topological and energetic analysis of the r at the selected BCPs around the central Sn atom in n-Bu₂SnL derivative. The evidence of a bonding interatomic interaction can be obtained from the topological analysis of  rthrough the formation of a (3,–1) critical point in the internuclear region between the central Sn atom and bonded/coordinated atoms in the trigonal bipyramidal arrangement around it. The bond path corresponding to these critical points link the BCP with two (3,–3) critical points located at the coordinated/bonded atoms and the central Sn atom, thus providing an evidence that, in terms of AIM theory, the group of atoms are bonded to one another.¹⁵ The values of selected AIM topological parameters at these selected BCPs are presented in Table 1.

 

In the internuclear region specifically at the critical point, r measures the interaction strength, and thus greater the value of r stronger will be the interaction.¹⁶Apart from this, the topological properties of r at the critical point also characterize the interaction between the involved atoms, and according to the AIM methodology the classification of this interaction is defined by the sign of the Laplacian Ѳr. Therefore, the strong shared-shell (SS-) interatomic interaction is evidenced by a local concentration of the electron density distribution at the critical point when Ѳr< 0, whereas the weak closed-shell (CS-) interaction exhibit its local depletion when Ѳr> 0. As evident from the results (Table 1), the value of r is small and the Laplacian Ѳr is positive, which suggests a contraction of an electron charge away from the interatomic region between the bonded atom and the Sn atom. According to the r values (Table 1), the bond strength around the central Sn atom increases in the order: Sn–N1_(amino) < Sn–C37_(a) <Sn–C34_(a')<Sn–N9_(peptide)<Sn–O17_(carboxyl). The positive values of Ѳr were often found at the BCP between atoms involved in the dative bonds, including the intramolecular N→Sn,⁷ and O→Sn,⁹  bonds. The magnitude of the curvature or eigenvalue of the Hessian of r in an atomic surface l1_CP and l2_CP are negative, whereas along a bond path l3_CP is positive, a behavior at the BCP around the central Sn atom in n-Bu₂SnL which is in accordance to the fact put forwarded earlier.⁶ Further, the results (Table 1) suggest that all the bonds in the coordination sphere around the central Sn atom involves weak CS-interaction as the magnitude of the ratio of the perpendicular contractions of r to its parallel expansion i.e., |–l1_CP/l3_CP|< 1 (where, l1_CP and l3_CP are the lowest and highest eigenvalues of the Hessian matrix of r).^6,16 Furthermore, the order of ellipticity, e = [(l1_CP/l2_CP) – 1] (Table 1), for the selected BCPs around the central Sn atom is: Sn–N_peptide> Sn–O_carboxyl> Sn–C_a> Sn–N_amino>Sn–C_a', which indicates that the interaction of hetero donor atoms in the ligand (H₂L) results in a weaker bond in comparison to the covalently bonded carbon atoms of the two n-butyl groups in the n-Bu₂SnL derivative.

 

 

Table 1: Topological and energetic properties of r calculated at the (3,–1) and (3,+1) critical point of the selected bonded interactions in n-Bu₂SnL derivative of glycyltryptophane (H₂L) at B3LYP/3-21G/LANL2DZ(Sn) level of theory.^a

Typeb	rc	Ñ2rd	l1CPe	l2CP	l3CP	ef	Gg	Vh	Hi	|V|/ G	H/ rj	–l1CP/l3CP
(3,–1) critical point or Bond critical point (BCP)
Sn–N1	0.0603	0.2330	–0.0677	–0.0673	0.368	0.0052	0.0222	–0.0357	–0.0135	1.6081	–0.2239	0.1839
Sn–N9	0.1095	0.4451	–0.1538	–0.1369	0.7357	0.1232	0.0391	–0.0622	–0.0231	1.5908	–0.2109	0.2091
Sn–O17	0.1125	0.5296	–0.1629	–0.1555	0.8480	0.0478	0.0514	–0.0748	–0.0234	1.4553	–0.2080	0.1921
Sn–C34	0.1034	0.2195	–0.1208	–0.1195	0.4597	0.0113	0.0203	–0.0550	–0.0347	2.7094	–0.3356	0.2628
Sn–C37	0.1031	0.2207	–0.1198	–0.1197	0.4602	0.0009	0.0202	–0.0546	–0.0344	2.7030	–0.3337	0.2603
O8∙∙∙∙∙H14	0.0130	0.0598	–0.0122	–0.0087	0.0808	0.4037	0.0127	–0.0105	0.0022	0.8268	0.1692	0.1510
O18∙∙∙∙∙H21	0.0107	0.0517	–0.0112	–0.0051	0.0679	1.1927	0.0103	–0.0077	0.0026	0.7476	0.2430	0.1649
O8∙∙∙∙∙H27	0.0121	0.0576	–0.0153	–0.0149	0.0878	0.0280	0.0118	–0.0093	0.0025	0.7881	0.2066	0.1743
(3,+1) critical point or Ring critical point (RCP)
N1–C3–C5–N9–Sn33	0.0248	0.1117	–0.0176	0.0298	0.0995	–	0.0279	–0.0282	–0.0003	1.0108	–0.0121	0.1769
N9–C10–C13–O17–Sn33	0.0277	0.1342	–0.0219	0.0416	0.1145	–	0.0336	–0.0339	–0.0003	1.0089	–0.0108	0.1913
N1–H4–H52–C50–C34–Sn33	0.0061	0.0268	–0.0048	0.0042	0.0274	–	0.0054	–0.0041	0.0013	0.7592	0.2131	0.1752
N1–H2–H41–C40–C37–Sn33	0.0063	0.0283	–0.0048	0.0028	0.0303	–	0.0055	–0.0039	0.0016	0.7091	0.2539	0.1584
N9–C10–C12–H15–H42–C40–C37–Sn33	0.0011	0.0046	–0.0003	0.0007	0.0043	–	0.0008	–0.0005	0.0003	0.6250	0.2727	0.0698

^aAll the values are in atomic units; ^bAtom number as represented in Fig. 1(a);^cElectron density distribution at the critical point (CP); ^dLaplacian of the electron density at CP; ^eli_CP (i = 1,2,3) are the eigenvalues of the Hessian of r in ascending order, where l1_CP and l2_CP are the principal curvature of r in the normal plane to the bond path direction and l3_CP is the principal curvature along the bond path direction; ^fBondellipticity = [(l1_CP/l2_CP) – 1]; ^gLagrangian form of kinetic energy density; ^hPotential energy density; ⁱTotal energy density = G + V; ^jBond degree parameter.

 

The AIM energetic parameters at the selected BCPs are also presented in Table 1. The G is less than V for Sn–N_amino, Sn–O_carboxyl, Sn–N_peptide, Sn–C_a and Sn–C_a¢, resulting in the negative sign of the H(= G + V). Since, H< 0 has been suggested as one of the sufficient condition for a covalent bond even though a CS-interaction is involved,¹⁶ thus, all the bonds to the central Sn atom viz., Sn–N_amino, Sn–O_carboxyl, Sn–N_peptide, Sn–C_a and Sn–C_a¢ possess a covalent character. Further, Vand Gare interpreted as the pressures exerted on and by the electrons at the critical point, and hence the ratio |V|/G> 1 for Sn–N_peptide, Sn–N_amino and Sn–O_carboxyl indicates that the interaction is stabilized by a local concentration of the charge.^6,16 Further, the magnitude of the bond degree (BD = H/r)(Table 1) indicates a strong interaction quantifying a covalence degree (d <d_cov) per electron density unit at the BCP for Sn–N_amino, Sn–N_peptide, Sn–O_carboxyl, Sn–C_a and Sn–C_a¢.¹⁶

The structure of n-Bu₂SnL is further analyzed in terms of the formed five (3,+1) critical points (RCPs), thus satisfying Poincare-Hopf relationship.¹³ The topological and energetic parameters for five RCPs are presented in Table 1, which demonstrates a trigonal bipyramidal arrangement around the central Sn atom in n-Bu₂SnL, and weaker CS-interaction between the involved atoms.

The significant aspect of AIM analysis is to understand and analyze hydrogen bonds, which for n-Bu₂SnL indicates presence of three intramolecular hydrogen bond between O18_(carboxyl)∙∙∙∙∙H24, O8_(peptide)∙∙∙∙∙H14 and O8_(peptide)∙∙∙∙∙H27. The Laplacian Ѳr, the H, and H/r for these hydrogen bonds are all positive, hence it can be classified as medium hydrogen bond with partially covalent-partially electrostatic characteristics.¹⁷

The bond path angles for different pairs of three atoms in n-Bu₂SnL have been also calculated using AIM theory, and the results for the selected pairs around the central Sn atom are presented in Table 2. The results indicate a distorted trigonal bipyramidal arrangement around the central Sn atom (Table 2).

 

Table 2:Bond path angles (°) at the selected group of atoms in n-Bu₂SnL at B3LYP/3-21G/LANL2DZ(Sn) level of theory.

Bond Path Angle
A–B–C	Angle
N9–Sn33–N1	74.90
O17–Sn33–N1	154.21
O17–Sn33–N9	79.56
C34–Sn33–N1	91.18
C34–Sn33–N9	118.09
C34–Sn33–O17	104.08
C37–Sn33–N1	88.39
C37–Sn33–N9	119.50
C37–Sn33–O17	101.27
C34–Sn33–C37	119.99
C12–H14∙∙∙∙∙O8	93.64
C19–H21∙∙∙∙∙O18	2.26
C23–H27∙∙∙∙∙O8	170.56

Atom number as represented in Fig. 1(a).

 

CONCLUSION:

The present study demonstrates that all metal-ligand bonds in di-n-butyltin(IV) derivative of glycyltryptophane (n-Bu₂SnL) have coordination (non-sharing) bonding character with a distorted trigonal bipyramidal arrangement around the central Sn atom, thus signifying the importance of AIM theory in understanding the bonding nature in diorganotin(IV)-dipeptide system.

 

ACKNOWLEDGEMENTS:

The author is thankful to Banaras Hindu University, Varanasi for providing necessary infrastructural facilities. Thanks are also due to Dr. H. Mishra, Physics Section, M.M.V., B.H.U., Varanasi for providing access to the Gaussian software package.

 

 

REFERENCES:

1.        Nath M. Toxicity and the cardiovascular activity of organotin compounds: a review. Applied Organometallic Chemistry. 22; 2008: 598-612.

2.        Pellerito L and Nagy L. Organotin(IV)ⁿ⁺ complexes formed with biologically active ligands: equilibrium and structural studies, and some biological aspects. Coordination Chemistry Reviews. 224; 2002: 111-150.

3.        Katsoulakou E et al. Diorganotin(IV) complexes of dipeptides containing the a-aminoisobutyryl residue (Aib): preparation, structural characterization, antibacterial and antiproliferative activities of [(n-Bu)₂Sn(H_-1L)] (LH = H-Aib-L-Leu-OH, H-Aib-L-Ala-OH). Journal of Inorganic Biochemistry. 102; 2008: 1397-1405.

4.        Nath M et al. Organotin(IV) tryptophanylglycinates: potential non-steroidal anti-inflammatory agents; crystal structure of dibutyltin(IV) tryptophanylglycinate. Applied Organometalllic Chemistry. 23; 2009: 347-358.

5.        Girasolo MA et al. New organotin(IV) complexes with L-arginine, N_a-t-Boc-L-arginine and L-alanyl-L-arginine: synthesis, structural investigations and cytotoxic activity. Journal of Organometallic Chemistry. 695; 2010: 609-618.

6.        Bader RFW. A quantum theory of molecular structure and its applications. Chemical Reviews. 91; 1991: 893-928.

7.        Karlov SS et al. Quantum chemical study of group 14 elements pentacoordinated derivatives-metallatranes. Journal of Molecular Structure. 724; 2005: 31-37.

8.        Naseh M et al. DFT studies of ONO Schiff bases, their anions and diorganotin(IV) complexes: tautomerism, NBO and AIM analysis. Computational and Theoretical Chemistry. 1005; 2013: 53-57.

9.        Korlyukov AA et al. Chemical bonding in 1-(chlorodimethylstannylmethyl)-2-piperidone and its Si and Ge analogues. General trends and O→M (M = Si, Ge, Sn) coordination bond energy. Journal of Molecular Structure. 1051; 2013: 49-55.

10.      Matczak P. Theoretical investigation of the N®Sn coordination in (Me₃SnCN)₂. Structural Chemistry. 26; 2015: 301-318.

11.      Nath M et al. New organotin(IV) derivatives of dipeptides as models for metal-protein interactions: in vitro anti-tumour activity. Applied Organometallic Chemistry. 17; 2003: 305-314.

12.      Pokharia S. A Density Functional Theory (DFT) study on di-n-butyltin(IV) derivative of glycyltryptophane. Asian Journal of Research in Chemistry. 9; 2016: 53-61.

13.      Keith TA. AI MAll (Version16.01.09, standard) Overland Park KS, USA. 2016. (http://aim.tkgristmill.com)

14.      Frisch MJ et al. Gaussian 09, Revision B.01, Gaussian, Inc., Wallingford CT. 2010.

15.      Bader RFW. A bond path: A universal indicator of bonded interactions. Journal of Physical Chemistry. 102; 1998: 7314-7323.

16.      Espinosa E et al. From weak to strong interactions: A comprehensive analysis of the topological and energetic properties of the electron density distribution involving X–H∙∙∙∙∙F–Y systems. Journal of Chemical Physics. 117; 2002: 5529-5542.

17.      Nazari F and Doroodi Z. The substitution effect on heavy versions of cyclobutadiene. International Journal of Quantum Chemistry. 110; 2010: 1514-1528.

 

 

Received on 30.12.2016         Modified on 15.01.2017

Accepted on 27.01.2017         © AJRC All right reserved