Experimental and Quantum Chemical Modeling Studies of the Interactions of l-Phenylalanine with Divalent Transition Metal Cations

Abstract

Encoded by the UUU and UUC codons of the genetic code, L-phenylalanine (LPA) serves as an important precursor for tyrosine and various other compounds that are necessary to support life on earth. Here, we report the synthesis (both in solid and solvent phases) and characterization of the Ni(2+), Cu(2+), and Zn(2+) complexes of LPA by several analytical, spectral, thermal, and electrochemical techniques. The results reveal that the products formed by following the two synthetic approaches are the same, and the metal ions bind to the LPA molecules in a 1:2 molar ratio (M(+2)/LPA). Complementary geometries of the metal complexes are modeled involving the most predominant LPA conformers predicted at the MP2/6-311++G(d,p) level. The gaseous and aqueous phase interaction enthalpies and free energies; theoretical IR and UV-vis spectra; HOMO-LUMO energy gaps; dipole moments; Wiberg bond indices as well as the partial atomic charges in LPA and its metallic complexes are calculated and evaluated using B3LYP/6-311++G(d,p) as the main computational method. This study also incorporates analyses on the efficacy of the DFT-D2 level in describing dispersion contributions, performance of the BHandHLYP functional for the open-shell Cu(2+)-LPA system, and relative metal binding affinities of the singlet versus triplet states of the Ni(2+)-LPA complex. Metal-π interactions established via the aromatic side chain of LPA add to the thermodynamic stability of the complexes, whereas metal coordination induces considerable intrinsic structural rearrangements in the molecular geometry of LPA. The LPA binding affinity order of the three Lewis acids investigated emerges as Cu(2+) > Ni(2+) > Zn(2+), paralleling the Irving-Williams series. The illustrative evidence offered by the present work suggests that the B3LYP/6-311++G(d,p) level in combination with an empirical dispersion-correction term performs well in describing the vibrational frequencies and cation-π interactions, which are undoubtedly of immense significance for natural sciences.

A combined experimental and quantum mechanical investigation on some selected metal complexes of l-serine with first row transition metal cations

“…The metal complexes of L-Ser with the doubly charged metal cations of nickel, copper and zinc were prepared according to the method mentioned in the literature [29]. Copper(II) acetate monohydrate (Laboratory Reagent), Nickel(II) acetate tetrahydrate (Laboratory Reagent), Zinc(II) acetate dehydrate (Himedia), L-serine (Himedia) as well as the other reagents used in the experiments were analytical reagent grade obtained from commercial sources.…”

“…The hydrated forms of the metal acetates were converted to their anhydrous forms by drying at 110°C [29]. The metal acetates and L-Ser were ground separately at room temperature for about 15 min in an agate mortar and pestle.…”

“…Since the Ni(II) ion is known to exist in both low-and high-spin states in its complexes, theoretical calculations were carried out for both the singlet and triplet states of the solvated L-Ser complex of Ni(II). The BHandHLYP functional [32] in combination with the 6-311++G(d,p) basis set was also being used for the solvated L-Ser complexes of Ni(II), Cu(II) and Zn(II) ions, since this functional was shown to efficiently ascribe the spin-delocalized situations in an open-shell system like the Cu(II) complex of L-phenylalanine [29]. The reliability of the 6-311++G(d,p) basis set [33,34] in accurately predicting the physicochemical properties of the Ni(II), Cu(II) and Zn(II) complexes of with biologically important chemical species has been exemplified [29].…”

“…The BHandHLYP functional [32] in combination with the 6-311++G(d,p) basis set was also being used for the solvated L-Ser complexes of Ni(II), Cu(II) and Zn(II) ions, since this functional was shown to efficiently ascribe the spin-delocalized situations in an open-shell system like the Cu(II) complex of L-phenylalanine [29]. The reliability of the 6-311++G(d,p) basis set [33,34] in accurately predicting the physicochemical properties of the Ni(II), Cu(II) and Zn(II) complexes of with biologically important chemical species has been exemplified [29]. The accuracy of self-consistent reaction field (SCRF) model in predicting structure and energies of biologically important molecules has also been well documented [35].…”

“…It has now been widely accepted that computational techniques are indispensable in elucidating atomic level structural information about biologically active molecules owing to certain limitations of experimental techniques as pointed out in the literature [26,27]. Experimental investigations carried out in close conjunction with theoretical calculations constitute a more efficient way of assembling atomic level information about the physicochemical properties of bio-molecular systems [26,28,29].…”