Why Does the Coordination Mode of Physiological Bis(L‐histidinato)copper(II) Differ in the Gas Phase, Crystal Lattice, and Aqueous Solutions? A Quantum Chemical Study

Abstract

In bis(L‐histidinato)copper(II), the amino acid L‐histidine can bind to copper(II) in glycine‐like (G), histamine‐like (H), and imidazole–propionic acid like (I) coordination modes. This complex is known as the predominant copper(II)–amino acid complex in human blood serum. Numerous experimental studies of this physiological complex reported several coordination modes to coexist in aqueous solutions, but without providing complete structures. This paper is the first to investigate the relative stability of all possible copper(II) coordination modes and conformations of isolated bis(L‐histidinato)copper(II), and several conformers surrounded with up to 22 water molecules by DFT/B3LYP calculations. The vibration wavenumbers of four bis(L‐histidinato)copper(II)·20H2O structures were calculated and assigned for IR and Raman spectra. Among 83 isolated conformers obtained, 37 are in trans configuration, 45 in cis configuration, and one exhibits a trigonal‐bipyramidal structure. The most stable isolated conformer has a trans‐GG coordination. A comparison between the known X‐ray crystal and B3LYP vacuum molecular structures of bis(L‐histidinato)copper(II) dihydrate showed that the X‐ray cis‐HG mode with an intramolecular apical Cu–Ocarboxylato bond is unstable under vacuum and thus is greatly affected by crystal‐lattice effects. In the systems with 20 water molecules, the lowest energy was estimated for the conformer with a cis‐HH coordination and two axial Cu–Ocarboxylato bonds. This structural finding complements previous experimental studies, which reported an HH coordination mode as the prevailing in aqueous solutions under physiological conditions. The axial Cu–Ocarboxylato bond, unformed in any of the 83 isolated conformers, is stabilized by intermolecular interactions. The arrangement of water molecules around the complex might affect the coordination mode formation and stability.

The Important Role of the Hydroxyl Group on the Conformational Adaptability in Bis(l-threoninato)copper(II) Compared to Bis(l-allo-threoninato)copper(II): Quantum Chemical Study

“…The nonrelativistic effective-core potentials (ECPs) of Hay and Wadt (LanL2DZ) were used to describe the shielding effects of electrons in copper inner shells. − This basis set will be named BS0 in the following. The choice of this combination of density functional and basis set was based on previous studies of anhydrous and aqua Cu­(aa) 2 complexes, in which the DFT/B3LYP results were verified against experimental X-ray crystal and molecular structures. ,, Besides, the energetics calculated by B3LYP/BS0 for the stationary points of bis­(glycinato)­copper­(II) (Cu­(Gly) 2 ) matched well with the corresponding energy values obtained with G3 calculations at the MP2 level …”

“…Knowledge of isolated complex conformers is a prerequisite to examine and rationalize the influence of intermolecular interactions on the overall complex geometry and the coordination modes in the crystal lattice and aqueous solutions. Another motivation was to do a follow-up study of our previous work on physiological bis­( l- histidinato)­copper­(II), which examined the relative stability of all possible copper­(II) coordination modes and conformations of that complex in the gas phase, and several conformers surrounded with 2, 8, 10, 20, and 22 water molecules by DFT/B3LYP calculations . We concluded that the intermolecular interactions and the arrangement of water molecules around the complex might affect different coordination mode formation .…”

“…Another motivation was to do a follow-up study of our previous work on physiological bis­( l- histidinato)­copper­(II), which examined the relative stability of all possible copper­(II) coordination modes and conformations of that complex in the gas phase, and several conformers surrounded with 2, 8, 10, 20, and 22 water molecules by DFT/B3LYP calculations . We concluded that the intermolecular interactions and the arrangement of water molecules around the complex might affect different coordination mode formation . This paper examines how the stereochemical difference between l -Thr and l - a Thr affects the Cu­( l -Thr) 2 and Cu­( l - a Thr) 2 systems in the gas phase and in aqueous solution, their coordination modes, and the relative stabilities of their possible conformations.…”

Self-Assembled Binuclear Cu(II)–Histidine Complex for Absolute Configuration and Enantiomeric Excess Determination of Naproxen by Tandem Mass Spectrometry

“…Generally, solvent of 50:50 water/methanol (0.1% formic acid) was crucial for the detection of protonated complexes and potassium adduct complexes. Among the chiral selectors investigated, the copper-bound diastereomers [Cu­(II)­(naproxen)­(His)−H] + ( 12 ) and [(Cu­(II)) 2 (naproxen)­(His) 2 −3H] + ( 13 ) (Figure S1) were observed only with His as the chiral selector, which was likely because of the coordination site provided by the imidazole ring in the side chain of histidine in addition to its amino and carboxylic groups. , …”

“…Among the chiral selectors investigated, the copper-bound diastereomers [Cu(II)-(naproxen)(His)−H] + (12) and [(Cu(II)) 2 (naproxen)-(His) 2 −3H] + (13) (Figure S1) were observed only with His as the chiral selector, which was likely because of the coordination site provided by the imidazole ring in the side chain of histidine in addition to its amino and carboxylic groups. 45,46 Figure S2 shows the CID spectra of some typical naproxencontaining diastereomeric complex ions, including (a) [naprox-en+2γ-CD+2H] + ( 2 (15). For all except the copper-containing complexes, loss of naproxen was observed.…”