Effects of charging and polarization on molecular conduction via the source-sink potential method

N-Methylation has a significant impact on improving the oral bioavailability, lipophilicity and aqueous solubility of peptide-based lead drug structures. The selected mono-amino acid derivatives Ac-X-OMe, where X = Gly, Val, Leu, Ile, Phe, Met, Cys, Ser, Asp and His as well as their corresponding N-methylated analogues were studied. The clog P values of all N-methylated peptides are greater than those of native compounds. Quantum chemical calculations were performed to estimate the aqueous solubility of these lipophilic compounds using density functional theory (DFT). To confirm the contribution of dispersion forces on quantum chemical data, the long-range corrected (LC) hybrid density functional (ωB97X-D) was also probed for some amino acid derivatives. The ωB97X functional gave similar results. Our results reveal that after mono N-methylation of the peptide backbone, ΔGsolv becomes more negative (more water soluble) while polarizability and dipole moment are also increased. Natural atomic charges derived by natural bond orbital (NBO) analysis of N, C, and O atoms involved in amide functional group become more positive/(less negative) after N-methylation. All N-methylated amino acids have higher EHOMO (less negative) in comparison with the amino acid analogues, and in all cases N-methylation decreases EHOMO-LUMO. The calculated amide cis/trans activation energies (EA) of all the N-methylated amino acid derivatives were lower than that of native species. N-methylation of these compounds leads to an increase in lipophilicity, aqueous solubility, polarization, dipole moment and lowering of the cis/trans amide energy barrier (EA).

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“…[94,95] The latter is therefore also linked to solubility. [94,95] The latter is therefore also linked to solubility.…”

Section: Frontier Molecular Orbitals (Homo Lumo)mentioning

confidence: 99%

“…93 Frontier molecular orbitals (HOMO, LUMO) Molecular polarizability and atomic electron densities/charges are directly linked to the frontier molecular orbitals. 94,95 The latter is therefore also linked to solubility. [96][97][98][99] E HOMO describes the tendency of the molecule to donate electrons (charge density).…”

Section: Analysis Of Atomic Chargesmentioning

confidence: 99%

The effect of N-methylation of amino acids (Ac-X-OMe) on solubility and conformation: a DFT study

et al. 2015

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“…HOMO and LUMO are also regarded as the frontier molecular orbitals . The electron‐donating ability of a complex is associated with the E HOMO ; the higher the E HOMO energies (less negative), the more energy, implying more ability to donate electrons .…”

Section: Dft Analysismentioning

confidence: 99%

Novel 3‐Hydroxy‐2‐naphthoic hydrazone and Ni(II), Co(II) and Cu(II) Complexes: Synthesis, Spectroscopic Characterization, Antimicrobial, DNA Cleavage and Computational Studies

Ekennia

Ibezim

Okpareke

et al. 2019

Applied Organom Chemis

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A novel hydrazone ligand derived from condensation reaction of 3-hydroxy-2naphthoic hydrazide with dehydroacetic acid, and its Ni(II), Cu(II) and Co(II) complexes were synthesized, characterized by spectroscopic, elemental analyses, magnetic susceptibility and conductivity methods, and screened for antimicrobial, DNA binding and cleavage properties. Spectroscopic analysis and elemental analyses indicated the formula, [MLCl 2 ], for the complexes; square planar geometry for the nickel, and tetrahedral geometry for copper and cobalt complexes. The non-electrolytic natures of the complexes in Dimethyl Sulphoxide (DMSO) were confirmed by their molar conductance values in the range of 6.11-14.01 Ω −1 cm 2 mol −1 . The copper complex had the best antibacterial activity against Staphylococcus aureus (ATCC 29213). DNA cleavage activities of the compounds, evaluated on pBR322 DNA, by agarose gel electrophoresis, in the presence and absence of oxidant (H 2 O 2 ) and free radical scavenger (DMSO), indicated no activity for the ligand, and moderate activity for the complexes, with the copper complex cleaving pBR322 DNA more efficiently in the presence of H 2 O 2 . When the complexes were evaluated for antibacterial and A-DNA activity using Molecular docking technique, the copper complex was found to be most effective against Gram-positive (S. aureus) bacteria. [CuLCl 2 ] showed good hydrogen bonding interaction with the major-groove (C 2 . G 13 base pair) of A-DNA. Density functional theory (DFT) calculations of the structural and electronic properties of the complexes revealed that [CuLCl 2 ] had a smaller HOMO-LUMO gap, suggesting a higher tendency to donate electrons to electron-accepting species of biological targets.

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“…Readers who want to know the rigorous definition of the complex counter energy can see the Appendix. The counter quasi-particle energy can also be realized by the source-sink complex potential 39,40,56 proposed by Goyer et al in studying the open systems. The perturbation is given byV =L 0 −L =V int +V ct , which includes the quasi-particle interactionsV int and the counter-termV ct .…”

Section: A Renormalized Perturbation Theorymentioning

confidence: 99%

“…Several theoretical methods have been proposed to study the charge transport through molecular junctions in the presence of electron-electron interaction and beyond the single-site model, such as Landauer's formula with meanfield approximation, [18][19][20] nonequilibrium Green's function (NEGF) with GW approximation, 21-23 many-body perturbation theory, 24, 25 equation of motion method, [26][27][28][29][30] master equation, [31][32][33] quantum master equation, 34,35 hierarchical equations of motion approach, 36,37 renormalized perturbation theory, 38 source-sink potential formalism, 39,40 and dynamical mean-field theory. 41 However, most methods are useful either for the Coulomb blockade regime, where the electronelectron interaction dominates, or the coherent tunneling regime, where the molecule-lead interaction dominates.…”

Section: Introductionmentioning

confidence: 99%

Theory of charge transport in molecular junctions: From Coulomb blockade to coherent tunneling

Chang

Jin

2014

The Journal of Chemical Physics

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We study charge transport through molecular junctions in the presence of electron-electron interaction using the nonequilibrium Green's function techniques and the renormalized perturbation theory. In the perturbation treatment, the zeroth-order Hamiltonian of the molecular junction is composed of independent single-impurity Anderson's models, which act as the channels where charges come through or occupy, and the interactions between different channels are treated as the perturbation. Using this scheme, the effects of molecule-lead, electron-electron, and hopping interactions are included nonperturbatively, and the charge transport processes can thus be studied in the intermediate parameter range from the Coulomb blockade to the coherent tunneling regimes. The concept of quasi-particles is introduced to describe the kinetic process of charge transport, and then the electric current can be studied and calculated. As a test study, the Hubbard model is used as the molecular Hamiltonian to simulate dimeric and trimeric molecular junctions. Various nonlinear current-voltage characteristics, including Coulomb blockade, negative differential resistance, rectification, and current hysteresis, are shown in the calculations, and the mechanisms are elucidated.

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Effects of charging and polarization on molecular conduction via the source-sink potential method

Cited by 9 publications

References 27 publications

The effect of N-methylation of amino acids (Ac-X-OMe) on solubility and conformation: a DFT study

The effect of N-methylation of amino acids (Ac-X-OMe) on solubility and conformation: a DFT study

Novel 3‐Hydroxy‐2‐naphthoic hydrazone and Ni(II), Co(II) and Cu(II) Complexes: Synthesis, Spectroscopic Characterization, Antimicrobial, DNA Cleavage and Computational Studies

Theory of charge transport in molecular junctions: From Coulomb blockade to coherent tunneling

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