Computational methods for conformational analysis of unsymmetrical 1,3-diamines: 3-aminotropanes

Lewin, Anita H.; Sorensen, Jennifer B.; Dustman, John A.; Bowen, J. Phillip

doi:10.1002/(sici)1096-987x(199910)20:13<1371::aid-jcc4>3.0.co;2-r

Cited by 3 publications

(1 citation statement)

References 2 publications

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“…18 ). Thus, the conformational preferences [ 298 ] of this molecule are determined by the steric interactions between coaxial N-Me group and C-H ax bonds in the six-membered ring (Fig. 18 , structure 1c ) or in the five-membered ring (Fig.…”

Section: Resultsmentioning

confidence: 99%

Conformational energies of reference organic molecules: benchmarking of common efficient computational methods against coupled cluster theory

Stylianakis,

Zervos,

Lii

et al. 2023

J Comput Aided Mol Des

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We selected 145 reference organic molecules that include model fragments used in computer-aided drug design. We calculated 158 conformational energies and barriers using force fields, with wide applicability in commercial and free softwares and extensive application on the calculation of conformational energies of organic molecules, e.g. the UFF and DREIDING force fields, the Allinger’s force fields MM3-96, MM3-00, MM4-8, the MM2-91 clones MMX and MM+, the MMFF94 force field, MM4, ab initio Hartree–Fock (HF) theory with different basis sets, the standard density functional theory B3LYP, the second-order post-HF MP2 theory and the Domain-based Local Pair Natural Orbital Coupled Cluster DLPNO-CCSD(T) theory, with the latter used for accurate reference values. The data set of the organic molecules includes hydrocarbons, haloalkanes, conjugated compounds, and oxygen-, nitrogen-, phosphorus- and sulphur-containing compounds. We reviewed in detail the conformational aspects of these model organic molecules providing the current understanding of the steric and electronic factors that determine the stability of low energy conformers and the literature including previous experimental observations and calculated findings. While progress on the computer hardware allows the calculations of thousands of conformations for later use in drug design projects, this study is an update from previous classical studies that used, as reference values, experimental ones using a variety of methods and different environments. The lowest mean error against the DLPNO-CCSD(T) reference was calculated for MP2 (0.35 kcal mol−1), followed by B3LYP (0.69 kcal mol−1) and the HF theories (0.81–1.0 kcal mol−1). As regards the force fields, the lowest errors were observed for the Allinger’s force fields MM3-00 (1.28 kcal mol−1), ΜΜ3-96 (1.40 kcal mol−1) and the Halgren’s MMFF94 force field (1.30 kcal mol−1) and then for the MM2-91 clones MMX (1.77 kcal mol−1) and MM+ (2.01 kcal mol−1) and MM4 (2.05 kcal mol−1). The DREIDING (3.63 kcal mol−1) and UFF (3.77 kcal mol−1) force fields have the lowest performance. These model organic molecules we used are often present as fragments in drug-like molecules. The values calculated using DLPNO-CCSD(T) make up a valuable data set for further comparisons and for improved force field parameterization. Graphical abstract

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Section: Resultsmentioning

confidence: 99%

Conformational energies of reference organic molecules: benchmarking of common efficient computational methods against coupled cluster theory

Stylianakis,

Zervos,

Lii

et al. 2023

J Comput Aided Mol Des

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An ab initio study of the electrostatics of protonated amines: application to the molecular mechanics (MM3) force field

Sorensen

Lewin

Bowen

2003

Journal of Molecular Structure: THEOCHEM

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Ab Initio and Molecular Mechanics (MM3) Calculations of Protonated−Neutral Diamine Hydrogen Bonds

2001

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Ab initio calculations of cation-neutral diamine complexes have been carried out at the MP2/6-311+G** level. The geometry and energetics of the charge-reinforced hydrogen bond are analyzed with respect to the alkyl substitution of both the protonated and neutral nitrogen atoms, and these results have been used to improve the quality of the MM3(2000) force field. In addition, specialized hydrogen bond parameters optimized for MM3(2000) are presented. These parameters allow very accurate gas-phase modeling of the charge-neutral diamine environment. Molecular mechanics calculations can model effectively protonated amine-neutral amine hydrogen bonds in the gas phase and solution (continuum dielectric) through a combination of charge-dipole interactions and explicit hydrogen-bonding terms.

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Computational methods for conformational analysis of unsymmetrical 1,3-diamines: 3-aminotropanes

Cited by 3 publications

References 2 publications

Conformational energies of reference organic molecules: benchmarking of common efficient computational methods against coupled cluster theory

Conformational energies of reference organic molecules: benchmarking of common efficient computational methods against coupled cluster theory

An ab initio study of the electrostatics of protonated amines: application to the molecular mechanics (MM3) force field

Ab Initio and Molecular Mechanics (MM3) Calculations of Protonated−Neutral Diamine Hydrogen Bonds

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