Ab initio studies on amides: conformational preferences of formimide and barriers to interconversion of the conformers

Formimide (diformamide), the parent of the diacylamines, is capable of existing in three basic ground-state conformations about the N-C bonds. Full geometry optimization with the STO-3G basis set predicts that all three conformers are fully coplanar, that the E,E (1) and E,Z(3) conformers are of similar energy, and that the Z,Z (2) conformer is of somewhat higher energy (by 11 kJ mol-1); 4-31G evaluation of the energies suggests that (2) is by far the least stable and that (1) is of higher energy than (3) by 6.5 kJ mol-1. Analysis of the calculated charge distribution suggests that (2) is destabilized by electrostatic repulsion. These results are consistent with experimental conclusions that planar (3) is strongly preferred in the vapour state at room temperature and that (2) has not been observed in the vapour state or in solution. Partial geometry optimization with the STO-3G basis set of model transition states for internal rotation suggests a barrier height of 52 kJ mol-1 (72 kJ mol-1 when evaluated with the 4-31G basis set) for the conversion (3) → (1).

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Distinctive Supramolecular Features of β-Cyclodextrin Inclusion Complexes with Antidepressants Protriptyline and Maprotiline: A Comprehensive Structural Investigation

Pharmaceuticals ◽

10.3390/ph14080812 ◽

2021 ◽

Vol 14 (8) ◽

pp. 812

Author(s):

Thammarat Aree

Keyword(s):

Inclusion Complexes ◽

Density Functional ◽

Water Solubility ◽

Geometry Optimization ◽

Binding Constants ◽

Basis Set ◽

Full Geometry Optimization ◽

Basis Set Superposition Error ◽

X Ray ◽

Molecular Stability

Depression, a global mental illness, is worsened due to the coronavirus disease 2019 (COVID-2019) pandemic. Tricyclic antidepressants (TCAs) are efficacious for the treatment of depression, even though they have more side effects. Cyclodextrins (CDs) are powerful encapsulating agents for improving molecular stability, water solubility, and lessening the undesired effects of drugs. Because the atomic-level understanding of the β-CD–TCA inclusion complexes remains elusive, we carried out a comprehensive structural study via single-crystal X-ray diffraction and density functional theory (DFT) full-geometry optimization. Here, we focus on two complexes lining on the opposite side of the β-CD–TCA stability spectrum based on binding constants (Kas) in solution, β-CD–protriptyline (PRT) 1—most stable and β-CD–maprotiline (MPL) and 2—least stable. X-ray crystallography unveiled that in the β-CD cavity, the PRT B-ring and MPL A-ring are aligned at a nearly perfect right angle against the O4 plane and primarily maintained in position by intermolecular C–H···π interactions. The increased rigidity of the tricyclic cores is arising from the PRT -CH=CH- bridge widens, and the MPL -CH2–CH2- flexure narrows the butterfly angles, facilitating the deepest and shallower insertions of PRT B-ring (1) and MPL A-ring (2) in the distorted round β-CD cavity for better complexation. This is indicated by the DFT-derived complex stabilization energies (ΔEstbs), although the complex stability orders based on Kas and ΔEstbs are different. The dispersion and the basis set superposition error (BSSE) corrections were considered to improve the DFT results. Plus, the distinctive 3D arrangements of 1 and 2 are discussed. This work provides the first crystallographic evidence of PRT and MPL stabilized in the β-CD cavity, suggesting the potential application of CDs for efficient drug delivery.

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Ab initio studies on amides: conformational preferences of diacetamide and barriers to interconversion of the conformers

Australian Journal of Chemistry ◽

10.1071/ch9802337 ◽

1980 ◽

Vol 33 (11) ◽

pp. 2337 ◽

Cited By ~ 9

Author(s):

L Radom ◽

NV Riggs

Keyword(s):

Hydrogen Atom ◽

Ab Initio ◽

Internal Rotation ◽

Model Systems ◽

Methyl Groups ◽

Electrostatic Repulsion ◽

Conformational Preferences ◽

Out Of Plane ◽

Model Transition ◽

Good Agreement

Diacetamide, like other diacylamines, is capable of existing in three basic conformations about the N-C bonds. Optimization (STO-3G) of model systems in which all first-row atoms and the amido hydrogen atom are held coplanar predicts that the E,Z conformer (3) is of lowest energy, the Z,Z conformer (2) of somewhat higher energy (4.2 kJ mol-1), and the E,E conformer (1) of highest energy (23.6 kJ mol-1); 4-31G evaluation of the energies suggests that (1) and (2) are each of higher energy than (3) by 27-28 kJ mol-1. It is suggested that (2) is destabilized with respect to (3) by electrostatic repulsion of the two negatively charged oxygen atoms whereas destabilization of (1) is due to substantial methyl-methyl steric interactions as reflected in the very wide <CNC (136°); the energy of (1) is, however, raised by out-of-plane or rotational movements of the methyl groups, i.e., the preferred structure (excluding methyl hydrogens) is planar. The calculated height of the barrier to internal rotation of (3) by either of two model transition states is 41-45 kJ mol-1, in good agreement with an experimental value of 45.2 kJ mol-1 in solution at -60°.

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Saddle-point geometries and barriers to internal rotation of formamide : an ab initio study

Australian Journal of Chemistry ◽

10.1071/ch9800249 ◽

1980 ◽

Vol 33 (2) ◽

pp. 249 ◽

Cited By ~ 29

Author(s):

L Radom ◽

NV Riggs

Keyword(s):

Transition State ◽

Ground State ◽

Energy Surface ◽

Saddle Points ◽

Geometry Optimization ◽

Internal Motion ◽

Basis Set ◽

Minimal Basis ◽

Experimental Values ◽

Extended Basis

By use of a direct transition-state program and the STO-3G minimal basis set, two saddle-points are detected on the energy surface for internal motion of formamide. These correspond mainly to rotation about the C-N bond along with some lengthening of this bond and increased pyramidal distortion at nitrogen as compared with that in the ground state. The STO-3G estimates of the barrier height (34-39 kJ mol-1) are in very poor agreement with experimental values (70-90 kJ mol-1), but 4- 31G energy evaluations for the STO-3G-optimized structures give much better estimates (62-80 kJ mol-1). Contrary to a previous report, use of the 4-31G extended basis set for geometry optimization suggests that only the lower-energy member (NH2 cis to CO) of the above pair is a true transition state for internal motion of formamide; its energy relative to that of the 4-31G-optimized ground state (planar) is 83.5 kJ mol-1, very close to the midpoint of the experimental range. The transition state appears to lie in a region of the 4-31G energy surface that is relatively flat with respect to pyramidal distortion at nitrogen; constraining the amino group to planarity raises the calculated energy by only 6.5kJmol-1.

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A CASSCF/CASPT2 STUDY ON THE LOW-LYING ELECTRONIC STATES OF THE (CH3)2CHS AND ITS CATION

Journal of Theoretical and Computational Chemistry ◽

10.1142/s0219633613500478 ◽

2013 ◽

Vol 12 (06) ◽

pp. 1350047

Author(s):

FAN-XIA WANG ◽

ZENG-XIA ZHAO ◽

HONG-XING ZHANG

Keyword(s):

Ground State ◽

Spectroscopic Data ◽

Geometry Optimization ◽

Electronic States ◽

Vibrational Frequencies ◽

Geometric Parameters ◽

Basis Set ◽

Natural Orbital ◽

Atomic Natural Orbital ◽

Good Agreement

The multireference approach (CASSCF/CASPT2) combined with the contracted with atomic natural orbital (ANO-RCC-VTZP) basis set has been used to investigate systematically, the low-lying electronic states of ( CH 3)2 CHS in Cs symmetry. The result of geometry optimization using CASSCF/ANO-RCC-VTZP shows that the theoretically determined geometric parameters and harmonic vibrational frequencies for the ground state X2A′ of ( CH 3)2 CHS are in good agreement with previous studies. In addition, we also explored several cationic states adiabatically and found that the 11A′ state of ( CH 3)2 CHS + is unstable and converts to ( CH 3)2 CSH +. The vertical and adiabatic ionization energies were obtained to compare with photoelectron spectroscopic data.

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Microwave Assisted Synthesis, Antifungal Activity, and DFT Study of Some Novel Triazolinone Derivatives

BioMed Research International ◽

10.1155/2015/916059 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7

Author(s):

Na-Bo Sun ◽

Jian-Zhong Jin ◽

Fang-Yue He

Keyword(s):

Antifungal Activity ◽

Geometry Optimization ◽

Pythium Ultimum ◽

Basis Set ◽

Orbital Energy ◽

Microwave Assisted Synthesis ◽

Good Activity ◽

Full Geometry Optimization ◽

H Nmr ◽

Multistep Reaction

A series of some novel 1,2,4-triazol-5(4H)-one derivatives were designed and synthesized under microwave irradiation via multistep reaction. The structures of 1,2,4-triazoles were confirmed by1H NMR, MS, FTIR, and elemental analysis. The antifungal activities of 1,2,4-triazoles were determined. The antifungal activity results indicated that the compounds5c,5f, and5hexhibited good activity againstPythium ultimum, and the compounds5band5cdisplayed good activity againstCorynespora cassiicola. Theoretical calculation of the compound5cwas carried out with B3LYP/6-31G (d). The full geometry optimization was carried out using 6-31G(d) basis set, and the frontier orbital energy and electrostatic potential were discussed, and the structure-activity relationship was also studied.

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Ab initio studies on amides: triformamide

Australian Journal of Chemistry ◽

10.1071/ch9810007 ◽

1981 ◽

Vol 34 (1) ◽

pp. 7

Author(s):

L Radom ◽

NV Riggs

Keyword(s):

Double Bond ◽

Transition State ◽

Ab Initio ◽

Internal Rotation ◽

Direct Observation ◽

Ground State ◽

Basis Set ◽

Model Transition ◽

Bond Character ◽

Complete Optimization

Complete optimization with the STO-3G basis set of the geometries of the planar ground-state conformers of the (unknown) triformamide molecule predicts that the E,E,E conformer will be more stable than the E,Z,Z conformer by 12.6 kJ mol-1 (or 42.3 kJ mol-1 by energy evaluations with the 4-31G basis set). These differences make direct observation of the E,Z,Z-conformer unlikely. Corresponding optimization of a model transition state for the conversion of the E,Z,Z into the E,E,E conformer suggests that the barrier to internal rotation is low with a calculated height of 33 kJ mol-1 (24 kJ mol-1 when evaluated with the 4-31G basis set). Successive formyl substitution in ammonia, represented by the series of molecules formamide, diformamide (formimide) and triformamide, leads to decreasing double-bond character in the N-C bonds as reflected in increasing N-C bond lengths, decreasing Mulliken π-overlap populations and decreasing barriers to rotation. Extension of the results for these three molecules suggests that the (known) triacetamide molecule has a non-planar E,E,E-type structure as is consistent with the observation of a single signal in its 1H n.m.r. spectrum.

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Synthesis, Crystal Structure, and Theoretical Studies of N-(4-((4-chlorobenzyl)oxy)phenyl)-4- (trifluoromethyl)pyrimidin-2-amine

Journal of Chemistry ◽

10.1155/2013/521757 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Jian-Chang Jin ◽

Zhao-Hui Sun ◽

Ming-Yan Yang ◽

Jing Wu ◽

Xing-Hai Liu

Keyword(s):

Title Compound ◽

Geometry Optimization ◽

Basis Set ◽

Orbital Energy ◽

Monoclinic Space Group ◽

X Ray Diffraction ◽

Full Geometry Optimization ◽

X Ray ◽

Compound C ◽

Frontier Orbital Energy

The title compound (C18H13ClF3N3O) were synthesized and recrystallized from CH3OH. The compound was characterized byH1NMR, MS, HRMS, and X-ray diffraction. The compound crystallized in the monoclinic space groupP2(1)/nwitha=8.2354(14),b=12.686(2),c=16.633(3) Å,α=90,β=97.951(3),γ=90∘,V=1721.0(5) Å3,Z=4,andR=0.0376for 1933 observed reflections withI>2σ(I).X-ray analysis reveals that intermolecular N–H⋯N interactions exist in the adjacent molecules. Theoretical calculation of the title compound was carried out with HF/6-31G(d,p), B3LYP/6-31G(d,p). The full geometry optimization was carried out using 6-31G(d,p)basis set and the frontier orbital energy. The optimized geometric bond lengths and bond angles obtained by using HF and DFT (B3LYP) showed the best agreement with the experimental data.

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Room-Temperature Chemical Synthesis of C2

10.26434/chemrxiv.8009633 ◽

2019 ◽

Author(s):

Kazunori Miyamoto ◽

Shodai Narita ◽

Yui Masumoto ◽

Takahiro Hashishin ◽

Mutsumi Kimura ◽

...

Keyword(s):

Chemical Synthesis ◽

Ground State ◽

Room Temperature ◽

Chemical Species ◽

Quadruple Bond ◽

Photon Excitation ◽

Physical Energy ◽

Theoretical Predictions ◽

Carbon Arc ◽

Inherent Nature

Diatomic carbon (C2) is historically an elusive chemical species. It has long been believed that the generation of C2 requires extremely high “physical” energy, such as an electric carbon arc or multiple photon excitation, and so it has been the general consensus that the inherent nature of C2 in the ground state is experimentally inaccessible. Here, we present the first “chemical” synthesis of C2 in a flask at room temperature or below, providing the first experimental evidence to support theoretical predictions that (1) C2 has a singlet biradical character with a quadruple bond, thus settling a long-standing controversy between experimental and theoretical chemists, and that (2) C2 serves as a molecular element in the formation of sp2-carbon allotropes such as graphite, carbon nanotubes and C60.

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ß-Cyclodextrin Inclusion Complexes with Catechol-Containing Antioxidants Protocatechuic Aldehyde and Protocatechuic Acid—An Atomistic Perspective on Structural and Thermodynamic Stabilities

Molecules ◽

10.3390/molecules26123574 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3574

Author(s):

Thammarat Aree

Keyword(s):

Inclusion Complexes ◽

Protocatechuic Acid ◽

Inclusion Complexation ◽

Geometry Optimization ◽

Therapeutic Effects ◽

Full Geometry Optimization ◽

Oh Groups ◽

X Ray ◽

Protocatechuic Aldehyde ◽

Crystal Contacts

Protocatechuic aldehyde (PCAL) and protocatechuic acid (PCAC) are catechol derivatives and have broad therapeutic effects associated with their antiradical activity. Their pharmacological and physicochemical properties have been improved via the cyclodextrin (CD) encapsulation. Because the characteristics of b-CD inclusion complexes with PCAL (1) and PCAC (2) are still equivocal, we get to the bottom of the inclusion complexation by an integrated study of single-crystal X-ray diffraction and DFT full-geometry optimization. X-ray analysis unveiled that PCAL and PCAC are nearly totally shielded in the b-CD wall. Their aromatic rings are vertically aligned in the b-CD cavity such that the functional groups on the opposite side of the ring (3,4-di(OH) and 1-CHO/1-COOH groups) are placed nearby the O6–H and O2–H/O3–H rims, respectively. The preferred inclusion modes in 1 and 2 help to establish crystal contacts of OH×××O H-bonds with the adjacent b-CD OH groups and water molecules. By contrast, the DFT-optimized structures of both complexes in the gas phase are thermodynamically stable via the four newly formed host–guest OH⋯O H-bonds. The intermolecular OH×××O H-bonds between PCAL/PCAC 3,4-di(OH) and b-CD O6–H groups, and the shielding of OH groups in the b-CD wall help to stabilize these antioxidants in the b-CD cavity, as observed in our earlier studies. Moreover, PCAL and PCAC in distinct lattice environments are compared for insights into their structural flexibility.

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