The influence of substituent field and resonance effects on the ease of N-heterocyclic carbene formation from imidazolium rings

Using a set of twelve selected substituents, the influence of substituent properties on the ease of deprotonation of imidazolium cations and mesoionic imidazolium-4-olates measured by the CREF index has been investigated. Significant correlations between CREF values and the Swain and Lupton field (F) and resonance (R) substituent constants have been found. In all cases the field effect has the greatest influence but resonance effects are also significant

DFT Study of 1,4-Diazonium-3,6-diolates: Monocyclic Representatives of Unexplored Semi-Conjugated Heterocyclic Mesomeric Betaines

Compared to the well-known conjugated (1,3-dipolar) and cross-conjugated (1,4-dipolar) heterocyclic mesomeric betaines (HMBs), semi-conjugated HMBs are unexplored and almost unknown. The three discrete classes of HMB are defined by the connectivity between their ring 2π heteroatoms and the odd-conjugated fragments that complete the ring. A single example of a stable, fully-characterized semi-conjugate HMB has been reported. This study employs the density functional theory (DFT) methodology to investigate the properties of a series of six-membered semi-conjugated HMBs. The electronic character of ring substituents is found to significantly influence the structure and electronic properties of the ring. The aromaticity measured by HOMA and NICS(1)zz indices is increased by π-electron-donating substituents whereas π-electron-withdrawing substituents decrease the calculated aromatic character and ultimately lead to non-planar boat or chair structures. A notable property of all derivatives is the small energy gap between their frontier orbitals

Natural bond orbital approach to the transmission of substituent effect through the fulvene and benzene ring systems

International audienceElectronic structure of 22 monosubstituted derivatives of benzene and exocyclically substituted fulvene with substituents: B(OH), BH, CCH, CF, CH, CHCH, CHO, Cl, CMe, CN, COCH, CONH, COOH, F, NH, NMe, NO, NO, OCH, OH, SiH, SiMe were studied theoretically by means of Natural Bond Orbital analysis. It is shown, that sum of π-electron population of carbon atoms of the fulvene and benzene rings, and respectively correlate well with Hammett substituent constants and aromaticity index NICS. The substituent effect acting on pi-electron occupation at carbon atoms of the fulvene ring is significantly stronger than in the case of benzene. Electron occupations of ring carbon atoms (except C1) in fulvene plotted against each other give linear regressions with high correlation coefficients. The same is true for and carbon atoms in benzene. Positive slopes of the regressions indicate similar for fulvene and benzene kind of substituent effect - mostly resonance in nature. Only the regressions of occupation at the carbon atom in position of benzene against and positions gives negative slopes and low correlation coefficients

A Quantitative Analysis of Factors Influencing Ease of Formation and σ‑Bonding Strength of Oxa- and Thia-N-Heterocyclic Carbenes

The index described previously (carbene relative energy of formation) has been extended to oxygen and sulfur heterocycles. This provides a quantitative overview of factors determining ease of formation of (i) neutral N-heterocyclic carbenes (NHCs) by deprotonation of heterocyclic salts and (ii) anionic NHCs by deprotonation of heterocyclic mesomeric betaines. The influence of the nature and ring position of oxygen and sulfur is discussed for a range of known and unknown systems. Attention is directed to unexplored systems of potential interest

Sigma- and pi- electron structure of aza-azoles

International audienceThe reasons behind changes of aromaticity in 10 unsubstituted aza-azoles were analysed by employing the natural bond orbital (NBO) approach at the MP2/6-311+G(d,p) level of theory. Sum of occupations of orbitals at atoms in the ring correlates well with the magnetism based aromaticity index NICS as well as with the number of nitrogen atoms in the ring. Changes of NICS depend strongly in a linear way on the number of NN bonds. Classification of azoles based on the number of pyridine-type nitrogen atoms vicinal to NH is supported by plotting the relative occupation of π orbitals (π) against the relative occupation of σ orbitals (σ) for all individual atoms in rings

A DFT study of mono-, bi- and tricyclic examples ofsemi-conjugated heterocyclic mesomeric betaines

The properties of heterocyclic mesomeric betaines (HMBs) are determined by the connectivity between the ring 2π heteroatoms and the odd conjugated fragments that complete the ring. In contrast to conjugated HMBs (1,3-dipoles) and cross-conjugated HMBs (1,4-dipoles), semi-conjugated HMBs are a class of heterocycle that is unexplored. The only known example is 1,4-dimethyl-1,2,4,5-tetrazinium-3,6-diolate. In this study density functional theory (DFT) methodology is employed to further investigate the structures and properties of examples of mono- bi- and tricyclic semi-conjugated HMBs. A common feature associated with the ‘semiconjugation’ is a small energy gap between the frontier orbitals

Thermodynamic and Kinetic Characteristics of Molnupiravir Tautomers and Its Complexes with RNA Purine Bases as an Explanation of the Possible Mechanism of Action of This Novel Antiviral Medicine: A Quantum-Chemical Study

The mechanism of action of molnupiravir, a novel antiviral drug, was analyzed from the point of view of its tautomerism by means of quantum-mechanical calculations. It was established that although the uracil-like tautomer Mu (3 kcal/mol in the water environment) is the most thermodynamically stable, in fact, it is the cytosine-like tautomer Mc that plays the main role. There are several reasons, as follows: (1) A large part of Mu exists as a more stable but inactive form Mu-m that is unable to pair with adenine. (2) The phosphorylated form of Mc is only 1 kcal/mol less stable than Mu in the water environment and thus is readily available for building into the RNA strand, where the Mu/Mc energy gap increases and the probability of Mc → Mu interconversion leading to C → U mutation is high. (3) The guanine-Mc complex has similar stability to guanine-cytosine, but the adenine-Mu complex has lower stability than adenine-uracil. Additionally, the guanine-Mc complex has a suboptimal distorted geometry that further facilitates the mutations. (4) The activation barrier for proton transfer leading to Mu-m interconversion into a cytosine-like tautomer is higher than for Mu, which makes the uracil-like form even less available. These facts confirm an intriguing experimental observation that molnupiravir competes mainly with cytosine and not uracil