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An efficient method for the conversion of biphenyl acrylamides to dibenzoazepinones with −SCF3 incorporation is described. This operationally simple radical cascade reaction employs CAN as an oxidant and exhibits good functional group tolerance. Substrates featuring −OCH3, −CH3, −Br or −Cl at the para‐position of the aromatic ring exhibits a preference for an ipso‐cyclization due to the intervention of DMSO in the reaction. Density functional theory (DFT) calculations provide valuable insights into the reaction's energetics and product selectivity. [ABSTRACT FROM AUTHOR]

A theoretical investigation on the cooperativity of a series of binary, ternary, and quaternary complexes interconnected by pnicogen bonds has been conducted using calculations at the M06‐2X/aug‐cc‐pVTZ level of density functional theory. By measuring changes in the molecular electrostatic potential (MESP) at the nucleus of interacting atoms in all of the complexes, it is possible to quantify the substantial reorganization of the electron density triggered by the formation of pnicogen bonds. The positive change in MESP, indicating a loss of electron density from the donor molecule in a dimer, facilitates the acceptance of electron density from a third molecule, resulting in the formation of a ternary complex with a stronger pnicogen bond compared to the one present in the binary complex. Similarly, the acceptor molecule in a dimer with a negative change in MESP showed an enhanced tendency to donate electron density to an electron‐deficient third molecule. The MESP analysis provided valuable insights into the donor/acceptor characteristics of pnicogen bonds within the quaternary complexes. The proposed MESP hypotheses are consistent with the positive cooperativity observed in the pnicogen‐bonded clusters. To quantify the changes in MESP, both at the donor atom (ΔVdonor) and the acceptor atom (ΔVacceptor), for all pnicogen bonds in the cluster, the total change in MESP (ΔΔVn) was measured as ΔΔVn = ∑(ΔVdonor)−∑(ΔVacceptor). Remarkably, ΔΔVn exhibited a strong linear relationship with the sum of the bond energies of the pnicogen bonds in the cluster. This establishes the MESP analysis as a robust approach for understanding the strength and cooperative behavior of pnicogen‐bonded clusters. Additionally, the MESP features provided clear evidence of pnicogen bond formation, further supporting the reliability of this approach. [ABSTRACT FROM AUTHOR]

We define Vn as the molecular electrostatic potential (MESP) at the nucleus of a free atom, calculated excluding the contribution of that nucleus charge. The Vn value at the nucleus of a free atom and that within the atom-in-molecule state show substantial difference (ΔVn) due to alterations in the electronic configuration of the atom resulting from molecular bonding. Thus, variations in molecular structure and bonding lead to differing ΔVn values for the same type of atoms in molecules. The Vn analysis focuses on frequently occurring ring structures in drugs and several drug molecules using density functional theory (DFT) at the M06L/6-311++G(d,p) level. The summation of ΔVn for all heteroatoms acting as hydrogen bond acceptors (HBA) yields ΣΔVn(A), while ΣΔVn(H) represents the cumulative sum of ΔVn for hydrogen atoms participating in hydrogen bond donors (HBD) and those in C–H bonds near heteroatoms. The total hydrogen bond propensity of a drug molecule (EHBP) is predicted by EHBP = 0.05 (ΣΔVn(A) − ΣΔVn(H)) − 7.68n. This equation is derived using interaction energy (ΣEint) calculations for 'n' configurations of twenty ring molecule⋯H2O complexes. The EHBP and ΣEint showed a strong linear relationship with R = 0.974. Further, the EHBP equation is validated using the ΣEint data of FDA-approved oral drugs. The EHBP prediction, solely based on MESP data, ranges from −2.3 to −131.5 kcal mol−1 for 193 FDA-approved oral drugs. Most orally administered drugs adhering to Lipinski's rule of five criteria typically fall within the EHBP range of −16.0 to −84.0 kcal mol−1. The study also derived a relationship between EHBP and Lipinski's rule of five (Ro5) parameters by incorporating a new parameter that accounts for hydrogen atoms participating in Ow⋯H interactions from CH groups. This research presents a robust MESP-based approach for predicting hydrogen bond propensity in drug molecules, complementing drug design and optimization efforts. The correlation with Lipinski's rule of five parameters underscores the importance of hydrogen bond interactions in drug-likeness. [ABSTRACT FROM AUTHOR]

Molecular electrostatic potential (MESP) topology analysis reveals the underlying phenomenon of the through-space effect (TSE), which imparts electron donor–acceptor properties to a wide range of chemical systems, including derivatives of pyrrole, indole, isoindole, azulene, and aniline. The TSE is inherent in pyrrole owing to the strong polarization of electron density (PoED) from the formally positively charged N-center to the C3C4 bonding region. The N → C3C4 directional nature of the TSE has been effectively employed to design molecules with high electronic polarization, such as bipyrroles, polypyrroles, phenyl pyrroles, multi-pyrrolyl systems and N-doped nanographenes. In core-expanded structures, the direction of electron flow from pyrrole units towards the core leads to highly electron-rich systems, while the opposite arrangement results in highly electron-deficient systems. Similarly, the MESP analysis reveals the presence of the TSE in azulene, indole, isoindole, and aniline. Oligomeric chains of these systems are designed in such a way that the direction of electron flow is consistent across each monomer, leading to substantial electronic polarization between the first and last monomer units. Notably, these designed systems exhibit strong donor–acceptor characteristics despite the absence of explicit donor and acceptor moieties, which is supported by FMO analysis, APT charge analysis, NMR data and λmax data. Among the systems studied, the TSEs of many experimentally known systems (bipyrroles, phenyl pyrroles, hexapyrrolylbenzene, octapyrrolylnaphthalene, decapyrrolylcorannulene, polyindoles, polyazulenes, etc.) are unraveled for the first time, while numerous new systems (polypyrroles, polyisoindoles, and amino-substituted benzene polymers) are predicted to be promising materials for the creation of donor–acceptor systems. These findings demonstrate the potential of the TSE in molecular design and provide new avenues for creating functional materials. [ABSTRACT FROM AUTHOR]

Molecular electrostatic potential (MESP) analysis is employed to predict the hydrogen bond (HB) interaction strength (Eint) of frequently encountered chemical motifs (CO–HC, CN–HN, CN–HC, CF–HC, and CN–OC) in commonly observed heterocyclic rings in drugs with H2O using the M06L/6-311++G(d,p) level of DFT. The Eint of ring⋯H2O complexes is rationalized in terms of the MESP change observed at the nuclei of heteroatoms, viz. ΔVn(CN), ΔVn(CF) and ΔVn(CO) as well as that at the hydrogen atom, viz. ΔVn(NH) and ΔVn(CH). The ordered pair of (ΔVn of heteroatom, ΔVn of H atom) in the ring molecule showed the (+, +), (+, −), (−, +), and (−, −) variations with respect to a reference molecule. The (−, +) MESP behaviour always strengthened the (ring)heteroatom⋯Hw and Ow⋯H(ring) interactions while the (+, −) behaviour weakened these interactions. Furthermore, the (+, −) and (−, +) behaviours led to mixed Eint responses. Linear regression models based on two ΔVn parameters have been derived, producing solid predictions on even the finest changes in the Eint values of the five categories of ring molecules. The MESP hypotheses led to a profound understanding of the contributions of individual HBs within the realm of bidentate interactions. The ΔVn parameters have emerged as very sensitive electronic properties to understand even the subtle variations in the HB strength of molecular interactions, which offer a priori prediction of HB strength as well as suggest the tunability of HB strength within drug motifs. [ABSTRACT FROM AUTHOR]

The covalent and non-covalent nature of carbon–carbon (CC) interactions in a wide range of molecular systems can be characterized using various methods, including the analysis of molecular electrostatic potential (MESP), represented as V(r), and the molecular electron density (MED), represented as ρ(r). These techniques provide valuable insights into the bonding between carbon atoms in different molecular environments. By uncovering a fundamental exponential relationship between the distance of the CC bond and the highest eigenvalue (λv1) of V(r) at the bond critical point (BCP), this study establishes the continuum model for all types of CC interactions, including transition states. The continuum model is further delineated into three distinct regions, namely covalent, borderline cases, and non-covalent, based on the gradient, , with the bond distance of the CC interaction. For covalent interactions, this parameter exhibits a more negative value than −5.0 a.u. Å−1, while for non-covalent interactions, it is less negative than −1.0 a.u. Å−1. Borderline cases, which encompass transition state structures, fall within the range of −1.0 to −5.0 a.u. Å−1. Furthermore, this study expands upon Popelier's analysis of the Laplacian of the MED, denoted as ∇2ρ, to encompass the entire spectrum of covalent, non-covalent, and borderline cases of CC interactions. Therefore, the present study presents compelling evidence supporting the concept of a continuum model for CC bonds in chemistry. Additionally, this continuum model is further explored within the context of C–N, C–O, C–S, N–N, O–O, and S–S interactions, albeit with a limited dataset. [ABSTRACT FROM AUTHOR]

The OCNH unit is one of the most frequently encountered structural motifs in rings in drugs which serves dual role as the proton donor through NH bond and proton acceptor through the CO bond. Here, we predicted the HB strength (Eint) of OCNH motif with H2O for commonly observed 37 rings in drugs with DFT method M06L/6‐311++G(d,p). The HB strength is rationalized in terms of molecular electrostatic potential (MESP) topology parameters ΔVn(NH) and ΔVn(CO) which describe the relative electron deficient/rich nature of NH and CO, respectively, with respect to the reference formamide. The Eint of formamide is −10.0 kcal/mol whereas the Eint of ring systems is in the range −8.6 to −12.7 kcal/mol—a minor increase/decrease compared to the formamide. The variations in Eint are addressed using the MESP parameters ΔVn(NH) and ΔVn(CO) and proposed the hypothesis that a positive ΔVn(NH) enhances NH...Ow interaction while a negative ΔVn(CO) enhances the CO...Hw interaction. The hypothesis is proved by expressing Eint jointly as ΔVn(NH) and ΔVn(CO) and also verified for twenty FDA approved drugs. The predicted Eint for the drugs using ΔVn(NH) and ΔVn(CO) agreed well with the calculated Eint. The study confirms that even delicate variations in the electronic feature of a molecule can be quantified in terms of MESP parameters and they provide a priori prediction of the HB strength. The MESP topology analysis is recommended to understand the tunability of HB strength in drug motifs. [ABSTRACT FROM AUTHOR]

The structural and electronic properties of several nitrogen-doped fullerenes, C60−2nN2n (n = 1–12), have been studied using density functional theory (DFT) at the M06L/6-311+G(d)//M06L/6-31G(d) level. The electronic features studied using a molecular electrostatic potential (MESP) topology analysis revealed that increasing the N-doping leads to a large improvement in the electron density of the carbon cage. As a result, the N-doped fullerenes showed a stronger interaction with CO2 molecules than C60. Also, the formation of large clusters of CO2 around the N-doped C60 is modeled which revealed that the interaction energy per CO2 is better than the interaction of a single CO2 with the same system. The improved interaction of CO2 in the cluster is attributed to the positive cooperative interaction arising between the adsorbed CO2 molecules. The study also examined the MESP features and the CO2 binding affinity of the anionic modification of the N-doped C60 by attaching a CN− unit on a carbon center. Compared to the N-doped C60, the highly electron-rich anion (C60−2nN2nCN)− showed improved affinity to CO2. The superior electronic features and CO2 binding energy data of N-fullerenes and N-cyanofullerides suggest that they are potent CO2 capturing agents. [ABSTRACT FROM AUTHOR]

The (C60CN)− formed by the reaction of CN− with fullerene shows high electron rich character, very similar to C60˙−, and it behaves as a large anion. Similar to Cp−, the bulky anion, (C60CN)−, acts as a strong η5 ligand towards transition metal centers. Previous studies on η5 coordination of fullerene cage are reported for pseudo fullerenes whereas the present study deals with sandwich complexes of (C60CN)− with Fe(II), Ru(II), Cr(II), Mo(II), and Ni(II) and multi‐decker sandwich complexes of CN–fullerides with Fe(II). The structural parameters of these complexes and the corresponding Cp− complexes showed very close resemblance. Analysis of the metal‐to‐carbon bonding molecular orbitals showed that sandwich complex [Fe(η5‐(C60CN)−)2] exhibit bonding features very similar to that of ferrocene. Also, a 6‐fold decrease in the band gap energy is observed for [Fe(η5‐(C60CN)−)2] compared to ferrocene. The energy of dissociation (ΔE) of the ligand (C60CN)− from [Fe(η5‐(C60CN)−)2] is slightly lower than the ΔE of a Cp* ligand from a ferrocene derivative wherein each cyclopentadienyl unit is substituted with four tertiary butyl groups. The (C60CN)− ligand behaved as one of the bulkiest ligands in the chemistry of sandwich complexes. Further, the coordinating ability of the dianion, (C60(CN)2)2− is evaluated which showed strong coordination ability simultaneously with two metal centers leading to the formation of multi‐decker sandwich and pearl‐necklace type polymeric structures. [ABSTRACT FROM AUTHOR]

The reaction of C60 fullerene with 'n' molecules (n = 1 to 6) of 1,3-dimethyl-2,3-dihydro-2-cyano-imidazole (IMCN) results in the exothermic formation of imidazolium cation-polyanionic fulleride complexes, (IM+)n⋯((C60(CN)n)n−). The binding energy of IM+ with (C60(CN)n)n− in the imidazolium-fulleride ionic complexes increased from −69.6 kcal mol−1 for n = 1 to −202.9 kcal mol−1 for n = 6. The energetics of the complex formation and cation–anion interaction energy data suggest the formation of imidazolium-fulleride ionic liquid (IL) systems. Furthermore, the dimer formation of such ionic complexes showed more exergonic nature due to multiple cooperative electrostatic interactions between oppositely charged species and suggested improved energetics for higher order clusters. The molecular electrostatic potential (MESP) analysis has revealed that the extra 'n' electrons in the ionic complex as well as that in the bare (C60(CN)n)n− are delocalized mainly on the unsaturated carbon centers of the fullerene unit, while the CN groups remain as a neutral unit. The MESP minimum (Vmin) values of (C60(CN)n)n− on the carbon cage have shown that the addition of each CN− unit on the cage enhances the negative character of Vmin by ∼54.7 kcal mol−1. This enhancement in MESP is comparable to the enhancement observed when one electron is added to C60 to produce (−62.5 kcal mol−1) and suggests that adding 'n' CN− groups to the fullerene cage is equivalent to supplying 'n' electrons to the carbon cage. Also the high capacity of the fullerene cage to hold several electrons can be attributed to the spherical delocalization of them onto the electron deficient carbon cage. The interactive behavior of CO2 molecules with (IM+)n⋯(C60(CN)n)n− systems showed that the interaction becomes stronger from −2.3 kcal mol−1 for n = 1 to −18.6 kcal mol−1 for n = 6. From the trianionic fulleride onwards, the C⋯CO2 noncovalent (nc) interaction changes to C–CO2 covalent (c) interaction with the development of carboxylate character on the adsorbed CO2. These results prove that cyano-fullerides are promising candidates for CO2 capture. [ABSTRACT FROM AUTHOR]