In Silico Investigation of the Mechanism of Disulfide Bond Dissociation by New Frustrated Lewis Pairs.

Understanding the mechanism of disulfide bond cleavage is important in various scientific disciplines including organic synthesis, catalysis, and biochemistry. In this study, an in silico investigation has been carried out for the dissociation of disulfide bonds using newly designed frustrated Lewis pairs (FLPs). The study revealed that the cleavage of the disulfide bond by the FLP P(tBu)3/B(C2NBSHF2)3 can also be used like the conventional FLP (tBu)3P/B(C6F5)3. It has been observed that the reaction is almost thermoneutral in the gas phase but exothermic in nonpolar solvents, such as toluene, heptane, and hexane. Furthermore, the natural bond orbital (NBO) describes insights into the role of FLPs in facilitating this reaction. Additionally, reaction force and force constant studies shed light on the energy requirements for completing the reaction and the synchronous nature of the dissociation process, respectively. Reaction electronic flux (REF) and its separations give the pattern of electronic activity during the chemical reaction. Extended transition state-natural orbitals for chemical valence (ETS-NOCV) and principal interacting orbital (PIO) analysis provide valuable information about the orbital interactions during the chemical reaction.

Concept-Driven Chemoselective O/N-Derivatization of Prolinol: A Bee-Line Approach to Access Organocatalysts.

An investigation into the sensitivity of reaction conditions to a highly utilized protocol has been reported, wherein the mono-Boc functionalization of prolinol could be controlled for the exclusive synthesis of either N-Boc, O-Boc, or oxazolidinone derivatives. Mechanistic investigation revealed that the elementary steps could possibly be controlled by (a) a requisite base to recognize the differently acidic sites (NH and OH) for the formation of the conjugate base, which reacts with the electrophile, and (b) the difference in nucleophilicity of the conjugate basic sites. Herein, a successful chemoselective functionalization of the nucleophilic sites of prolinol by employing a suitable base is reported. This has been achieved by exploiting the relative acidity difference of NH and OH along with the reversed nucleophilicity of the corresponding conjugate bases N- and O-. This protocol has also been used for the synthesis of several O-functionalized prolinol derived organocatalysts, few of which have been newly reported.

Insights into the catalytic activity of boron-doped thiazoles in the Diels-Alder reaction.

The role of boron-doped thiazoles as a Lewis acid catalyst in [4+2] cycloaddition reaction between 1,3-butadiene and acrolein has been addressed. Three different organic heterocycles were designed to study their catalytic activity. It has been observed that these heterocycles efficiently work as catalysts than the well-known Lewis acid BF3. All the reactions follow the normal electron demand process and are exothermic. Different conceptual DFT-based reactivity descriptors and electronic structure principles such as maximum hardness and minimum electrophilicity lend additional support to the feasibility of the reaction mechanism. The reaction force (RF), reaction electronic flux (REF), and its different components exhibit a detailed electronic activity throughout the reaction.

Functionalized nona-silicide [Si9R3] Zintl clusters: a new class of superhalogens.

Superatoms, due to their various applications in redox and materials chemistry, have been a major topic of study in cluster science. Superhalogens constitute a special class of superatoms that mimic the chemistry of halogens and serve as building blocks of novel materials such as super and hyper salts, perovskite-based solar cells, solid-state electrolytes, and ferroelectric materials. These applications have led to a constant search for new class of superhalogens. In this study, using density functional theory, we show that recently synthesized [Si9{Si (tBu)2H}3] and [Si9{Si (TMS)3}3] Zintl clusters not only behave like halogens but also when functionalized with suitable ligands exhibit superhalogen characteristics. Frontier molecular orbital (FMO) analyses give insights into the electron-accepting nature of the Zintl clusters. Additional bonding techniques such as energy density at the bond critical point (BCP) and adaptive natural density partitioning (AdNDP) gives complementary information about the nature of bonding in Si9-based Zintl clusters. The potential of these Zintl clusters in the synthesis of new electrolytes in Li-ion batteries is also investigated.

Role of Size and Composition on the Design of Superalkalis.

Superalkalis and superhalogens are atomic clusters that mimic the chemistry of alkali and halogen atoms, respectively; the ionization energies of the superalkalis are less than those of alkali atoms, while the electron affinities of superhalogens are larger than those of the halogen atoms. These superions can serve as the building blocks of a new class of supersalts with applications in solar cells, metal-ion batteries, multiferroic materials, and so on. While considerable progress has been made in the design and synthesis of superhalogens, a similar understanding of superalkalis is lacking. Using density functional theory with hybrid exchange-correlation functional and Gaussian basis sets, we have systematically studied the role of size and composition on the properties of two different classes of clusters whose stabilities are governed by the Wade-Mingos polyhedral skeletal electron pair theory. One class belongs to the closo-borane family LimBnXn (m = 1, 2, 3; n = 6, 12; X = H, F, CN), while the other to the Zintl ions Lim[Be@Ge9]. We show that Li3BnXn and Li3[Be@Ge9] clusters are superalkalis with ionization energies as low as 2.84 eV in Li3B6H6. However, contrary to expectation, the ionization energies do not decrease with increasing cluster volume. Instead, ionization energies are linked to the X ligands' electron affinities; the larger the electron affinity, the higher is the ionization energy. The understanding gained here will help in the discovery of superalkalis and, hence, enrich the library of supersalts.

Zintl Lewis Superacids: Al(Ge9L3)3 (L = H, CH3, CHO, CN).

In quest of a Zintl ion-based Lewis superacids, Al(Ge9L3)3 {L= H, CH3, CHO and CN} compounds have been designed and their properties have been studied within the framework of conceptual density functional theory-based reactivity descriptors. Superacid property has been identified for these complexes as per the fluoride ion affinity (FIA) values. Studies reveal that Al[Ge9(CN)3]3 and Al[Ge9(CH3)3]3 behave like superacids as their FIA exceeds the value of SbF5, which is considered as the strongest Lewis acid. It has been observed that the ligand plays an important role in reactivity as well as in Lewis acidic property.

Unraveling the origin of interactions of hydroxychloroquine with the receptor-binding domain of SARS-CoV-2 in aqueous medium.

Interactions of hydroxychloroquin (HCQ) with the receptor binding domain (RBD) of SARS-CoV-2 were studied from atomistic simulation and ONIOM techniques. The key-residues of RBD responsible for the human transmission are recognized to be blocked in a heterogeneous manner with the favorable formation of key-residue:HCQ (1:1) complex. Such heterogeneity in binding was identified to be governed by the differential life-time of the hydrogen bonded water network anchoring HCQ and the key-residues. The intermolecular proton transfer facilitates the most favorable Lys417:HCQ complexation. The study demonstrates that off-target bindings of HCQ need to be minimized to efficiently prevent the transmission of SARS-CoV-2.

Oxidation-Induced Differentially Selective Turn-On Fluorescence via Photoinduced Electron Transfer Based on a Ferrocene-Appended Coumarin-Quinoline Platform: Application in Cascaded Molecular Logic.

Differentially selective molecular sensors that exhibit differential response toward multiple analytes are cost-effective and in high demand for various practical applications. A novel, highly differentially selective electrochemical and fluorescent chemosensor, 5, based on a ferrocene-appended coumarin-quinoline platform has been designed and synthesized. Our designed probe is very specific toward Fe3+ via a reversible redox process, whereas it detects Cu2+ via irreversible oxidation. Interestingly, it exhibits differential affinity toward the Cu+ ion via complexation. High-resolution mass spectrometry, 1H NMR titration, and IR spectral studies revealed the formation of a bidentate Cu+ complex involving an O atom of the amide group attached to the quinoline ring and a N atom of imine unit, and this observation was further supported by quantum-chemical calculations. The metal binding responses were further investigated by UV-vis, fluorescence spectroscopy, and electrochemical analysis. Upon the addition of Fe3+ and Cu2+ ions, the fluorescence emission of probe 5 shows a "turn-on" signal due to inhibition of the photoinduced electron transfer (PET) process from a donor ferrocene unit to an excited-state fluorophore. The addition of sodium l-ascorbate (LAS) as a reducing agent causes fluorescence "turn off" for the Fe3+ ion because of reemergence of the PET process but not for the Cu2+ ion because it oxidizes the ferrocene unit to a ferrocenium ion with its concomitant reduction to Cu+, which further complexes with 5. Thermodynamic calculations using the Weller equation along with density functional theory calculations validate the feasibility of the PET process. A unique combination of Fe3+, LAS, and Cu2+ ions has been used to produce a molecular system demonstrating combinational "AND-OR" logic operation.

Designing aromatic heterocyclic superacids in terms of Brønsted and Lewis perspectives.

The unexplored area of organic superacids was investigated in terms of both Brønsted and Lewis concepts of acids and bases. The primary requirement of a superacid-high affinity for electron/fluoride ions was fulfilled using two strategies: (i) using the superhalogen-type heterocyclic framework and (ii) selecting systems that have an electron count one short of attaining (4n + 2) Hückel aromaticity. With these in mind, eleven systems were considered throughout the study, expected to cross the target of 100% H2SO4 acidity and/or the fluoride affinity of SbF5. To enhance the pKa and F- affinity values of the considered systems, electron-withdrawing ligands F and CN were employed. The superhalogen and aromaticity properties were verified by vertical detachment energy (VDE) and nucleus independent chemical shift (NICS) calculations, respectively. Finally, the collective effect of the potential super Lewis acids was looked into using a BL3 skeleton with them acting as ligands.

Cycloaddition Reactions between H2C = CHR (R = H, CN, CH3) and a Cyclic P/B Frustrated Lewis Pair: A DFT Study.

The cycloaddition of ethylene, cyanoethylene, and propylene to a five-membered P/B frustrated Lewis pair (FLP) is shown to be highly favorable under normal conditions, as confirmed by the computed thermodynamic and kinetic data. All of these cycloaddition reactions are concerted as highlighted by the intrinsic reaction coordinate (IRC) and Wiberg bond index calculations. Almost 70% of the reaction force is required for structural orientation to initiate electronic activity. The reactions are interpreted by the frontier molecular orbital (FMO) analysis and conceptual density functional theory (DFT)-based reactivity descriptors. It appears that ethylene and propylene will act as nucleophiles, while the FLP will act as an electrophile throughout the cycloaddition reaction, however, cyanoethylene will act as an electrophile and the FLP as a nucleophile. Regioselectivities of the cycloadditon of cyanoethylene and propylene to the FLP are further verified through philicity and dual descriptors. It is demonstrated that an FLP can be forced to act as an electrophile or a nucleophile by intelligently selecting its partner in a cycloaddition reaction. Even the P and B centers would behave differently within the same FLP. This strategy may be properly exploited by the experimentalists in designing a suitable reaction for the synthesis of any useful molecule possessing the desired property.

Density Functional Treatment on Alkylation of a Functionalized Deltahedral Zintl Cluster.

Density functional theory (DFT) is one of the popular methods to understand the electronic structure of molecular systems based on electronic density. On the basis of this theory, several conceptual DFT descriptors have been developed which can deal with the stability, reactivity, and several other physicochemical properties of molecules. Here, we have taken a nine-atom-functionalized deltahedral Zintl cluster of germanium (Ge) to examine the alkylation reaction mechanism. The study showed that the Zintl cluster having a methyl group as a ligand, [Ge9(CH3)3-], acts as a better nucleophile than the cyanide (-CN)-substituted cluster [Ge9(CN)3-] in terms of different thermodynamic parameters like free energy, enthalpy of activation, reaction energy, etc. A detailed reaction electronic flux analysis reveals the nature of the electronic activity throughout the reaction pathway. The reaction force, Wiberg bond indices, and dual descriptor lend additional support to the reaction mechanism. It has been found that the alkylation reaction between the Zintl ion and the alkyl halide follows a SN2-like mechanism.

Superhalogens as Building Blocks of Super Lewis Acids.

Lewis acids play an important role in synthetic chemistry. Using first-principle calculations on some newly designed molecules containing boron and organic heterocyclic superhalogen ligands, we show that the acid strength depends on the charge of the central atom as well as on the ligands attached to it. In particular, the strength of the Lewis acid increases with increasing electron withdrawing power of the ligand. With this insight, we highlight the importance of superhalogen-based ligands in the design of strong Lewis acids. Calculated fluoride ion affinity (FIA) values of B[C2 BNO(CN)3 ]3 and B[C2 BNS(CN)3 ]3 show that these are super Lewis acids.

A New Class of Superhalogen Based Anion Receptor in Li-Ion Battery Electrolytes.

In the search for new additives (anion receptors) in Li-ion battery electrolytes especially for LiPF6 and LiClO4, we have theoretically designed boron-based complexes by coupling with different heterocyclic ligands. The validation of the formation of modeled compounds involves reproduction of available experimentally reported absolute magnetic shielding and chemical shift values for different boron complexes. As compared to the commonly used tris(pentafluorophenyl) borane, our designed compounds suggest that the complexes like B[C2HBNO(CN)2]3, B[C2HBNS(CN)2]3, and B[C4H3BN(CN)2]3 are promising additives.

Ligand stabilization of manganocene dianions - in defiance of the 18-electron rule.

Manganocene [Mn(C5H5)2], a 17-electron system, is expected to have a high electron affinity, as addition of an extra electron would make it a closed-shell 18-electron system. Surprisingly, it has a very low electron affinity of only 0.28 eV. Combined with its high ionization potential of around 7.0 eV, manganocene, therefore, should not be eager to either donate or accept an electron. We show that this property can be fundamentally altered with the proper choice of ligands, even though the total electron count remains the same. For example, the electron affinities of manganocene-derivatives Mn[C5(CN)5]2 and Mn[C5(BO)5]2, created by replacing H with CN or BO, are found to be 4.78 eV and 4.85 eV, respectively, making these species superhalogens. The power of the ligands is further demonstrated by studying the stability of their di-anions. Note that [Mn(C5X5)2]2- (X = H, CN, BO) di-anions, with 19-electrons, have one electron more than necessary to satisfy the 18-electron rule for stability. This factor, combined with the unavoidable repulsion between the two extra electrons, should destabilize [Mn(C5X5)2]2-. While that is the case for [Mn(C5H5)2]2-, we show that both Mn[C5(CN)5]22- and Mn[C5(BO)5]22- are stable against auto-detachment of the second electron by 0.7 eV and 0.38 eV, respectively. These results, based on first-principles calculations, demonstrate that ligand-manipulation can be used as an effective strategy to design and synthesize new materials with novel and tailored properties.

Unique reactivity of B in B[Ge9Y3]3 (Y = H, CH3, BO, CN): formation of a Lewis base.

Boron compounds usually exhibit Lewis acidity at the boron center due to the presence of vacant p-orbitals. We show that this chemistry can be altered by an appropriate choice of ligands to decorate the boron center. To elucidate this effect, we studied the interactions of boron with two classes of ligands, one based on penta-substituted phenyl species (C6X5, X = F, BO, CN) and the other based on Zintl-ion-based groups (Ge9Y3, Y = H, CH3, BO, CN). An in-depth analysis of the charges and Fukui function values at the local atomic sites of the substituted boron derivatives B(C6X5)3 and B[Ge9Y3]3 shows that the B-center in the former is electrophilic, while it is nucleophilic in the latter. The chemical stability of the B[Ge9Y3]3 species is shown to be due to the presence of strong 2c-2e bonds between the B and Ge centers. Thus, the general notion of the Lewis acid nature of a boron center depends upon the choice of the ligand.

Negative influence of pKa on activation energy barrier: A case study for double proton transfer reaction in inorganic acid dimers.

Strength of acid can be determined by means of pKa value. Attempts have been made to find a relationship between pKa and activation energy barrier for a double proton transfer (DPT) reaction in inorganic acid dimers. Negative influence of pKa is observed on activation energy (Ea ) which is contrary to the general convention of pKa . Four different levels of theories with two different basis sets have been used to calculate the activation energy barrier of the DPT reaction in inorganic acid dimers. A model based on first and second order polynomial has been created to find the relationship between activation energy for DPT reaction. © 2018 Wiley Periodicals, Inc.

Deltahedral Organo-Zintl Superhalogens.

Zintl ions constitute a special type of naked anionic clusters, mainly consisting of Group 13, 14, and 15 elements of the Periodic Table. Due to the presence of multiple negative ions, the chemistry of Zintl ions is unique. They not only form Zintl phases with alkali and alkaline-earth metal cations, but also form organo-Zintl clusters with distinct properties. By first-principles calculations based on density functional theory, we have designed a new deltahedral organo-Zintl cluster with Ge94- as the core and aromatic heterocyclic compounds as ligands. Calculations on such complexes show that they form a special class of system known as a superhalogen (SH), with a high vertical detachment energy of 4.9 eV. The density of states (DOS), partial DOS, and different molecular orbitals give additional information about the bonding features of the complexes.

Atom-Economical Palladium Carbon-Catalyzed de Novo Synthesis of Trisubstituted Nicotinonitriles.

A de novo palladium carbon-catalyzed synthesis of trisubstituted nicotinonitriles from easily synthesized homopropagylic or homoallylic aromatic alcohols in the presence of nitriles has been explored. The mechanism proceeds with an interesting generation of a Pd(II)-C palladacycle followed by an oxidative aromatization to generate the pyridine core. The pyridine core is generated with a noteworthy C-C bond cleavage in the case of the substituted nitriles. The moderate yields and easy separation of the products lend a unique importance to this one-pot methodology.

Controlled Energy Transfer from a Ligand to an EuIII Ion: A Unique Strategy To Obtain Bright-White-Light Emission and Its Versatile Applications.

A new diphenylamine-functionalized ancillary-ligand-coordinated europium(III) ß-diketonate complex showed incomplete photoexcitation energy transfer from a ligand to a EuIII ion. A solvatochromism study led to a balancing of the primary colors to obtain single-molecule white-light emission. Thermal-sensing analysis of the europium complex was executed. The europium complex, conjugated with a near-UV-light-emitting diode (395 nm), showed appropriate white-light-emission CIE color coordinates (x = 0.34 and y = 0.33) with a 5152 K correlated color temperature.

Residue Specific Interaction of an Unfolded Protein with Solvents in Mixed Water-Ethanol Solutions: A Combined Molecular Dynamics and ONIOM Study.

The molecular mechanism of ethanol governed unfolding of an enzymatic protein, chymotrypsin inhibitor 2 (CI2), in water-ethanol mixed solutions has been studied by using combined molecular dynamics simulations and ONIOM study. The residue specific solvation of the unfolded protein and the interactions between the individual amino acid residues of the protein with ethanol as well as water have been investigated. The results are compared with that obtained from the folded state of the protein. Further, emphasis has been given to explore the residue's preferential site of attraction toward the nature of the solvents. The heterogeneous structuring of water and ethanol around the hydrophobic and hydrophilic surfaces of the protein is found to correlate well with their available surface areas to the solvents. Both hydrophobic and hydrophilic interactions are found to have important contributions in rupturing protein's secondary structural segments. Further, residue-water as well as residue-ethanol binding energies show significant involvement of the hydrogen bonding environment in the unfolding process; particularly, residue-water hydrogen bonds are found to play an indispensable role.