Lutetium Texaphyrin-Celecoxib Conjugate as a Potential Immuno-Photodynamic Therapy Agent.

Immuno-photodynamic therapy (IPDT) has emerged as a new modality for cancer treatment. Novel photosensitizers can help achieve the promise inherent in IPDT, namely, the complete eradication of a tumor without recurrence. We report here a small molecule photosensitizer conjugate, LuCXB. This IPDT agent integrates a celecoxib (cyclooxygenase-2 inhibitor) moiety with a near-infrared absorbing lutetium texaphyrin photocatalytic core. In aqueous environments, the two components of LuCXB are self-associated through inferred donor-acceptor interactions. A consequence of this intramolecular association is that upon photoirradiation with 730 nm light, LuCXB produces superoxide radicals (O2-•) via a type I photodynamic pathway; this provides a first line of defense against the tumor while promoting IPDT. For in vivo therapeutic applications, we prepared a CD133-targeting, aptamer-functionalized exosome-based nanophotosensitizer (Ex-apt@LuCXB) designed to target cancer stem cells. Ex-apt@LuCXB was found to display good photosensitivity, acceptable biocompatibility, and robust tumor targetability. Under conditions of photoirradiation, Ex-apt@LuCXB acts to amplify IPDT while exerting a significant antitumor effect in both liver and breast cancer mouse models. The observed therapeutic effects are attributed to a synergistic mechanism that combines antiangiogenesis and photoinduced cancer immunotherapy.

Theoretical insight into the doubly antiaromatic carbon allotrope cyclo[16]carbon.

A new carbon allotrope, cyclo[16]carbon (C16), has recently been successfully synthesized. It is hypothesized to exhibit double antiaromatic properties owing to the 4n π electrons. Theoretical calculations are a feasible method for systematically studying the structures and properties of unstable antiaromatic molecules. The results show that C16 has a planar structure characterized by alternating long and short bonds with D8h, and a strong antiaromatic characteristic originates from the two perpendicular π systems. We performed an extensive comparative analysis of C16 and the aromatic cyclo[18]carbon, C18. This study offers valuable insight into the structural and electronic characteristics of C16 and could inspire innovative applications and avenues for its utilization in various fields.

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.

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.

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.

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.

Insights into the Mechanism of Ground and Excited State Double Proton Transfer Reaction in Formic Acid Dimer.

The mechanism of ground and excited state double proton transfer reaction in formic acid dimer has been analyzed with the help of reaction force and the reaction electronic flux. The separation of reaction electronic flux in terms of electronic activity and reactivity, NBO, and dual descriptor lends additional support for the mechanism. Interestingly we found that the ground state double proton transfer mechanism is concerted synchronic, whereas the excited state double proton transfer is concerted asynchronic in nature.

Insights into the activation process of CO2 through Dihydrogenation reaction.

Based on first principle calculation, activation of CO2 has been analyzed thoroughly by using different conceptual density functional theory based descriptors like reaction force, reaction force constant, reaction electronic flux, dual descriptor, etc. via dihydrogenation reaction of B3N3, H2 and CO2. The total reaction is a two-step reaction where initially B3N3H2 is formed from the reaction between B3N3 and H2 and in the second step HCOOH is form due to the reaction of CO2 by B3N3H2. It has been found that the di-hydrogen reaction for the CO2 activation is endothermic in nature, which can be changed to exothermic reaction by applying proper external electric field. Movement of H2 plays an important role in the CO2 activation process. The reaction force constant, Wiberg bond index and its derivative reveal that the reaction is slightly asynchronous and concerted in nature.

Tailoring the properties of manganocene: formation of magnetic superalkali/superhalogen.

A new magnetic superalkali/superhalogen molecule based on the sandwich complex manganocene is reported. The hydrogen atoms of the cyclopentadienyl rings are periodically substituted with electron-donating and electron-withdrawing ligands (or both) to design substituted manganocene complexes. The substituted manganocene complexes exhibit the properties of superalkali and/or superhalogen depending on the nature of the substituents. The substituents, therefore, act as "switches" that can modify the properties of the parent manganocene moiety by keeping its magnetic nature intact. The substituted complexes also show marked nonlinear optical behavior.

Zintl superalkalis as building blocks of supersalts.

Alkali metal cations and halogen anions are common components of ionic salts. Recently, a new class of salts termed supersalts was reported, each of which contains a superalkali and a superhalogen that mimic an alkali metal cation and a halogen anion, respectively. Using three different functionals, namely B3LYP, wB97X, and M06-2X, we theoretically investigated a new subset of supersalts composed of Zintl-based superalkalis and inorganic superhalogens via computational modeling. The calculated dipole moment and first-order hyperpolarizability values for these supersalts indicate that they present nonlinear optical (NLO) behavior. The supersalts of Zintl superalkalis (Ca2P7, Sr2P7, Ba2P7) and superhalogens (BF4, BeF3, NO3) studied here were found to be stable. Graphical Abstract Using the first-principles calculation, a new class of supersalts by using Zintl-based superalkalis and inorganic superhalogens has been designed.

On the making of aromatic organometallic superalkali complexes.

Superalkalis are complexes that have a lower ionization energy than that of the corresponding alkali and alkaline earth metals. Based on First Principles calculations, the plausible existence of a superalkali complex consisting of an all-metal aromatic trigonal Au3 core coupled with pyridine (Py) and imidazole (IMD) ligands is suggested. The calculated ionization energy (IE) values of the subsequent organometallic complexes, Au3(Py)3 and Au3(IMD)3, are low, thereby mimicking the usual behavior of a superalkali. First order hyperpolarizability calculations show the existence of non-linear optical properties in some of the complexes, which is also on par with the properties of a superalkali.

Li@organic superhalogens: possible electrolytes in Li-ion batteries.

Inorganic superhalogens are commonly used as anionic counterparts in Li-ion batteries. In an endeavour to prepare better electrolytes, we have modelled the anionic part with different organic heterocyclic-based superhalogens. First principles calculations on those organic superhalogens reveal that the Li-binding energy is at par with that of the Li-salt of a common electrolyte. Out of five different halogen free organic heterocycles, Li[C3BN2(NO2)4] and Li[C2BNO(NO2)3] are found to be mostly suitable as electrolytes in Li-ion batteries. Molecular dynamics simulation studies on C2BNO(NO2)3-, C3BN2(NO2)4-, Li[C2BNO(NO2)3] and Li[C3BN2(NO2)4] also reveal that the structures are dynamically stable.

Functionalized deltahedral Zintl complexes Ge9R3 (R = CF3, CN, and NO2): a new class of superhalogens.

The assembly of atoms leads to the formation of clusters. These clusters have a tendency to gain their stability by forming either cations or anions. Among the anionic clusters, Zintl ions with multiple negative charges are a special type of inorganic complex generally formed from group 13, 14 and 15 elements in the periodic table. On the other hand, superhalogens are neutral molecules which have high electron affinity. Between the two different types of molecules, the former stabilized in the neutral state by forming a phase with alkali metal atoms, while the latter prefers the anionic state. Using first principle calculations, we show that it is also possible to design superhalogens having a Zintl core by functionalizing with suitable ligands like CF3, CN and NO2. The vertical detachment energies of these complexes indicate that they can be classified as superhalogens. The stability of these complexes is explained in terms of the jellium model. Density of states, partial density of states and natural localized molecular orbitals (NLMO) of these molecules lend additional information on the structure and bonding of these complexes.