A density functional theory analysis of the C-H activation reactivity of iron(IV)-oxo complexes with an 'O' substituted tetramethylcyclam macrocycle.

In this article, we present a meticulous computational study to foresee the effect of an oxygen-rich macrocycle on the reactivity for C-H activation. For this study, a widely studied nonheme Fe(IV)O molecule with a TMC (1,4,8,11-tetramethyl 1,4,8,11-tetraazacyclotetradecane) macrocycle that is equatorially attached to four nitrogen atoms (designated as N4) and acetonitrile as an axial ligand has been taken into account. For the goal of hetero-substitution, step-by-step replacement of the N4 framework with O atoms, i.e., N4, N3O1, N2O2, N1O3, and O4 systems, has been considered, and dihydroanthracene (DHA) has been used as the substrate. In order to neutralise the system and prevent the self-interaction error in DFT, triflate counterions have also been included in the calculations. The study of the energetics of these C-H bond activation reactions and the potential energy surfaces mapped therefore reveal that the initial hydrogen abstraction, which is the rate-determining step, follows the two-state reactivity (TSR) pattern, which means that the originally excited quintet state falls lower in the transition state and the product. The reaction follows the hydrogen atom transfer (HAT) mechanism, as indicated by the spin density studies. The results revealed a fascinating reactivity order, in which the reactivity increases with the enrichment of the oxygen atom in the equatorial position, namely the order follows N4 < N3O1 < N2O2 < N1O3 < O4. The impacts of oxygen substitution on quantum mechanical tunneling and the H/D kinetic isotope effect have also been investigated. When analysing the causes of this reactivity pattern, a number of variables have been identified, including the reactant-like transition structure, spin density distribution, distortion energy, and energies of the electron acceptor orbital, i.e., the energy of the LUMO (σ*z2), which validate the obtained outcome. Our results also show very good agreement with earlier combined experimental and theoretical studies considering TMC and TMCO-type complexes. The DFT predictions reported here will undoubtedly encourage experimental research in this biomimetic field, as they provide an alternative with higher reactivity in which heteroatoms can be substituted for the traditional nitrogen atom.

Disseminated cysticercosis with multi-system involvement in a child.

We report a rare case of disseminated cysticercosis in a 7-year-old Indian girl with recent onset seizures treated with antiepileptics for 2 months. When she presented to dermatology clinic, she had multifocal subcutaneous and submucosal nodules. The subsequent diagnostic workup revealed extensive neurocysticercosis as well as orbital and myocysticercosis.

Role of "S" Substitution on C-H Activation Reactivity of Iron(IV)-Oxo Cyclam Complexes: a Computational Investigation.

A comprehensive density functional theory (DFT) investigation has been presented in this article to address the role of equatorial sulfur ligation in C-H activation. A non-heme iron-oxo compound with four nitrogen atoms constituting the equatorially connected macrocyclic framework (represented as N4) [Fe(IV)═O(THC)(CH3CN)]2+(THC = 1,4,8,11-tetrahydro1,4,8,11-tetraazacyclotetradecane) has been considered as the base compound. Other complexes have been anticipated by the sequential replacement of this nitrogen by sulfur, that is, N4, N3S1, N2S2, N1S3, and S4. Counterions, as always, have been considered to avoid the self-interaction error in DFT. Generally, the anti-conformers (with respect to equatorial N-H and Fe═O) turned out to be the most stable. It was found that with the enrichment of the equatorial sulfur atom, reactivity increases successively, that is, we get the trend N4 < N3S1 < N2S2 < N1S3 < S4. Our investigations have also verified the available experimental results where it has been reported that N2S2 is more reactive than N4 in their mixed conformation. In search of insights into this typical pattern of reactivity, the interplay of several factors has been recognized, such as the distortion energy which decreases for the transition states with the addition of sulfur; the spin density on the oxygen atom which increases implying that the radical character of abstractor increases on sulfur ligation; the energy of the electron acceptor orbital (the lowest unoccupied molecular orbital (σz2*)) which decreases continuously with the sulfur substitution; and the triplet-quintet oxidant energy gap which decreases consistently with S enrichment in the equatorial position. The computational predictions reported here, if further validated by experiments, will definitely encourage the synthesis of sulfur-ligated bio-inspired complexes instead of the ones constituting nitrogen exclusively.

Nevus Unius Lateris with Bilateral Oral Mucosal Lesions: An Unusual Presentation.

Verrucous epidermal nevi (VEN) are cutaneous hamartomas characterized by keratinocytic hyperplasia. Majority are linear in distribution and tend to follow the Blaschko lines; however, some may have zosteriform (segmental) or systematized distribution involving widespread areas of skin. The systematized ones are further classified into "Nevus Unius Lateris" when one-half of the body is affected, and "Ichthyosis Hystrix" showing bilateral distribution, both being the uncommon forms. Although it can affect any body part, it rarely involves the head and neck region with seldom involvement of mucosae, scalp, and ear lobes. We saw a 6-year-old child with multiple hyperpigmented verrucous plaques predominantly present over left half of the body, ipsilateral alopecia scalp, and verrucous lesions involving mucosae of palate and tongue, which were present bilaterally. Previously, case reports of oral lesions related to VEN had demonstrated segmental, midline, or unilateral distribution. Hereby, we report this peculiar case of Nevus Unius Lateris with bilateral oral mucosal involvement, owing to its rarity.

Formulation development and optimization of fast dissolving tablets of aceclofenac using natural superdisintegrant.

The current research work involves preparation of fast dissolving tablets of Aceclofenac by direct compression method using different concentrations of Lepidium sativum mucilage as natural superdisintegrant. A two-factor three-level (3(2)) factorial design is being used to optimize the formulation. Nine formulation batches (D1-D9) were prepared accordingly. Two factors as independent variables (X 1-amount of ß-cyclodextrin and X 2-amount of Lepidium sativum mucilage) were taken with three levels (+1, 0, -1). The levels of two factors were selected on the basis of preliminary experiments conducted and their effect on three dependent variables (disintegration time, wetting time, and in vitro drug release) was studied along with their % prediction error. All the active blends were evaluated for postcompression parameters (angle of repose, Carr's index, Hausner ratio, etc.) and the tablets were evaluated for postcompression parameters (weight variation, hardness, and friability, wetting time, disintegration time, water absorption ratio, and in vitro drug release studies). The optimum batch was further used for SEM and stability studies. Formulation D5 was selected by the Design-Expert software which exhibited DT (15.5 sec), WT (18.94 sec), and in vitro drug release (100%) within 15 minutes.