New insights into the mechanism of triplet radical-pair combinations. The persistent radical effect masks the distinction between in-cage and out-of-cage processes

Steady-state and laser-pulsed irradiations of dibenzyl ketone (ACOB0) and derivatives with a p-methyl or a p-hexadecyl chain (ACOB1 and ACOB16, respectively) have been conducted in polyethylene films with 0, 46, and 68% crystallinities. Calculation of the fractions of in-cage combinations of the triplet benzylic radical-pair intermediates based on photoproduct yields, Fc, from ACOB16 are shown to be incorrect as a result of the kinetic consequences of drastically different diffusion coefficients for the benzyl and p-hexadecylbenzyl radicals. Careful analyses of the transient absorption traces, based upon a new model developed here, allow the correct cage effects to be determined even from ACOB0. The model also permits the rate constants for radical-pair combinations and escape from their cage of origin to be calculated using either an iterative fitting procedure or a very simple one which requires only k-CO and the intensities of the transient absorption immediately after the flash and after the in-cage portion of reaction by the benzylic radicals is completed. Values of the rate constant for decarbonylation of the initially formed arylacetyl radicals, k-CO, have been measured from the rise portions of the laser-flash transient absorption traces. They confirm the assertion from results in liquid alkane media that decarbonylation rates are independent of microviscosity. The data separate components of a reaction from an (in-cage) "cage effect" and an (out-of-cage) "persistent radical effect" that are responsible for formation of AB-type (i.e., decarbonylated) products. The effects here are a consequence of vastly different rates of diffusion for coreacting A. and B. benzylic radicals rather than segregation of the radicals in different parts of a hetereogeneous environment (which leads to an excess of AA and BB products). Heretofore, observation of exclusive formation of AB products has been attributed to in-cage combinations of geminate radical pairs. We show that not to be the case here and provide methodologies which may be used for testing the importance of the "persistent radical effect" component of reaction.     

Determination of disulfiram by micellar liquid chromatography in illicit preparations

Presently, disulfiram is used in aversion therapy for recovering alcoholics. It acts by inhibiting aldehyde dehydrogenase, leading to high blood levels of acetaldehyde. A simple direct injection micellar liquid chromatographic procedure was developed to determine disulfiram in illicit preparations (ayurvedic, herbal, divine ash, and traditional medicine), as well as in pharmaceuticals and biological samples (urine). After application of a predictive optimization strategy, the proposed method was developed using a 0.1 M sodium dodecyl sulfate-butanol 4% (v/v) buffered to pH 7 as the mobile phase at a flow rate of 1 mL/min, an octyl silyl (C8) 150 mm column, and diode array detection at 248 nm. Under the above conditions, the analysis time was below 8 min. Validation studies were based on U.S. Food and Drug Administration guidelines. The LOD (3 x SD criterion) was 15 ng/mL and LOQ (10 x SD criterion) was 70 ng/mL for disulfiram. The intraday and interday precisions were below 3.5%, recoveries were in the range of 97-102%, and robustness was below 3%. The optimized and validated micellar liquid chromatographic method was successfully applied to the determination of disulfiram in ayurvedic, herbal, divine ash, and other samples. The procedure developed could also be used in the fields of QC, routine analysis, and pharmacokinetic studies.     

Synthesis and binding studies of novel diethynyl-pyridine amides with genomic promoter DNA G-quadruplexes

Herein, we report the design, synthesis and biophysical evaluation of novel 1,2,3-triazole-linked diethynyl-pyridine amides and trisubstituted diethynyl-pyridine amides as promising G-quadruplex binding ligands. We have used a Cu(I)-catalysed azide-alkyne cycloaddition click reaction to prepare the 1,2,3-triazole-linked diethynyl-pyridine amides. The G-quadruplex DNA binding properties of the ligands have been examined by using a F?rster resonance energy transfer (FRET) melting assay and surface plasmon resonance (SPR) experiments. The investigated compounds are conformationally flexible, having free rotation around the triple bond, and exhibit enhanced G-quadruplex binding stabilisation and specificity between intramolecular promoter G-quadruplex DNA motifs compared to the first generation of diaryl-ethynyl amides (J. Am. Chem. Soc. 2008, 130, 15950-15956). The ligands show versatility in molecular recognition and promising G-quadruplex discrimination with 2-50-fold selectivity exhibited between different intramolecular promoter G-quadruplexes. Circular dichroism (CD) spectroscopic analysis suggested that at higher concentration these ligands disrupt the c-kit2 G-quadruplex structure. The studies validate the design concept of the 1,3-diethynyl-pyridine-based scaffold and demonstrate that these ligands exhibit not only significant selectivity over duplex DNA but also variation in G-quadruplex interaction properties based on small chemical changes in the scaffold, leading to unprecedented differential recognition of different DNA G-quadruplex sequences.     

Total synthesis of (+)-(2'S,3'R)-zoapatanol exploiting the B-alkyl Suzuki reaction and the nucleophilic potential of the sulfinyl group

A stereoselective synthesis of the diterpenoid oxepane (+)-zoapatanol is described. The key steps include a B-alkyl Suzuki cross-coupling reaction for the stereoselective synthesis of trisubstituted alkenes, creation of the two stereogenic centers on the oxepane ring by heterofunctionalization of an alkene through substrate control exploiting the nucleophilic potential of an intramolecular sulfinyl group, and transformation of a β-hydroxy sulfoxide into a terminal alkene.     

Cucurbit[n]uril based supramolecular assemblies: tunable physico-chemical properties and their prospects

This Feature Article provides an account of the recent work by our research group (with some reference to relevant work of other groups) on the spectacular physico-chemical properties of cucurbituril-based supramolecular assemblies of chromophoric dyes having technological and biological importance. Simultaneous association of multiple hosts or guests either by cooperative binding or competitive displacement is an applied strategy to construct novel functional assemblies with predesignated characteristics. Here, effort has been made to briefly discuss the diverse photophysical characteristics of several host-guest complexes and the dynamic responses of such molecular assemblies towards external stimulants like metal ions. The detailed experimentation on these assemblies project their applications in the controlled uptake and release of drugs, photofunctional devices, aqueous-based dye lasers, and molecular architectures.     

Adaptive modified function projective synchronization of multiple time-delayed chaotic Rossler system

In this Letter we consider modified function projective synchronization of unidirectionally coupled multiple time-delayed Rossler chaotic systems using adaptive controls. Recently, delay differential equations have attracted much attention in the field of nonlinear dynamics. The high complexity of the multiple time-delayed systems can provide a new architecture for enhancing message security in chaos based encryption systems. Adaptive control can be used for synchronization when the parameters of the system are unknown. Based on Lyapunov stability theory, the adaptive control law and the parameter update law are derived to make the state of two chaotic systems are function projective synchronized. Numerical simulations are presented to demonstrate the effectiveness of the proposed adaptive controllers.     

Rapid Access to Substituted Indenones through Grignard Reaction and Its Application in the Synthesis of Fluorenones Using Ring Closing Metathesis

An efficient, one-step method has been used to access a variety of substituted indenones in a regiospecific manner by Grignard addition to indene-1,3-dione. This method provides straightforward access to natural products such as neo-lignans and isoampelopsin D analogues. Moreover, diallyl indenones have been synthesized and employed as ring-closing metathesis (RCM) precursors for the facile synthesis of substituted fluorenone derivatives through an RCM-aromatization sequence.     

Cooperative catalysis approach to intramolecular hydroacylation

Prior examples of hydroacylation to form six- and seven-membered ring ketones require either embedded chelating groups or other substrate design strategies to circumvent competitive aldehyde decarbonylation. A cooperative catalysis strategy enabled intramolecular hydroacylation of disubstituted alkenes to form seven- and six-membered rings without requiring substrate-embedded chelating groups.     

Cover Picture: Expanding the Toolbox of Target Directed Bio-Orthogonal Synthesis: In Situ Direct Macrocyclization by DNA Templates (Angew. Chem. Int. Ed. 7/2023)

Herein, we demonstrate for the first time that noncanonical DNA can direct macrocyclization-like challenging reactions to synthesize gene modulators. The planar G-quartets present in DNA G-quadruplexes (G4s) provide a size complementary reaction platform for the bio-orthogonal macrocyclization of bifunctional azide and alkyne fragments over oligo- and polymerization. G4s immobilized on gold-coated magnetic nanoparticles have been used as target templates to enable easy identification of a selective peptidomimetic macrocycle. Structurally similar macrocycles have been synthesized to understand their functional role in the modulation of gene function. The innate fluorescence of the in situ formed macrocycle has been utilized to monitor its cellular localization using a G4 antibody and its in cell formation from the corresponding azide and alkyne fragments. The successful execution of in situ macrocyclization in vitro and in cells would open up a new dimension for target-directed therapeutic applications.