Rajendra Rathore

Excimericsystems (i.e., excited dimers) have well servedas modelcompounds for the study of the delocalization of electronic energyover weakly interacting chromophores. However, there remain relativelyfew isolated systems in which such interactions can be studied experimentallyat a level to afford detailed comparisons with theory. In this Article,we examine a series of covalently and noncovalently linked dimersof fluorene, as a model aromatic chromophore, where the formationof excimers requires a & pi;-stacked, cofacial orientation at vander Waals contact. Building upon a series of seminal prior studiesthat examined vibronic quenching of the excitation interaction invan der Waals dimers, the key question that we sought to address hereis whether a single quenching factor could reproduce experimentalexcitonic splittings across a series of covalently and noncovalentlylinked bichromophoric systems built from the same chromophore. Incomparing experimentally measured excitonic splittings with calculatedstatic splittings using time-dependent density functional methods,we find that all systems save one fall on a line with a slope of 0.080(8),reflecting a vibrational quenching of roughly 1 order of magnitude.The outlier, which shows a significantly reduced quenching factor,represents a cyclophane-linked system where the fluorene moietiesare constrained in a cofacial arrangement. We argue that this systemevidences the transition from the weak to intermediate coupling regime.

A study of cofacially arrayed π-systems is of particular importance for the design of functional materials for efficient long-range intra-chain charge transfer through the bulk semiconducting materials in the layers of photovoltaic devices. The effect of π-stacking between a pair of aromatic rings has been mainly studied in the form of cyclophanes, where aromatic rings are forced into a sandwich-like geometry, which extensively deforms the aromatic rings from planarity. The synthetic difficulties associated with the preparation of cyclophane-like structures has prevented the synthesis of many examples of their multi-layered analogues. Moreover, the few available multi-layered cyclophanes are not readily amenable to the structural modification required for the construction of D–spacer–A triads needed to explore mechanisms of electron and energy transfer. In this review, we recount how a detailed experimental and computational analysis of 1,3-diarylalkanes led to the design of a new class of cofacially arrayed polyfluorenes that retain their π-stacked structure. Thus, efficient synthetic strategies have been established for the ready preparation of monodisperse polyfluorenes with up to six π-stacked fluorenes, which afford ready access to D–spacer–A triads by linking donor and acceptor groups to the polyfluorene spacers via single methylenes. Detailed ¹H NMR spectroscopy, X-ray crystallography, electrochemistry, and He(I) photoelectron spectroscopy of F2–F6 have confirmed the rigid cofacial stacking of multiple fluorenes in F2–F6, despite the presence of rotatable C–C bonds. These polyfluorenes (F2–F6) form stable cation radicals in which a single hole is delocalized amongst the stacked fluorenes, as judged by the presence of intense charge-resonance transition in their optical spectra. Interestingly, these studies also discern that delocalization of a single cationic charge could occur over multiple fluorene rings in F2–F6, while the exciton is likely localized only onto two fluorenes in F2–F6. Facile synthesis of the D–spacer–A triads allowed us to demonstrate that efficient triplet energy transfer can occur through π-stacked polyfluorenes; the mechanism of energy transfer crosses over from tunneling to hopping with increasing number of fluorenes in the polyfluorene spacer. We suggest that the development of rigidly held π-stacked polyfluorenes, described herein, with well-defined redox and optoelectronic properties provides an ideal scaffold for the study of electron and energy transfer in D-spacer-A triads, where the Fn spacers serve as models for cofacially stacked π-systems.

We have designed and synthesized electron-rich calixarene derivatives, which undergo reversible electrochemical oxidation in a well-accessible potential range that allows the ready preparation and isolation of the corresponding cation radicals. Preparation of mono- or tetra-radical cation can be achieved by using stable aromatic cation-radical salts such as MA^+•, MB^+•, and NAP^+• as selective organic oxidants. The cation radicals of calixarenes are stable indefinitely at ambient temperatures and can be readily characterized by UV-vis-NIR spectroscopy. These cation radicals bind a single molecule of nitric oxide within its cavity with remarkable efficiency.

We employed the density functionaly theory (DFT)-predicted regioselectivity of the intramolecular Scholl reaction in phenanthrene and dibenzo[g,p]chrysene frameworks to obtain π-extended mono and double [7]helicenes, respectively. The formation of these helical structures occurs despite the buildup of a large strain energy up to 30 kcal/mol compared with their most stable isomers. The twisted and strained structures were characterized and analyzed by experimental (NMR, UV–vis, emission, electrochemistry, and single-crystal X-ray diffraction) techniques and were further supported by DFT calculations.

Here, we report two series (denoted as meta and para) of π-extended dibenzo[g,p]chrysenes (DBCs) with different substituents (H, Me and OMe). These six novel compounds benefit from the presence of eight methyl groups on the sp³ bridges which improve the solubility and rigidify the extended phenylenes. Their optoelectronic properties were determined using electrochemistry and spectroscopic (UV-vis and emission) techniques and further confirmed by DFT calculations. The results showed that both the position and nature of substituents on the π-extended moieties exert significant effects on the optoelectronic properties and the charge delocalization mechanism. In addition, isomerism (meta and para) leads to different packings in the solid state structure; interestingly, the crystal structure of the hydrogen substituted para molecule showed a permanent three-dimensional porous structure.

Herein, we report the synthesis of two new series of angular (all-syn) ladder-type meta-[n]phenylenes (LMP, n = 3–8). One series contains keto groups at the termini bridges, denoted angular keto (AKn), the second contains alkyl groups at all bridge sp³ carbons, denoted angular alkyl (AAn). Their electronic and structural properties were delineated by a combination of electrochemistry and spectroscopic (UV-Vis and emission) methods and further supported by DFT calculations. Interestingly, experimental and DFT data show that changing the bridging group at the termini from alkyl (AAn) to keto (AKn) gives an increase in the first reduction potentials and LUMO energies, as the π-system is extended. Also, the charge (de)localization behavior is different for these two species; while the AAn compounds stablize charge with Robin-Day class III, the AKn compounds show a clear switch from class III to class II. In comparison with the linear analogues (LKn and LAn), DFT results reveal a shape independency of the charge (de)localization mechanism in acceptor–π-acceptor series (AKn/LKn).

We report a practical two-step approach for the synthesis of hybrid-bridge macrocyclic molecules that has been used to synthesize two novel oxy-alternate-bridged macrocyclic molecules, oxy-alternate cyclotetraveratrylene (^O-altCTTV) and oxy-alternate cyclohexaveratrylene (^O-altCHV). Electrochemistry, absorption spectroscopy, X-ray crystallography, and DFT calculations demonstrate that ^O-altCTTV acts as a redox-induced molecular actuator, as its switches from the open conformation in the neutral state to the closed conformation in the cation-radical state.

Background: The mitogen-activated protein kinases (MAPK) pathway is functionally generic and critical in maintaining physiological homeostasis and normal tissue development. This pathway is under tight regulation, which is in part mediated by dual-specific phosphatases (DUSPs), wherein they dephosphorylate serine, threonine and tyrosine residues of ERK family of proteins. DUSP5 is of high clinical interest because of mutations we identified in this protein in patients with vascular anomalies. Unlike other DUSPs, DUSP5 has unique specificity towards substrate pERK1/2. Using molecular docking and simulation strategies, we previously showed that DUSP5 has two pockets, which are utilized in a specific fashion to facilitate specificity towards catalysis of its substrate pERK1/2. Remarkably, most DUSPs share high similarity in their catalytic sites. Studying the catalytic domain of DUSP5 and identifying amino acid residues that are important for dephosphorylating pERK1/2, could be critical in developing small molecules for therapies targeting DUSP5. Results: In this study, we utilized computational modeling to identify and predict the importance of two conserved amino acid residues, H262 and S270 in the DUSP5 catalytic site. Modeling studies predicted that catalytic activity of DUSP5 would be altered if these critical conserved residues were mutated. We next generated independent Glutathione-S-Transferase (GST)-tagged full-length DUSP5 mutant proteins carrying specific mutations H262F and S270A in the phosphatase domain. Biochemical analysis was performed on these purified proteins, and consistent with our computational prediction, we observed altered enzyme activity kinetic profiles for both mutants with a synthetic small molecule substrate (pNPP) and the physiological relevant substrate (pERK) when compared to wild type GST-DUSP5 protein. Conclusion: Our molecular modeling and biochemical studies combined demonstrate that enzymatic activity of phosphatases can be manipulated by mutating specific conserved amino acid residues in the catalytic site (phosphatase domain). This strategy could facilitate generation of small molecules that will serve as agonist of DUSP5 activity.

An efficient and highly selective synthetic method toward the preparation of pillar[n]arenes (n = 5, 6) is reported, based upon a high solvent-dependent selectivity found in the condensation reaction between 1,4-dialkyloxybenzene and paraformaldehyde, involving methanesulfonic acid as catalyst. Pillar[6]arene (P6) is obtained as the major product when using chloroform as solvent, while in dichloromethane pillar[5]arene (P5) is the dominant product. Accordingly, a series of P5 and P6 have been selectively synthesized with excellent yield.