Experimental and Computational Study of the ( Z)-Selective Formation of Trisubstituted Olefins and Benzo-Fused Oxacycles from the Ruthenium-Catalyzed Dehydrative C-H Coupling of Phenols with Ketones.

The cationic Ru-H complex was found to be an effective catalyst for the dehydrative C-H coupling of phenols with ketones to form the trisubstituted olefin products. The coupling of phenol with linear ketones led to highly stereoselective formation of the ( Z)-olefin products. The dehydrative coupling of phenol with enones and diones efficiently formed the benzopyrene and related oxacyclic derivatives. The reaction of 3,5-dimethoxyphenol with cyclohexanone-2,2,6,6- d4 showed a significant H/D exchange to both vinyl and α-CH2 positions on the olefin product (72-75% D). A significant carbon isotope effect was observed on the ortho-arene carbon of the olefin product. The free energies of intermediate species for the entire catalytic cycle were successfully computed by using the DFT method. The DFT study revealed that the E/ Z stereoselectivity is a result of the energy difference in the insertion step of ortho-metalated phenol to an enol form of the ketone substrate (ΔΔ E = 9.6 kcal/mol). The coupling method provides a direct catalytic C-H olefination method for ketones to form trisubstituted olefins without employing any reactive reagents or forming any wasteful byproducts.

α-Amino Acid Derived Benzimidazole-Linked Rhodamines: A Case of Substitution Effect at the Amino Acid Site toward Spiro Ring Opening for Selective Sensing of Al3+ Ions.

α-Amino acid derived benzimidazole-linked rhodamines have been synthesized, and their metal ion sensing properties have been evaluated. Experimentally, l-valine- and l-phenylglycine-derived benzimidazole-based rhodamines 1 and 2 selectively recognize Al3+ ion in aqueous CH3CN (CH3CN/H2O 4/1 v/v, 10 mM tris HCl buffer, pH 7.0) over the other cations by exhibiting color and "turn-on" emission changes. In contrast, glycine-derived benzimidazole 3 remains silent in the recognition event and emphasizes the role of α-substitution of amino acid undertaken in the design. The fact has been addressed on the basis of the single-crystal X-ray structures and theoretical calculations. Moreover, pink 1·Al3+ and 2·Al3+ ensembles selectively sensed F- ions over other halides through a discharge of color. Importantly, compounds 1 and 2 are cell permeable and have been used as imaging reagents for the detection of Al3+ uptake in human lung carcinoma cell line A549.

A Switch-On NIR Probe for Specific Detection of Hg2+ Ion in Aqueous Medium and in Mitochondria.

A new 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based probe molecule (L) is synthesized for specific binding to Hg2+ ion in physiological condition with an associated luminescence ON response in the near-IR region of the spectrum. Appropriate functionalization in the 5-position of each of two pyrrole moieties with styryl functionality in a BODIPY core helped us in achieving the extended conjugation and a facile intramolecular charge transfer transition with a narrow energy gap for frontier orbitals. This accounted for a poor emission quantum yield for the probe molecule L. Binding to Hg2+ helped in interrupting the facile intramolecular charge transfer (ICT) process that was initially operational for L. This resulted in a hypsochromic shift of absorption band and a turn-on luminescence response with λMaxEms of 650 nm on specific binding to Hg2+. Observed spectral changes are rationalized based on quantum chemical calculations. Interestingly, this reagent is found to be localized preferentially in the mitochondria of the live human colon cancer (Hct116) cells. Mitochondria is one of the major targets for localization of Hg2+, which actually decreases the mitochondrial membrane potential and modifies various proteins having sulfudryl functionality(ies) to cause cell apoptosis. Considering these, ability of the present reagent to specifically recognize Hg2+ in the mitochondrial region of the live Hct116 cells has significance.

Regioselectivity of vinyl sulfone based 1,3-dipolar cycloaddition reactions with sugar azides by computational and experimental studies.

DFT (M06-L) calculations on the transition state for the 1,3-dipolar cycloadditions between substituted vinyl sulfones with sugar azide have been reported in conjunction with new experimental results, and the origin of reversal of regioselectivity has been revealed using a distortion/interaction model. This study provides the scientific justification for combining organic azides with two different types of vinyl sulfones for the preparation of 1,5-disubstituted 1,2,3-triazoles and 1,4-disubstituted triazolyl esters under metal-free conditions.

Oxazoline-based organocatalyst for enantioselective strecker reactions: a protocol for the synthesis of levamisole.

A chiral oxazoline-based organocatalyst has been found to efficiently catalyze asymmetric Strecker reactions of various aromatic and aliphatic N-benzhydrylimines with trimethylsilyl cyanide (TMSCN) as a cyanide source at -20 °C to give α-aminonitriles in high yield (96 %) with excellent chiral induction (up to 98 % ee). DFT calculations have been performed to rationalize the enantioselective formation of the product with the organocatalyst in these reactions. The organocatalyst has been characterized by single-crystal X-ray diffraction analysis, as well as by other analytical methods. This protocol has been extended to the synthesis of the pharmaceutically important drug molecule levamisole in high yield and with high enantioselectivity.

In silico studies toward understanding the interactions of DNA base pairs with protonated linear/cyclic diamines.

Protonated amino groups are ubiquitous in nature and important in the fields of chemistry and biology. In search of efficient polyamine analogues, we have performed DFT calculations on the interactions of some simple cyclic and constrained protonated diamines with the DNA base pairs and compared the results with those obtained for the corresponding interactions involving linear diamines, which mimic biogenic polyamines such as spermine. The interactions are mainly governed by the strong hydrogen bonding between the ligand and the DNA base pairs. The DFT calculations suggest that the major-groove N7 interaction (GC base pair) with linear diamine is energetically more favored than other possible interactions, as reported with spermine. The cyclic diamines exhibited better interactions with the N7 site of the AT and GC base pairs of DNA than the linear diamines. The net atomic charges calculated for the protonated amine hydrogens were higher for the cyclic systems than for the linear diamines, inducing better binding affinity with the DNA base pairs. The stable conformers of cyclic diamines were predicted using the MP2/aug-cc-pVDZ level of theory. The positions of the protonated diamine groups in these cyclic systems are crucial for effective binding with the DNA base pairs. The DFT-calculated results show that diequatorial (ee) 1,2-cyclohexadiamine (CHDA) is a promising candidate as a polyamine analogue for biogenic polyamines. Molecular dynamics simulations were performed using explicit water molecules for the interaction of representative ligands with the DNA base pairs to examine the influence of solvent molecules on such interactions.

Synthetically amenable amide derivatives of tosylated-amino acids as organocatalysts for enantioselective allylation of aldehydes: computational rationale for enantioselectivity.

A phenylalanine derived chiral amide is developed that serves as an effective organocatalyst for the reaction of allyltrichlorosilane with aryl, hetero-aryl and α,ß-unsaturated aldehydes to afford the desired homoallylic alcohols in good yield (up to 90%) and high enantioselectivity (up to 99%). The experimental results and DFT calculations suggest that para substituted aromatic aldehydes as substrate show higher ee in the product than their ortho/meta counterparts. The (1)H and (13)C NMR spectra study corroborated the calculated results. The chiral organocatalyst can be easily synthesized from optically pure phenylalanine in two simple steps with 90% overall yield.