Computational Evidence of the Incipient Oxocarbenium Ion as a "Hidden Intermediate" During the Cyclization of Hydroxyenol Ether into Spiroketal Under Mild Acidic Condition.

The synthesis of spiroketals has gained attention because of their importance in chemical and biological reactions. Yet, the mechanistic investigation of mild acid-catalyzed spiroketalization remains elusive and less explored in the literature and speculated that such transformations may proceed through the oxocarbenium ion intermediate; however, the existence of such species in mild acid-catalyzed spiroketalization is not documented. The computational study has been performed at M06-2X/6-31+G(d) level to examine the kinetically controlled product formation for such reactions and the intrinsic reaction coordinates of 1 d suggest that the reaction proceeds via a "one-step, two-stage" mechanism with the formation of transient oxocarbenium as a "hidden intermediate" in the reaction. This study reveals that stereoelectronic interactions devoid the formation of stable oxocarbenium ion intermediate after the proton transfer transition state in the mild acid catalyzed spiroketalization process.

Tandem Michael-anti-Michael Addition-Mediated Orthogonal Strapping of Diynones: Regioselective Spirocyclopentannulation of Oxindoles and Pyrazolones and DFT Validation.

An efficient protocol involving the transformation of sequentially generated recursive anions from heterocyclic precursors to orthogonally strap diynones through one pot transition-metal-free spirocyclopentannulation has been devised, employing oxindoles and pyrazolones as prototypical platforms. Insights into these regioselective tandem Michael-anti-Michael processes have been gleaned through DFT calculations.

Cooperativity between the Substrate and Ligand in Palladium-Catalyzed Allylic Alkylation Using 1-Aryl-1-propynes.

A monoprotected amino acid Bz-Gly-OH assists in the allylic alkylation of a variety of ketones, ß-keto esters, aldehydes, etc., during enamine-palladium catalysis. Density functional theory calculations reveal that Bz-Gly-OH assists in the formation of an enamine that attacks the π-allylpalladium complex via an outer sphere mechanism. The preliminary result points to an asymmetric allylic alkylation under a new mode of bifunctional catalysis.

Exploiting the optical sensing of fluorophore-tagged DNA nucleobases on hexagonal BN and Al-doped BN sheets: a computational study.

Hexagonal boron nitride (h-BN) sheets possess high fluorescence quenching ability and high affinity towards DNA/RNA, and they can be used as a sensing platform for rapid detection. We report the absorption and emission properties of DNA nucleobases such as adenine (A), cytosine (C), guanine (G), and thymine (T) tagged with benzoxazole on h-BN and aluminium-doped h-BN (Al_hBN) sheets. The binding affinity of studied nucleobases on h-BN sheets at the M062X/6-31G* level of theory showed the following adsorption trend: G ≥ T ≥ A > C, which is in good agreement with the previous results. The calculated stability trend of nucleobases on the Al_hBN sheet follows as C > G > A > T at the same level of theory. The physically adsorbed behavior of nucleobases to h-BN sheets was confirmed by the non-covalent interactions (NCIs) and the total density of states (TDOS) plots. The NCI results indicated that van der Waals interactions contribute significantly to the adsorption of nucleobases on h-BN sheets. Atoms in molecules (AIM) calculations revealed the electrostatic interactions between nucleobases and the Al_hBN sheet. The quenching phenomenon of nucleobase-tagged fluorophores on h-BN and Al_hBN sheets was investigated by TD-DFT calculations using the same level of theory. The thymine-tagged fluorophore upon adsorption to the pristine h-BN sheet was found to be blue-shifted (∼43 nm); however, the guanine-tagged fluorophore with Al_hBN showed a remarkable difference from other nucleobase-tagged fluorophores in the absorption and emission spectrum. Guanine-tagged fluorophores showed a smaller blue shift (∼7 nm) in the absorption spectrum; however, it showed a larger red shift (∼55 nm) than the other nucleobase-tagged fluorophores on Al_hBN sheets and can be useful in recognizing a sequence-specific phenomenon as a fluorescent biosensor of DNA and RNA to ascertain the presence of such nucleobases.

Deciphering the mechanism of action of 5FDQD and the design of new neutral analogues for the FMN riboswitch: a well-tempered metadynamics simulation study.

The FMN riboswitch is a novel drug target for the design of new antibiotics, and efforts have been made to design new charged and uncharged ligands. Uncharged ligands have shown advantages of not requiring any transporter for intracellular transport or proteins for their phosphorylation. 5FDQD (5-(3-(4-fluorophenyl)butyl)-7,8-dimethylpyrido(3,4-b)quinoxaline-1,3(2H,5H)-dione) is a recently reported neutral ligand for the FMN riboswitch active against Clostridium difficile infection in mice. However, the crystal structure of the 5FDQD bound FMN riboswitch is not available, and the mechanism of ligand binding and triggering the function of the riboswitch is not well understood. We have examined 5FDQD for its binding affinity with the FMN riboswitch using the well-tempered metadynamics (WT-MtD) simulation technique. The crystal structure of the FMN riboswitch shows that the FMN interacts with the J4/5 region through the phosphate group with G62; however, the uncharged ligands take advantage of π-π stacking interactions with the same residue of the riboswitch observed from the WT-MtD simulation results. The simulation results show that the presence of fluorine on the phenyl ring in 5FDQD is important to enhance the binding affinity of the neutral ligands with the FMN riboswitch. The WT-MtD results showed that the 1,2-difluoro substitution on the phenyl ring in 5FDQD (FMN-difluoro2) and the 1,3 positions in the phenyl ring (FMN-difluoro1) showed weaker binding energy with the FMN riboswitch compared to 5FDQD. The substitution of another fluorine atom at the 5-position of the phenyl ring (FMN-trifluoro) showed a comparable binding affinity (∼-31.4 kcal mol-1) to 5FDQD. Electron-donating substitution on the phenyl ring such as the amino group also lowered the binding affinity (-28.8 kcal mol-1) with the riboswitch compared to 5FDQD. The computed results suggest that the position and nature of substitution in the phenyl ring of the uncharged ligands affect the overall binding and such a delicate balance is important to achieve superior binding affinity with the FMN riboswitch.

The mechanism of conversion of substituted glycals to chiral acenes via Diels-Alder reaction: a computational study.

Synthesis of linearly fused aromatic systems using a glycal-based diene with an aryne is a long-standing topic of interest in glycal chemistry. We have examined the mechanistic pathways for the transformation of substituted glycals to chiral fused aromatic cores via Diels-Alder (DA) reaction using the SMDACN-M06-2X/6-31G(d) level of theory. The DA reactions of E (1a) and Z (1a') forms of C-2 alkenyl glycal and an aryl glycal (1b) as a diene were examined with a benzyne intermediate generated as a dienophile. The computational results reveal that 1a and 1b can only be transformed into the fused aromatic cores by the base-catalyzed reaction because a [1,5] sigmatropic hydrogen shift is not feasible. The activation free energy barrier for the base-catalyzed proton abstraction process is 4.2 kcal mol-1 and there is almost no barrier for stereoisomeric 1a DA-complexes. The activation free energy barrier values for stereoisomeric 1b DA-complexes for the base-catalyzed proton abstraction process are 10.8 and 12.4 kcal mol-1. The appropriate orientation of glycal-ring-oxygen and hydrogen at the 5th position of Z (1a') forms of C-2 alkenyl glycal facilitates the [1,5] sigmatropic hydrogen shift; however, the base-catalyzed reaction is energetically more favored than the former case. The rate-determining step for 1a and 1a' is the ring-opening step (18.2 and 19.5 kcal mol-1 for the S-stereoisomer), whereas the DA adduct formation step is the rate-determining step for 1b (16.1 kcal mol-1 for the S-stereoisomer). The structural analysis reveals the formation of the preferred S-stereoisomer over the R-stereoisomer with the respective dienes.

Probing the bent bonds in cyclopropane systems for gas storage and separation process: A computational study.

The hydrogen, carbon dioxide, and carbon monoxide gas adsorption and storage capacity of lithium-decorated cyclopropane ring systems were examined with quantum chemical calculations at density functional theory, DFT M06-2X functional using 6-31G(d) and cc-pVDZ basis sets. To examine the reliability of M06-2X DFT functional, a few representative systems are also examined with complete basis set CBS-QB3 method and CCSD-aug-cc-pVTZ level of theory. The cyclopropane systems can bind to one Li+ ion; however, the corresponding the methylated systems can bind with two Li+ ions. The cyclopropane systems can adsorb six hydrogen molecules with an average binding energy of 3.8 kcal/mol. The binding free energy (ΔG) values suggest that the hydrogen adsorption process is feasible at 273.15 K. The calculation of desorption energies indicates the recyclable property of gas adsorbed complexes. The same number of CO2 and CO gas molecules can also be adsorbed with an average binding energy of -14.4 kcal/mol and -10.7 kcal/mol, respectively. The carbon dioxide showed ~3-4 kcal/mol better binding energy as compared to carbon monoxide and hence such designed systems can function as a potential candidate for the separation of these flue gas molecules. The nature of interactions in complexes was examined with atoms in molecules analysis revealed the electrostatic nature for the interaction of Li+ ion with cyclopropane rings. The chemical hardness and electrophilicity calculations showed that the gas adsorbed complexes are rigid and therefore robust as gas storage materials.

Estimation of bisulfate in edible plant foods, dog urine, and drugs: picomolar level detection and bio-imaging in living organisms.

In order to explore the properties of any species in solution, the actual, i.e. equilibrium concentration of the free species should be taken into account. Researchers have not paid attention to the deprotonation equilibrium between HSO4- and SO42- while probing bisulfate ion. In this study, we have addressed this concern and developed two zwitterions, CG (coumarin-integrated glycine) and CA (coumarin-integrated alanine), for the selective detection of HSO4- at a picomolar level (50 to 325 pM) with very high binding affinity (∼108 M-1) in pure water at physiological pH. The principle of HSO4- recognition was established via UV-vis and fluorescence techniques. DFT calculations suggested that the H-bonding interactions between the probes and HSO4- are the driving force for this unforeseen selectivity. The membrane penetration ability and nontoxicity of CG/CA enable them to function as staining agents in living brine shrimps and bacteria. The use of these probes for the estimation of HSO4- in various day-to-day edible foods and drugs along with urine samples is unprecedented. The significance and novelty of this study lies in the application and development of assays for estimating bisulfate in several real-world samples that are predominantly aqueous in nature, which are the first of their kind.

A new strategy to generate super and hyper acids with simple organic molecules exploiting σ-hole interaction.

Super and hyper acidity can be achieved using σ-hole non-covalent interactions with simple organic systems. The σ-hole interaction can stabilize the conjugate base of acids to such an extent that cyclopentadiene yields a ΔHacid of 256 kcal mol-1, which is ∼100 kcal mol-1 lower than the reported results. The hyper acidic value of 209.0 kcal mol-1 of organic acids has been achieved without electron-withdrawing substituents rather exploiting only σ-hole interaction. Remarkably, the 1st and 2nd acidity values (∼229 kcal mol-1) of comparable strength in the hyperacid range have been observed for the first time using DFT computations. The simple organic acids were predicted to reach the pKa values in the range of -7.3 to -7.8 in DMSO, which is remarkably lower than previous reports. These stable anions can be a potential candidate for application as an effective electrolyte in lithium-ion batteries.

Revealing the mechanistic pathway of cholinergic inhibition of Alzheimer's disease by donepezil: a metadynamics simulation study.

Donepezil, an acetylcholinesterase inhibitor, is an approved drug for the symptomatic treatment of Alzheimer's disease (AD). The mechanistic pathway for the inhibition mechanism of acetylcholinesterase (AChE) by donepezil is not well explored. We report for the first time, the inhibition mechanism of AChE by the donepezil drug molecule for the hydrolysis of acetylcholine (ACh) with docking and well-tempered metadynamics (WTMtD) simulations with a human acetylcholinesterase (hAChE) crystal structure (). This study explored the orientation of the donepezil drug molecule inside the gorge of AChE. The 1D free energy surface obtained from WTMtD simulation studies reveals that the orientation of donepezil in the crystal donepezil (-87.25 kJ mol-1) is energetically more favored than the other orientation of donepezil (-74.74 kJ mol-1) for inhibition of AChE. The free energy landscape computation for the two sets of CVs further corroborates the 1D free energy surface. The WTMtD simulation performed with the crystal structure of donepezil bound hAChE gives the conformation of donepezil at Basin-I as similar to the conformation of donepezil observed in the crystal structure (). The WTMtD simulations further reveal that the bridged water molecules are more ordered near the catalytic triad of AChE to deter the nucleophilicity of Ser203 through intermolecular hydrogen bonding when donepezil approaches near to the active site gorge of AChE. The presence of donepezil near the active site of AChE can inhibit its approach for ACh hydrolysis; this is revealed through the docking study, where the drug molecule inside the active gorge of hAChE restricts the approach of ACh to Ser203 for the hydrolysis process.

Instant Detection of Hydrogen Cyanide Gas and Cyanide Salts in Solid Matrices and Water by using CuII and NiII Complexes of Intramolecularly Hydrogen Bonded Zwitterions.

A series of intramolecularly hydrogen-bonded zwitterionic compartmental ligands HL1-HL4, containing a pendent diamine arm that is monoprotonated and an aldehyde functionality at two different ortho-positions of a 4-halophenoxide, is reported herein. Single-crystal X-ray diffraction (SXRD) provides persuasive evidence for the identification of this class of proton-transferred zwitterions at room temperature. The solid-state photoluminescent nature of these zwitterions remains intact in aqueous and organic solutions. Grinding of HL1 and HL2 with Cu2+ /Ni2+ salts develop turn-on probes 1-4. Compounds 1 and 4 are dinuclear CuII and NiII species, respectively. Compound 2 is a tetranuclear CuII complex. Interestingly, compound 3 is a mononuclear NiII species in which both nitrogen atoms in the pendant diamine arm are protonated and, therefore, not coordinated to the NiII center. All these probes (1-4) display an instant response to the poison gas hydrogen cyanide (HCN) and cyanide salts present in both solid matrices and aqueous (100 % water) solution. Selective and rapid sensing of HCN gas and cyanide salts in solid/soil/water phases, without any interference, by the mechanosynthesized complexes 1-4 can be perceived easily by the naked eye under a hand-held UV lamp.

Impact of "half-crown/two carbonyl"-Ca2+ metal ion interactions of a low molecular weight gelator (LMWG) on its fiber to nanosphere morphology transformation with a gel-to-sol phase transition.

We report here a smart functional low molecular weight gelator (LMWG) L, containing an unusual metal ion coordination site, i.e. "half-crown/two carbonyl". The gelator L shows excellent gelation behavior with typical fibrillar morphology in acetonitrile, methanol and ethanol media. Upon Ca2+ ion binding with its "half-crown/two carbonyl" coordination site, the acetonitrile gel of L exhibits a fiber to nanosphere morphology transformation along with a gel-to-sol phase transition as confirmed by microscopic investigation and by direct naked eye visualization, respectively. The mechanism involved in this morphology transformation and gel-to-sol phase transition process was studied thoroughly with the help of computational calculations and various spectroscopic experiments and discussed.

Influence of gauche effect on uncharged oxime reactivators for the reactivation of tabun-inhibited AChE: quantum chemical and steered molecular dynamics studies.

The neutral oxime reactivator RS194B with a seven-membered ring has shown better efficacy towards the tabun-inhibited AChE than that of RS69N with a six-membered ring and RS41A with a five-membered ring. The difference in the efficacy of these reactivators has remained unexplored. We report here the origin of the difference of efficacy of these reactivators based on the conformational analysis, quantum chemical calculations and steered molecular dynamics (SMD) simulations. The conformational analysis using B3LYP/6-31G(d) level of theory revealed that RS41A and RS194B are more stable in gauche conformation due to the gauche effect (-N-C-C-N- bonds) whereas RS69N prefers anti-conformation. The SMD simulations show that RS194B retains in more stable gauche conformation inside the active gorge of AChE during different time intervals that experiences more hydrogen bonding, hydrophobic interactions with the catalytic anionic site (CAS) residues and weaker interactions with the peripheral anionic site (PAS) residues compared to RS41A and RS69N. In an effort to design an even superior reactivator, RS194B-S has been chosen with a subtle change in the geometry of RS194B by replacing the carbonyl oxygen with the sulfur atom. The newly designed reactivator RS194B-S can also be a promising candidate to reactivate tabun-inhibited AChE.

DFT studies on quantum mechanical tunneling in tautomerization of three-membered rings.

We have examined keto-enol and amino-imino tautomerization in a set of three-membered ring systems (1-5) in the absence and presence of water molecules. Aromaticity governs the keto-enol and amino-imino tautomerization processes in (1-5), which lead to the formation of enol and imine derivatives. The possibility of quantum mechanical tunneling (QMT) has not been reported in the tautomerization processes of three-membered ring systems. M062X/6-311+G(d,p) level of theory QMT calculations reveal that tunneling is not possible in the water unassisted processes because of very high free energy activation barriers. The activation free energy barriers for the amino-imino tautomerization of 5, aziridine-2,3-diimine, and one water assisted, 5-W, are 58.1 kcal mol-1 and 14.8 kcal mol-1, respectively and the lowest among the 3-membered rings examined. The classical over the barrier rate constant (kCVT) obtained by QMT calculation for 5-W→5-W-P is 10.6 s-1 at 273 K. Inclusion of small curvature tunneling (SCT) enhances the classical over the barrier rate constant by 15.1 times at 273 K, i.e., kCVT+SCT is 160 s-1 and reveals nonclassical behaviour for the tautomerization of 5-W. A higher kinetic isotope effect in the tautomerization process of 4-W and 5-W also indicates a pronounced contribution of tunneling toward the tautomerization process. The two-water assisted tautomerization of 3 has the highest activation free energy barrier in the series indicating a nonclassical contribution to 3-2W→3-2W-P. These results suggest that the tautomerization processes of 1-5 are experimentally feasible by tunneling and aromaticity.

Computational predictions turning the isomers of alanine to generate distinct morphs of free-flowing salt crystals.

The morphology of salt crystals has been an active area of research for decades and remains largely empirical. This study reveals the computational modeling guides to arrive at the correct answer, even for complex problems, such as the morphology of salt crystals with additives. There is no report on the two different morphologies of rock-salt crystals with two isomers of a single additive. Alanine isomers (α- and ß-) can induce octahedron and rhombic dodecahedron morphologies in salt crystals. The computational study demonstrated that α-alanine preferentially interacts with {111} and ß-alanine with {110} planes to yield such morphologies. The change in morphology with alanine can greatly influence the problem of the free-flowing issue of salt crystals.

Revealing Germylene Compounds to Attain Superbasicity with Sigma Donor Substituents: A Density Functional Theory Study.

Compounds of GeII are shown for the first time to function as superbases. Two B(N=PiPr3 )2 groups attached to a germanium(II) center show a gas-phase proton affinity of 296.2 kcal mol-1 , which is close to the range of a hyperbase as revealed by B3LYP-D3/6-31G(2d,p) level of theory. These DFT calculations showed better agreement of geometrical parameters for the reported stable germylene compound 1 than previously reported calculations. A systematic study with different substitutions of GeII revealed that such a system can achieve basicity close to a hyperbase. The stabilities of these superbases were examined with dimerization energy and singlet-triplet state energy difference (ΔES-T ). Furthermore, the calculated gas-phase proton affinity values also show good correlation with the most negative valued point (Vmin ) in electron-rich regions from the molecular electrostatic potential. The high PA values of compounds were also supported by ionization potential, electron affinity, absolute electronegativity, and absolute hardness calculations. The energetics for the reaction with BH3 and AlMe3 further suggest that the lone pair of GeII can act as a Lewis base and display higher donor-acceptor bond strengths.

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.

Revealing the importance of linkers in K-series oxime reactivators for tabun-inhibited AChE using quantum chemical, docking and SMD studies.

Inhibition of acetylcholinesterase (AChE) with organophosphorus compounds has a detrimental effect on human life. Oxime K203 seems to be one of the promising reactivators for tabun-inhibited AChE than (K027, K127, and K628). These reactivators differ only in the linker units between the two pyridinium rings. The conformational analyses performed with quantum chemical RHF/6-31G* level for K027, K127, K203 and K628 showed that the minimum energy conformers have different orientations of the active and peripheral pyridinium rings for these reactivator molecules. K203 with (-CH2-CH=CH-CH2-) linker unit possesses more open conformation compared to the other reactivators. Such orientation of K203 experiences favorable interaction with the surrounding residues of catalytic anionic site (CAS) and peripheral anionic site (PAS) of tabun-inhibited AChE. From the steered molecular dynamics simulations, it has been observed that the oxygen atom of the oxime group of K203 reactivator approaches nearest to the P-atom of the SUN203 (3.75 Å) at lower time scales (less than ~1000 ps) as compared to the other reactivators. K203 experiences less number of hydrophobic interaction with the PAS residues which is suggested to be an important factor for the efficient reactivation process. In addition, K203 crates large number of H-bonding with CAS residues SUN203, Phe295, Tyr337, Phe338 and His447. K203 barely changes its conformation during the SMD simulation process and hence the energy penalty to adopt any other conformation is minimal in this case as compared to the other reactivators. The molecular mechanics and Poisson-Boltzmann surface area binding energies obtained for the interaction of K203 inside the gorge of tabun inhibited AChE is substantially higher (-290.2 kcal/mol) than the corresponding K628 reactivator (-260.4 kcal/mol), which also possess unsaturated aromatic linker unit.

Exploiting hydrogen bonding interactions to probe smaller linear and cyclic diamines binding to G-quadruplexes: a DFT and molecular dynamics study.

G-quadruplexes are formed by the association of four guanine bases through Hoogsteen hydrogen bonding in guanine-rich sequences of DNA and exist in the telomere as well as in promoter regions of certain oncogenes. The sequences of G-quadruplex-DNA are targets for the design of molecules that can bind and can be developed as anti-cancer drugs. The linear and cyclic protonated diamines have been explored to bind to G-quadruplex-DNA through hydrogen bonding interactions. The quadruplex-DNA binders exploit π-stacking and hydrogen bonding interactions with the phosphate backbone of loops and grooves. In this study, linear and cyclic protonated diamines showed remarkable binding affinity for G-tetrads using hydrogen bonding interactions. The DFT M06-2X/6-31G(d)//B3LYP/6-31+G(d) level of theory showed that the cyclic ee-1,2-CHDA (equatorial-equatorial form of 1,2-disubstituted cyclohexadiamine di-cation) binds to the G-tetrads very strongly (∼70.0 kcal mol-1), with a much higher binding energy than the linear protonated diamines. The binding affinity of ligands for G-tetrads with counterions has also been examined. The binding preference of these small ligands for G-tetrads is higher than for DNA-duplex. The binding affinity of an intercalated acridine-based ligand (BRACO-19) for G-quadruplexes has been examined and the binding energy is relatively lower than that for the 1,2 disubstituted cyclohexadiamine di-cation with G-tetrads. The atoms-in-molecules (AIM) analysis reveals that the hydrogen bonding interactions between the organic systems with G-tetrads are primarily electrostatic in nature. The molecular dynamics simulations performed using a classical force field (GROMACS) also supported the phosphate backbone sites of G-quadruplex-DNA to bind to these diamines. To mimic the structural pattern of BRACO-19, the designed inhibitor N,2-bis-2(3,4-aminocyclohexyl) acetamide (9) examined possesses two 1,2-CHDA moieties linked through an acetamide group. The molecular dynamics results showed that the designed molecule 9 can efficiently bind to the base-pairs and the phosphate backbone of G quadruplex-DNA using H-bonding interactions. The binding affinity calculated for the intercalated acridine-based drug (BRACO-19) with G-quadruplexes is weaker compared to ee-1,2-CHDA. These ligands deliver a different binding motif (hydrogen bonding) compared to the reported G-quadruplex binders of π-delocalized systems and will kindle interest in examining such scaffolds to stabilize DNA.

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.