Deciphering the shape selective conformational equilibrium of E- and Z-locked azobenzene-tetraethylammonium ion in regulating photo-switchable K+-ion channel blocking.

The search for photo-switchable optopharmacological agents that can block ion channels has been a prevalent area owing to its prime advantages of reversibility and specificity over the traditional blockers. However, the quest for a higher blocking ability shown by a less stable photo-isomer to perfectly suit the requirement of the optopharmacological agents is still ongoing. To date, only a marginal improvement in terms of blocking ability is observed by the less stable E-isomer of para-substituted locked azobenzene with TEA (LAB-TEA) for the K+-ion channel. Thus, rationalization of the limitation for achieving high activity by the E-isomer is rather essential to aid the improvement of the efficiency of photoswitchable blocker drugs. Herein, we report a molecular-level analysis on the mechanism of blocking by E- and Z-LAB-TEA with the bacterial KcsA K+-ion channel using Molecular Dynamics (MD) simulation and Quantum Mechanical (QM) calculations. The positively charged TEA fragment engages in stronger electrostatic interactions, while the neutral LAB fragment engages in weaker dispersive interactions. The binding free energy calculated by Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) for E-LAB-TEA (-22.3 kcal mol-1) shows less thermodynamic preference for binding with K+-ion channels than Z-LAB-TEA (-21.6 kcal mol-1) corroborating the experimental observation. The correlation between the structure and the binding ability of E- and Z-isomers of LAB-TEA indicates that the channel gate is narrow and acts as a bottleneck for the entry of the binder molecule inside the large cavity. Upon irradiation, the Z-isomer converts into a less stable but long and planar E-isomer (ΔE of photoisomerism = 7.0 kcal mol-1, at SA2-CASPT2(6,4)/6-31+G(d)//CASSCF(6,4)/6-31+G(d)), which is structurally more suitable to fit into the narrow channel gate rather than the curved and non-planar Z-LAB-TEA. Thus, a reduction in the ionic current is observed owing to the preferential entry and subsequent blocking by E-LAB-TEA. Discontinuing the irradiation leads to conversion to the Z-isomer, the curved nature of which hinders its spontaneous release outside the cavity, thereby contributing only a small increase in the ionic current.

Hydrogen Evolution Activity of Nitrogen-Rich g-C3-xN4+x Synthesized by Solid-Gas Interface Method.

Synthesis of a metal-free carbon nitride (g-C3N4) photocatalyst in the form of nitrogen-rich g-C3-xN4+x derivatives is desirable for efficient solar to hydrogen conversion and remains a challenging task to achieve. Herein we report the development of homogeneous sheets of nitrogen-rich graphitic carbon nitride samples from melamine by a solid-gas interface approach. Using this method, pure g-C3N4 (CN), g-C3-xN4+x under ammonia flow (CN-NH3) and g-C3-xN4+x under nitrogen flow (CN-N2) are prepared. The g-C3-xN4+x (CN-NH3) sample shows better surface conductivity, wide optical absorbance in the visible region, reduced recombination and high electron donor density, and higher performance toward photoelectrochemical hydrogen evolution (HER). The g-C3-xN4+x (CN-NH3) generates a photocurrent of 2.06 µA cm-2, which is 2.5 times higher than that of the pure g-C3N4 (CN) sample (0.85 µA cm-2). It also shows higher photocatalytic water splitting ability compared to the CN and CN-N2 samples, generating 634 µmol g-1 hydrogen without cocatalyst and 1163 µmol g-1 of hydrogen with Pt cocatalyst. Density functional calculations suggest that the progressive band gap reduction with the increase in the N-dopant percentage can be attributed to the gradual increase in the partial π-occupations, which can lead to a significant stabilization of the conduction band minima. The theoretical modeling, however, indicates a saturation in the band gap effect after 75% of N-dopant. The onset potential of g-C3-xN4+x for HER appears at η = 0.43 V in dark and η = 0.34 V vs Ag/AgCl under solar light illumination of 1 sun.

Molecular mechanism of Be2+-ion binding to HLA-DP2: tetrahedral coordination, conformational changes and multi-ion binding.

The chemistry of beryllium is rather unusual, however, less explored as compared to other main group elements. This is mainly attributed to the high toxicity of beryllium, leading to chronic granulomatous pneumonitis, called chronic beryllium disease (CBD). It has been reported that Be2+-ion binding to the human leukocyte antigen protein (HLA-DP2) and peptide (M2) results in favorable interaction with the T-cell receptor protein (TCR), which initiates immune-mediated toxicity. We have carried out molecular dynamics (MD) simulations combined with quantum mechanical/molecular mechanical (QM/MM) studies to explore the binding nature of Be2+ with a HLA-DP2 protein and M2 peptide. The interaction between the negatively charged M2 peptide and the negatively charged binding cleft of HLA-DP2 is unfavorable. However, this interaction is stabilized by one Be2+ and two Na+-ions bridged by negatively charged carboxyl groups of glutamate residues (ß26E and ß69E) of the ß-chain of HLA-DP2 and one glutamate (p7E) and one aspartate residue (p4D) of the M2 peptide. This multi-ion cavity consists of tetrahedrally coordinated static Be2+ and Na+-ions, as well as one dynamically exchangeable Na+-ion. The smaller size and higher charge of the Be2+-ion as compared to the Na+-ion reduce the distance between the M2 peptide and the ß-chain of HLA-DP2, which results in conformational change suitable for TCR binding. However, the replacement of the Be2+ by the Na+-ion could not generate a suitable binding site for TCR.

Different Donor-Acceptor Interactions of Carbene Ligands in Heteroleptic Divalent Group 14 Compounds, LEL' (E=C-Sn; L=N-Heterocyclic Carbene; L'=Cyclic Alkyl(Amino) Carbene).

The electronic structure and reactivity of heteroleptic divalent group 14 compounds, 1E (E=C-Sn) with NHC and cAAC ligands have been studied at the BP86/TZ2P level of theory and compared with homoleptic group 14 compounds. The EDA-NOCV (energy decomposition analysis-natural orbitals for chemical valence) analysis indicates that the interaction between the two carbene ligands and the central C-atom in 1C can be best represented as one 3c-2e electron sharing σ-bond and one 3c-2e donor-acceptor σ-bond. There exists an electron sharing interaction between the π-type orbital on the central C-atom and the C-N π* orbital of cAAC and a π-back-donation from the σ-type lone pair on the central C-atom to the π*-MO of NHC. This bonding description is equivalent to the localized bonding representation, where the central C-atom forms two electron sharing bonds and two donor-acceptor bonds with cAAC and NHC ligands. However, the bonding between the carbene ligands and the heavier group 14 element can be best represented as two 2c-2e donor-acceptor σ-bonds and a π-back-donation from group 14 element to C-N π* orbital of cAAC. This bonding description is well supported by the geometrical and Natural Bond Orbital (NBO) analyses. Hence, 1C can be best described as a carbene and the heavier analogues can be best described as tetrylones. However, the high first (287.6-274.3 kcal mol-1 ) and second proton affinities (162.0-158.5 kcal mol-1 ) suggest that 1E (E=C-Sn) behave as tetrylones.

Roles of different amino-acid residues towards binding and selective transport of K+ through KcsA K+-ion channel.

The roles of different amino acid residues towards binding and selective transport of K+ ion in the selectivity filter of the bacterial K+ ion channel, KcsA, were explored. The selectivity filter of KcsA contains amino acids threonine (THR-75), valine (VAL-76), glycine (GLY-77) and tyrosine (TYR-78) from intracellular to extracellular regions. The hydroxyl-hydrogen and carbonyl-oxygen of THR-75 situated at the intracellular region are engaged in intra-residue hydrogen bonding. Thus, the hydroxyl-oxygens orient away from and the hydroxyl-hydrogens orient towards the center of the selectivity filter. Hence, this site attracts and acts as a 'gate' for the incoming K+ ion. The binding of K+ ion is first observed with eight carbonyl-oxygens of THR-75 and VAL-76 (S3 site). However, binding at this site breaks the intra-residue hydrogen bonding of THR-75, which in turn reorients the hydroxyl-hydrogens away from the selectivity filter. Accordingly, binding of K+ ion at this site prevents the instantaneous approach of another K+ ion. Thus, VAL-76 acts as a 'hinge' to open and close the 'gate'. The next amino acid, GLY-77, shows low affinity towards K+ ion, thus acting as a 'regulator'. TYR-78 situated at the extracellular region shows strong binding affinity towards K+ ion, and thus assists in the transport of K+ ion from the intracellular to the extracellular region. The release of K+ ion to form hydrated K(H2O)8+ in the extracellular region is endothermic (4.9 kcal mol-1). Hence, the process of K+ ion transport is likely to be kinetically controlled. Moreover, the highest binding energy of Na+ is observed at the center of four carbonyl-oxygens of VAL-76 (-68.8 kcal mol-1), which is even higher than the highest binding energy of K+ ion at S3 (-63.9 kcal mol-1). Na+ binding energy decreases from intracellular to extracellular region. Hence, intracellular Na+ ion would block the passage of K+ ion. The K+ ion concentration is high in the intracellular region, and it moves from intracellular to extracellular region, while Na+ ion concentration is high in the extracellular region, and it moves from extracellular to intracellular region. Thus, the selective transport of K+/Na+ ion in KcsA can be attributed to the competition between K+ ion exit and Na+ ion entry at the center of four carbonyl-oxygens of TYR-78.

Effect of Transition Metal Fragments on the Reverse Fritsch-Buttenberg-Wiechell Type Ring Contraction Reaction of Metallabenzynes to Metal-Carbene Complexes.

Metallabenzynes (1M), contrary to their organic analogues, benzynes, undergo ring-contraction to metal-carbene complexes (2M) via a reverse Fritsch-Buttenberg-Wiechell (FBW) type rearrangement. A detailed computational quantum mechanical study has been carried out to understand the effect of different third row transition metal fragments (ML2L'2; M = W, Re, Os, Ir, Pt; L/L' = PH3, Cl, CO) on the stability of metallabenzynes and their reactivity toward reverse FBW type rearrangement. Our results indicate that the late transition metal fragments Ir(PH3)Cl3 and PtCl4 prefer 16 VE metal-carbene complex (2M), while the middle transition metal fragments W(PH3)4, Re(PH3)3Cl, and Os(PH3)2Cl2 prefer metallabenzyne (1M). This can be attributed to the reduced overlap between the transition metal fragment ML2L'2 and organic fragment C5H4 in metallabenzyne 1M when M changes from W to Pt. Furthermore, the presence of a π-accepting ligand CO on the metal fragment makes the conversion of 1M to 2M more feasible.

Trapping a Silicon(I) Radical with Carbenes: A Cationic cAAC-Silicon(I) Radical and an NHC-Parent-Silyliumylidene Cation.

The trapping of a silicon(I) radical with N-heterocyclic carbenes is described. The reaction of the cyclic (alkyl)(amino) carbene [cAACMe ] (cAACMe =:C(CMe2 )2 (CH2 )NAr, Ar=2,6-iPr2 C6 H3 ) with H2 SiI2 in a 3:1 molar ratio in DME afforded a mixture of the separated ion pair [(cAACMe )2 Si:. ]+ I- (1), which features a cationic cAAC-silicon(I) radical, and [cAACMe -H]+ I- . In addition, the reaction of the NHC-iodosilicon(I) dimer [IAr (I)Si:]2 (IAr =:C{N(Ar)CH}2 ) with 4 equiv of IMe (:C{N(Me)CMe}2 ), which proceeded through the formation of a silicon(I) radical intermediate, afforded [(IMe )2 SiH]+ I- (2) comprising the first NHC-parent-silyliumylidene cation. Its further reaction with fluorobenzene afforded the CAr -H bond activation product [1-F-2-IMe -C6 H4 ]+ I- (3). The isolation of 2 and 3 confirmed the reaction mechanism for the formation of 1. Compounds 1-3 were analyzed by EPR and NMR spectroscopy, DFT calculations, and X-ray crystallography.

An Aluminum Dihydride Working as a Catalyst in Hydroboration and Dehydrocoupling.

The well-defined aluminum dihydride LAlH2 (L = HC(CMeNAr)2, Ar = 2,6-Et2C6H3) (1) operates in catalysis like a transition metal complex. The catalytic activity of 1 for hydroboration of terminal alkynes was investigated. Furthermore, catalyst 1 effectively initiated the dehydrocoupling of boranes with amines, thiols, and phenols, respectively, to form compounds with B-E bonds (E = N, S, O) under elimination of H2. Quantum mechanical calculations indicate that hydroboration and dehydrocoupling reactions occur via three consecutive cycloaddition reactions involving the activation of the X-H (X = Al, B, C, and O) σ-bonds.

Synthesis of a Bent 2-Silaallene with a Perturbed Electronic Structure from a Cyclic Alkyl(amino) Carbene-Diiodosilylene.

The cyclic alkyl(amino) carbene (cAAC) 1 reacted with SiI4 in toluene, affording the cAAC-silicon tetraiodide complex [(cAACMe)SiI4] (2, cAACMe = :C(CH2)(CMe2)2NAr, Ar = 2,6-iPr2C6H3). It further reacted with two equivalents of KC8 in toluene at room temperature to afford the first cAAC-diiodosilylene [(cAACMe)SiI2] (3). DFT calculations show that the Ccarbene-Si bond in 3 is formed by the donation of the lone pair of electrons on the Ccarbene atom to the SiI2 moiety, while the π-back-bonding of the lone pair of electrons on the Si atom to the Ccarbene atom is negligible. The presence of the lone pair of electrons on the silicon atom in 3 is also evidenced by its reaction with N3SiMe3 to form the cAAC-silaimine complex [(cAACMe)Si(NSiMe3)I2] (4). Compound 3 reacted with IiPrMe (:C{N(iPr)CMe}2) in n-hexane to form the NHC-cAAC-silyliumylidene iodide [cAACMe(SiI)IiPrMe]I (5), which was then reacted with two equivalents of KC8 in toluene to furnish [cAACMeSi(IiPrMe)] (6). The experimental and theoretical studies suggest that 6 can be described as a bent silaallene with a perturbed electronic structure, which can be attributed to the different donor-acceptor properties of cAACMe and IiPrMe. Compounds 3-6 were elucidated by NMR spectroscopy, X-ray crystallography, and theoretical studies.

Multiple Cycloaddition Reactions of Ketones with a ß-Diketiminate Al Compound.

A ß-diketiminate Al compound (1) with an exocyclic double bond reacts with two equivalents each of benzophenone and 2-benzoylpyridine in a [4+2] cycloaddition to generate bicyclic and tricyclic compounds 2 and 3, respectively. Compound 2 consists of six- and eight-membered aluminium rings, whereas 3 has two five- and one eight-membered ring. Compounds 2 and 3 were characterized by a number of analytical tools including single-crystal X-ray diffraction. The quantum mechanical calculations suggest that the dissociation of the solvent molecule from 1 would lead to an active species 1A having two 1,4-dipolar 4π electron moieties, in which the electrophilic site is the Al atom and the nucleophilic positions are polarized exocyclic and endocyclic C=C π bonds. The detailed mechanistic study shows that the dipolarophiles, benzophenone, and 2-benzoylpyridine undergo double cycloaddition with two 1,4-dipolar 4π electron moieties of 1A. Herein, the addition of one molecule of the dipolarophile promotes the addition of the second one.

An Aluminum Hydride That Functions like a Transition-Metal Catalyst.

The reaction of [LAlH2 ] (L=HC(CMeNAr)2 , Ar=2,6-iPr2 C6 H3 ) with MeOTf (Tf=SO2 CF3 ) resulted in the formation of [LAlH(OTf)] (1) in high yield. The triflate substituent in 1 increases the positive charge at the aluminum center, which implies that 1 has a strong Lewis acidic character. The excellent catalytic activity of 1 for the hydroboration of organic compounds with carbonyl groups was investigated. Furthermore, it was shown that 1 effectively initiates the addition reaction of trimethylsilyl cyanide (TMSCN) to both aldehydes and ketones. Quantum mechanical calculations were carried out to explore the reaction mechanism.

Stabilization of a two-coordinate mononuclear cobalt(0) compound.

Compound (Me2 -cAAC:)2 Co(0) (2; Me2 -cAAC:=cyclic (alkyl) amino carbene; :C(CH2 )(CMe2 )2 N-2,6-iPr2 C6 H3 ) was synthesized by the reduction of the precursor (Me2 -cAAC:)2 Co(I) Cl (1) with KC8 in THF. The cyclic voltammogram of 1 exhibited one-electron reduction, which suggests that synthesis of a bent 2-metallaallene (2) from 1 should be possible. Compound 2 contains one cobalt atom in the formal oxidation state zero, which is stabilized by two Me2 -cAAC: ligands. Bond lengths from X-ray diffraction are 1.871(2) and 1.877(2) Šwith a C-Co-C bond angle of 170.12(8)°. The EPR spectrum of 2 exhibited a broad resonance attributed to the unique quasi-linear structure, which favors near degeneracy and gives rise to very rapid relaxation conditions. The cAACCo bond in 2 can be considered as a typical Dewar-Chatt-Duncanson type of bonding, which in turn retains 2.5 electron pairs on the Co atom as nonbonding electrons.

Be2+ Causes Hypersensitivity but Mg2+ and Ca2+ Do Not─Favorable Metal Coordination Is the Key for Differential Allosteric Modulation and Binding Affinities.

Although the ion selectivity of metalloproteins has been well established, selective metal antigen recognition by immunoproteins remains elusive. One such case is the recognition of the Be2+ ion against its heavier congeners, Mg2+ and Ca2+, by the human leukocyte antigen immunoprotein (HLA-DP2), leading to immunotoxicity. Integrating with our previous mechanistic study on Be2+ toxicity, herein, we have explored the basis of characteristic nontoxicity of Mg2+ and Ca2+ ions despite their in vivo abundance. The ion binding cleft of the HLA-DP2-peptide complex is composed of four acidic residues, p4D and p7E from the peptide and ß26E and ß69E from the protein. While the tetrahedral coordination site of the smaller Be2+ ion is located deep inside the cavity, hexa- to octa-coordination sites of Mg2+ and Ca2+ ions are located closer to the protein surface. The intrinsic high coordination number of Mg2+/Ca2+ ions induces allosteric modifications on the HLA-DP2_M2 surface, which are atypical for TCR recognition. Furthermore, the lower binding energy of larger Mg2+ and Ca2+ ions with the cavity residues can be correlated to the lower charge density and reduced covalent bonding nature as compared to those of the smaller Be2+ ion. In short, weak binding of Mg2+ and Ca2+ ions and the unfavorable allosteric surface modifications are probably the major determinants for the absence of Mg2+/Ca2+ ion-mediated hypersensitivity in humans.

Site-selective post-modification of short α/γ hybrid foldamers: a powerful approach for molecular diversification towards biomedical applications.

The extensive research work in the exhilarating area of foldamers (artificial oligomers possessing well-defined conformation in solution) has shown them to be promising candidates in biomedical research and materials science. The post-modification approach is successful in peptides, proteins, and polymers to modulate their functions. To the best of our knowledge, site-selective post-modification of a foldamer affording molecules with different pendant functional groups within a molecular scaffold has not yet been reported. We demonstrate for the first time that late-stage site-selective functionalization of short hybrid oligomers is an efficient approach to afford molecules with diverse functional groups. In this article, we report the design and synthesis of hybrid peptides with repeating units of leucine (Leu) and 5-amino salicylic acid (ASA), regioselective post-modification, conformational analyses (based on solution-state NMR, circular dichroism and computational studies) and morphological studies of the peptide nanostructures. As a proof-of-concept, we demonstrate the applications of differently modified peptides as drug delivery agents, imaging probes, and anticancer agents. The novel feature of the work is that the difference in reactivity of two phenolic OH groups in short biomimetic peptides was utilized to achieve site-selective post-modification. It is challenging to apply the same approach to short α-peptides having a poor folding tendency, and their post-functionalization may considerably affect their conformation.

Electronic structure of six-membered N-heterocyclic carbenes and its heavier analogues: reactivity of the lone pair versus the exocyclic double bond.

Electronic structure of the six-membered N-heterocyclic carbene, silylene, germylene, and stannylene having an exocyclic double bond at the C3 carbon atom as well as the relative reactivity of the lone-pair on the divalent group 14 element and the exocyclic double bond have been studied at the BP86 level of theory with a TZVPP basis set. The geometrical parameters, NICS values, and NBO population analysis indicate that these molecules can be best described as the localized structure 1X(a), where a trans-butadiene (C1-C2-C3-C4) unit is connected with diaminocarbene (N1-X-N2) via N-atoms having a little contribution from the delocalized structure 1X(b). The proton affinity at X is higher than at C4 for 1C, and a reverse trend is observed for the heavier analogues. Hence, the lone pair on a heavier divalent Group 14 element is less reactive than the exocyclic double bond. This is consistent with the argument that, even though the parent six-membered carbene and its heavier analogues are nonaromatic in nature, the controlled and targeted protonation can lead to either the aromatic system 3X having a lone pair on X or the nonaromatic system 2X with readily polarizable C3-C4 π-bond. The energetics for the reaction with BH(3) and W(CO)(6) further suggest that both the lone pair of Group 14 element and the exocyclic double bond can act as Lewis basic positions, although the reaction at one of the Lewis basic positions in 1X does not considerably influence the reactivity at the other. The protonation and adduct formation with BH(3) and W(CO)(5) at X lead to nonaromatic systems whereas similar reactions at C4 lead to aromatic systems due to π-bond polarization at C3-C4. The degree of polarization of the C3-C4 π-bond is maximum in the protonated adduct and reduces in the complexes formed with BH(3) and W(CO)(5).

Cation-π and hydrophobic interaction controlled PET recognition in double mutated cutinase - identification of a novel binding subsite for better catalytic activity.

Accelerated hydrolysis of polyethylene terephthalate (PET) by enzymatic surface modification of various hydrolases, which would not degrade the building blocks of PET in order to retain the quality of recycled PET, is a promising research area. Many studies have been reported to identify mutations of different hydrolases that can improve PET degradation. Recently, the mutation of glycine and phenyl alanine with alanine in cutinase was found to improve the activity of PET degradation 6-fold. Yet, a deep insight into the overall structural basis as well as the explicit role played by the amino acid residues for PET degradation is still elusive, which is nevertheless important for comparative analyses, structure-function relations and rational optimization of the degradation process. Our molecular dynamics simulations coupled with quantum mechanical study demonstrate that mutations of anchor residue phenyl alanine to alanine at the PET binding cleft of cutinase unveiled a distal yet novel binding subsite, which alters the nature of dispersive interaction for PET recognition and binding. The phenyl alanine engages in π-π interaction with the phenyl ring of PET (-8.5 kcal mol-1), which on one side helps in PET recognition, but on the other side restricts PET to attain fully extended conformations over the entire binding cleft. The loss of π-π interaction due to mutation of phenyl alanine to alanine is not only compensated by the favourable cation-π and hydrophobic interactions from the arginine residues (-17.1 kcal mol-1) found in the newly discovered subsite, but also favours the fully extended PET conformation. This subsequently impacts the overall increased catalytic activity of mutated cutinase.

Effect of ancillary ligand on DNA and protein interaction of the two Zn (II) and Co (III) complexes: experimental and theoretical study.

In the present work we have developed one mononuclear Zn(II) complex [Zn(L)(H2O)] (Complex 1) by utilizing a tetracoordinated ligand H2L, formed by simple condensation of 2, 2 dimethyl 1,3 diamino propane and 3- ethoxy salicylaldehyde and one newly designed mononuclear Co (III) complex [Co(L)(L1)] (complex 2) by utilizing (H2L) and 3- ethoxy salicylaldehyde(HL1) as an ancillary ligand. The newly developed complex 2 have been spectroscopically characterized. An interesting phenomenon has been noticed that in presence of ancillary ligand, the solubility in buffer solution and the thermal stability of complex 2 comparatively increases than 1. To check the effect of ancillary ligand, present in complex 2 towards the DNA and HSA binding efficacy, both the complexes have been taken into consideration to inspect their binding potentiality with the macromolecules. The 'on', 'off' fluorescence changes in presence of DNA and HSA, the binding constant values, obtained from electronic spectral titration, iodide induced quenching, competitive binding assay, circular dichroism (CD) spectral titration, time resolved fluorescence experiment unambiguously assure the better binding efficacy of complex 2 with the signal of minor groove binding mode with DNA along with no significant conformational changes of the macromolecules. The strong and spontaneous binding of complex 2 with CT-DNA is further supported by the Isothermal Titration Calorimetry (ITC) study. Furthermore TDDFT calculation of DNA with and without complex 2 significantly authorize the formation of complex 2-DNA adduct during the association. Finally Molecular Docking study properly verifies the experimental findings and provides justified explanation behinds experimental findings.

Borylene-based functionalization of iron-alkynyl-σ-complexes and stepwise reversible metal-boryl-to-borirene transformation: synthesis, characterization, and density functional theory studies.

Thermally induced chemoselective borylene transfer from [(OC)(5)Mo=BN(SiMe(3))(2)] (2a) to the carbon-carbon triple bond of an iron dicarbonyl alkynyl complex [(η(5)-C(5)Me(5))Fe(CO)(2)C≡CPh] (3) led to the isolation of an iron aminoborirene complex [(η(5)-C(5)Me(5))(OC)(2)Fe{µ-BN(SiMe(3))(2)C=C}Ph] (4) in satisfactory yield. Room temperature photolysis of 4 resulted in an unprecedented rearrangement and a concurrent decarbonylation, affording the novel C(2) side-on coordinated iron boryl complex [(η(5)-C(5)Me(5))(OC)FeBN(SiMe(3))(2)(η(2)-CC)Ph] (5). Carbonylation of 5 under CO atmosphere at ambient temperature yielded [(η(5)-C(5)Me(5))(OC)(2)FeBN(SiMe(3))(2)CCPh] (6), which is an isomer of 4. Decarbonylation of 6 at 80 °C led to 5, which could be upon introduction of CO gas further converted into 4 under same conditions. Reaction of 5 with PMe(3) at 80 °C yielded the phosphane complex [(η(5)-C(5)Me(5))(OC)(PMe(3))Fe{µ-BN(SiMe(3))(2)C=C}Ph] (7). All above-mentioned iron complexes 4-7 were isolated as air and moisture sensitive crystalline solids in good yields and have been fully characterized in solution and by X-ray crystallography. Quantum chemical calculations using density functional theory (DFT) have been carried out to understand the mechanisms of the experimentally observed reactions and to analyze the bonding situation in the molecules 4-7.

Dual-Site Binding of Quaternary Ammonium Ions as Internal K+-Ion Channel Blockers: Nonclassical (C-H···O) H Bonding vs Dispersive (C-H···H-C) Interaction.

A molecular-level study of the influence of the alkyl chain length of quaternary ammonium ions (QAs) on the blocking action and the mode of binding with the bacterial KcsA K+-ion channel is carried out by molecular dynamics (MD) simulations as well as quantum mechanics/molecular mechanics (QM/MM) methods. The present work unveils distinct modes of binding for different QAs, due to differences in size and hydrophobicity. The QAs bind near the channel gate as well as at the central cavity, leading to a possible dual-site blocking action. Small-sized tetraethylammonium (TEA) and tetrabutylammonium (TBA) ions enter inside the channel cavity in the open state of KcsA but bind strongly in the closed state. TEA binds to the polar hydroxyl group of threonine residues situated at the channel gate via nonclassical H-bonding interaction (C-H···O), while TBA binds to a second binding site, the central cavity, with hydrophobic benzyl and sec-butyl side chains of phenylalanine and isoleucine residues via alkyl-π and hydrophobic interactions (C-H···H-C). On the contrary, large tetrahexylammonium (THA) and tetraoctylammonium (TOA) ions bind the hydrophobic side-chain methyl and isopropyl of alanine and valine at the channel gate both in the open and closed states, thereby restricting the free movement of large QAs toward the center of the cavity. However, the binding to the hydrophobic benzyl and sec-butyl side chains of phenylalanine and isoleucine residues in the closed state is thermodynamically preferable. Also, the binding energy is found to increase with an increase in the alkyl chain length from ethyl (-16.4 kcal/mol) to octyl (-65.5 kcal/mol), due to an almost linear increase in dispersive interaction.

Design, synthesis, and DNA binding properties of photoisomerizable azobenzene-distamycin conjugates: an experimental and computational study.

Here, we present the synthesis, photochemical, and DNA binding properties of three photoisomerizable azobenzene-distamycin conjugates in which two distamycin units were linked via electron-rich alkoxy or electron-withdrawing carboxamido moieties with the azobenzene core. Like parent distamycin A, these molecules also demonstrated AT-specific DNA binding. Duplex DNA binding abilities of these conjugates were found to depend upon the nature and length of the spacer, the location of protonatable residues, and the isomeric state of the conjugate. The changes in the duplex DNA binding efficiency of the individual conjugates in the dark and with their respective photoirradiated forms were examined by circular dichroism, thermal denaturation of DNA, and Hoechst displacement assay with poly[d(A-T).d(T-A)] DNA in 150 mM NaCl buffer. Computational structural analyses of the uncomplexed ligands using ab initio HF and MP2 theory and molecular docking studies involving the conjugates with duplex d[(GC(AT)10CG)]2 DNA were performed to rationalize the nature of binding of these conjugates.