Interconversion Equilibrium Research Articles

The crystal structures of Imine-Enamine ‘tautomerism’ in solid state and “turn on” sensing for Zn2+: spectroscopy, DFT and cell imaging studies

The crystallographically established ligand 2-((E)-(benzyl imino)methyl)-4-bromophenol (HL) (existing keto at 296 K and enol at 120 K in the solid state), which is in equilibrium of interconversion (ΔE) = 4.39Kcal) with its tautomer, showed weak emission in the excited state, due to the fact of PET but in the presence of Zn2+, PET was blocked and chelation-enhanced fluorescence (CHEF) was set up. It exhibits 'turn on' sensor with the coordination of Zn2+. Among various metal ions, the synthesised probe HL selectively detected Zn2+ and LOD was about to ∼ 1.63 µM. The Zn(II) coordinated complex and the relative stabilities of the tautomers of HL were thoroughly calculated by spectroscopic and computational studies. Furthermore, cell imaging was also performed to validate the sensing property as well as cyto-toxicity of the probe.

Development of Heterobimetallic Al/Mg Complexes for the Very Rapid Ring-Opening Polymerization of Lactides.

The successful architecture of active catalytic species with enhanced efficiencies is critical for the optimal exploitation of sustainable resources in industrially demanded processes. In this work, we describe the preparation of novel helical heterobimetallic Al/Mg-based complexes of the type [AlMe2(pbpamd-)MgR{κ1-O-(OC4H8O)}] [R = Et (1a), tBu (2a)] as potential catalysts. The design was performed through the sequential addition of the Al fragment to the ligand, followed by the Mg platform, resulting in a planar π-C2N2(sp2)-Al/Mg bridging core between metals. The new heterobimetallic species have been unambiguously characterized by single-crystal X-ray analysis. NOESY, DOSY, and EXSY NMR studies as well as density functional theory calculations corroborate both a rearrangement in solution to scorpionate complexes containing an unprecedented apical carbanion with a direct σ-C(sp3)-Al covalent bond named [{Mg(R)(pbpamd-) Al(Me)2}] [R = Et (1b), tBu (2b)] and an interconversion equilibrium between both isomers. We verified their utility and high efficiency as catalysts in the well-controlled ring-opening polymerization of the biorenewable l- and rac-lactide (LA) at 23 °C, reaching a remarkable turnover frequency value close to 25000 h-1 for rac-LA at this temperature and exerting a significant level of heteroselectivity (Pr = 0.80). Very interestingly, the kinetics demonstrate apparent first-order with respect to the catalyst and LA, which supports a synergic intramolecular cooperation between centers with electronic modulation among them.

A critical evaluation of barium silicate glass network polymerization

The state of polymerization in barium silicate glasses (xBaO·(1-x)SiO2, 0.28 ≤ x ≤ 0.45) has been studied by both experiment (Raman, static and MAS 29Si NMR spectroscopy) and molecular dynamics simulations (Vashishta-Rahman and Du-Cormack potentials). No a priori assumptions were made about the number of Qn species, specific mean polymerization nor presence or absence of ‘free’ oxygen species. This allowed us to test the relationships between these structural aspects.The Qn site interconversion equilibrium constants KQ2 and KQ3 were found to be 0.07 and 0.05±0.02 from static 29Si NMR, and 0.14±0.07 and 0.07±0.01 from 29Si MAS NMR, respectively. The Qn species distribution was used to determine the Raman scattering cross-sections for Q1, Q2 and Q3 as 1.01±0.15, ∼1.1, and 1.14±0.04, respectively, although some compositional dependence was found. The Q4 cross-section displays a unique behavior approaching 0 at 38% BaO. This more accurate structural framework paves the way for future studies to establish meaningful structure−property relationships for these glasses.

New preparation protocols for coumarin-thiosemicarbazone hybrids: Solid state characterization, and in silico/NMR studies of the Z/E isomerization equilibria in solution

In this work, two improved experimental protocols for the preparation of eight coumarin-thiosemicarbazone hybrids are described. The novel methodologies, based on the use of a microwave-assisted protocol (MW) or a sealed vessel conventionally heated reactor (SVR) are faster, more efficient and render higher yields (average increase in yield = 11% and 16%, respectively). For the solid state characterization, infrared spectra of the obtained compounds were analyzed with the aid of computational tools for signal assignation. In addition, a new crystal structure for the E isomer of compound 2d was obtained and a thorough analysis of the intra and intermolecular interactions was performed by Hirshfeld surface analysis. On the other hand, the hybrids were characterized in DMSO-d6 solution by 1H and 13C NMR experiments. All of them showed a set of minor signals neither ascribable to the products nor described in the literature. Variable temperature 1H NMR experiments revealed that a single interconversion equilibrium was operative in the solution, having thermodynamic parameters compatible to those predicted for a Z/E isomerization process by a DFT model. The most stable configuration (E) was further confirmed by DFT, calculating the 13C NMR chemical shifts for both configurations. The computational model shows that the E configuration is stabilized through the formation of a non-conventional C-H···O=C intramolecular H-bond between the methyl and carbonyl groups, adopting a conformation less sterically strained. These findings allow to gain insights into the E/Z isomerization equilibria displayed by thiosemicarbazones in solution, a phenomenon usually under described in literature, which seems to be promoted by a balance between weak intramolecular interactions that modulate the relative isomeric stability in solution.

Existence of α‐mangostin conformers and effects of aprotic and protic solvents on their equilibria, UV–Vis spectra, and chemical descriptors: Density functional theory and time‐dependent density functional theory study

AbstractThe physicochemical, thermodynamic, spectroscopic, and electronic properties of α‐mangostin dye (1,3,6‐trihydroxy‐7‐methoxy‐2,8‐bis(3‐methyl‐2‐buten‐1‐yl)‐9H‐xanthen‐9‐one) were investigated. Five conformers of the α‐mangostin dye were obtained using three different polarizable continuum model (PCM)/density functional theory (DFT) methods: wB97XD/6‐31+G(d,p), M06‐2X/6‐31+G(d,p), and B3LYP/6‐31+G(d,p). The species distribution of the five conformers in acetonitrile, water, and the gas phase was derived from the Gibbs free energy changes of their interconversion equilibria. Three dominant conformers (Conformers 2, 3, and 4) were found as coexisting species in solvents. Chemical descriptors of the three dominant conformers of the α‐mangostin in acetonitrile and water were obtained. Simulated UV–Vis spectra of the existing conformers and their mixtures in acetonitrile and water derived from the PCM/TD‐DFT calculations were in good agreement with experimental results. Because the three dominant conformers of α‐mangostin absorb light in the UV region, the application of α‐mangostin dye for UV protection is suggested. The performance of the three dominant α‐mangostin conformers in dye sensitized solar cells was also investigated.

Di-oxo and tri-oxo Re(VII)-oxosulfato complexes in the Re2O7-K2S2O7 molten system. Molecular structure, vibrational properties and temperature-dependent interconversion

The reaction between Re2O7 and K2S2O7 in the molten phase is studied by Raman spectroscopy under static equilibrium oxidative conditions at temperatures of 260–470 °C and in the full composition range, XRe2O70=0−1. Raman band intensity correlations are adequate for inferring a 1:1 stoichiometry for the complex formation reaction. Depending on temperature and on composition of the mixture, two isomeric ReVII-oxosulfato complexes are formed: (a) ReO3SO4−, prevalent at low temperature (T<300 °C), where penta-coordinated ReVII takes on a tri-oxo termination configuration; and (b) (ReO2)2O2(SO4)22-, dominant at high temperature (T>360 °C), with hexa-coordinated ReVII in di-oxo termination configuration. The characteristic symmetric and antisymmetric stretching modes (νs/νas) of the Re(=O)3+ and Re(=O)23+ cores are found at 975/938 cm-1 and 989/944 cm-1 for the tri-oxo and di-oxo sites, respectively. A fully reversible temperature-dependent 2ReO3SO4−(l) ↔ (ReO2)2O2(SO4)22-(l) interconversion equilibrium is evidenced. Consistent molecular structural models are proposed for the ReO3SO4− and (ReO2)2O2(SO4)22- complexes as well as for their associated/polymeric counterparts, (ReO3SO4)nn- and ((ReO2)2O2(SO4)2)n2n-. Molten Re2O7 reacts with K2SO4 according to Re2O7(l) + 2SO42- → ReO4−(l) + S2O72-(l). The ReVII-oxosulfato complexes and their configurational, structural and vibrational properties are of interest as references for inferring corresponding properties for dispersed amorphous oxo-ReVII species in supported rhenia catalysts.

A ratiometric solvent polarity sensing Schiff base molecule for estimating the interfacial polarity of versatile amphiphilic self-assemblies.

A newly synthesised Schiff base molecule (PMP) existing in equilibrium between non-ionic and zwitterionic forms displays solvent polarity induced ratiometric interconversion from one form to another, such novelty being useful to detect the medium polarity. The specific interface localisation of PMP in versatile amphiphilic self-assembled systems has been exploited to monitor their interfacial polarity by evaluating such interconversion equilibrium with simple UV-Vis spectroscopy. In spite of the large differences in pH and/or viscosity between the bulk and interface, the unchanged equilibrium between the two molecular forms on varying the medium pH or viscosity provides a huge advantage for the exclusive detection of interfacial polarity.

Self-assembly of BODIPY based pH-sensitive near-infrared polymeric micelles for drug controlled delivery and fluorescence imaging applications

Responsive block copolymer micelles emerging as promising imaging and drug delivery systems show high stability and on-demand drug release activities. Herein, we developed self-assembled pH-responsive NIR emission micelles entrapped with doxorubicin (DOX) within the cores by the electrostatic interactions for fluorescence imaging and chemotherapy applications. The block copolymer, poly(methacrylic acid)-block-poly[(poly(ethylene glycol) methyl ether methacrylate)-co-boron dipyrromethene derivatives] (PMAA-b-P(PEGMA-co-BODIPY), was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, and the molecular weight distribution of this copolymer was narrow (Mw/Mn = 1.31). The NIR fluorescence enhancement induced by the phenol/phenolate interconversion equilibrium works as a switch in response to the intracellular pH fluctuations. DOX-loaded PMAA-b-P(PEGMA-co-BODIPY) micelles can detect the physiological pH fluctuations with a pKa near physiological conditions (∼7.52), and showed pH-responsive collapse and an obvious acid promoted anticancer drug release behavior (over 58.8-62.8% in 10 h). Real-time imaging of intracellular pH variations was performed and a significant chemotherapy effect was demonstrated against HeLa cells.

Conformation and Self-Assembly of the Transmembrane Peptide Gramicidin A: Insights from ion Mobility Spectrometry and Molecular Dynamics

Gramicidin A which is composed of alternating L- and D-amino acids is a naturally occurring pentadecapeptide from Bacillus brevis known to form monovalent metal ion channels in lipid membranes. The active form is a noncovalently bound dimer. The conformation and self-assembly behavior of gramicidin A highly depends on the solution environment. In this presentation, we report the use of electrospray-ion mobility-mass spectrometry to study the conformation of alkali metals adducts of gramicidin A monomer, as well as the monomerization and conformer interconversion equilibrium of gramicidin A dimer as a function of the solvent. The conformation of gramicidin A monomer vary significantly upon binding different metal adducts. Enhanced sampling molecular dynamics simulations are performed on alkali metals adducts to provide thermodynamics information of different conformers and gain insights of the interaction of different metal ions with the monomer. The kinetics of the monomerization and conformer interconversion processes of dimer in various alcohol solutions (Ethanol, 1-Propanol and, Isobutanol) are monitored by using the ion mobility profile of the monomer and the dimer. The rate constants and the temperature dependence of the rate constants of the monomer compare well with literature values which were obtained by using fluorescence. Furthermore, we found that the water content in the alcohol solution greatly influences the self-assembly process significantly. The role of water in catalyzing the conformer interconversion is being investigated further. Ion mobility spectrometry (IMS) combined with molecular dynamics simulations is a merging technique for conformational analysis of gas-phase low-lying energy level structures of biomolecules. In this study, we will demonstrate that this gas phase technique can also be of utility in studying a solution phase structural dynamics problem.

Human Pharmacokinetics and Interconversion of Enantiomers of MK‐0767, a Dual PPARα/γ Agonist

MK-0767, a dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist, has been studied as a potential treatment of type 2 diabetes and dyslipidemia. The pharmacokinetics and interconversion of (+)-(R)-MK-0767 and (-)-(S)-MK-0767 were evaluated following oral administration of each single enantiomer and the racemate to healthy subjects. The results demonstrate that, consistent with in vitro experiments, chiral inversion occurs rapidly in vivo, and interconversion equilibrium favors (+)-(R). After all treatments, a stable ratio (R/S) of 2 to 2.5 was achieved within 8 hours in most individuals, congruent with model-based estimates of interconversion half-life. In addition, the pharmacokinetics of each enantiomer were generally similar regardless of treatment. Modeling and simulation of enantiomer disposition suggest that the observed predominance of (+)-(R)-MK-0767 in plasma may result from differential volumes of distribution between (-)-(S) and (+)-(R), preferential conversion from (-)-(S) to (+)-(R), or a combination of these, but not faster clearance of (-)-(S) compared to (+)-(R).

A DFT investigation of conformational geometries and interconversion equilibria of phenylthiosemicarbazone and its complexation with zinc

The geometrical structures of phenylthiosemicarbazone (HAPhTSC) conformers have been obtained by geometry optimizations using density functional theory (DFT) calculations at the B3LYP/6-31G(d) and B3LYP/6-311G(d,p) levels of theory. Six thioamino and 24 thioimino tautomers of HAPhTSC have been found. Six tautomerization reactions between thioamino and thioimino tautomers occurring via transition states and their corresponding activation energies have been obtained. Conformational pathways for tautomerizations and interconversions of HAPhTSC conformers have been presented. Tautomerization between the most stable species of thioamino (Atttcc) and its thioimino (Itttcct) tautomer is an endothermic reaction, Delta H(0)=18.17 kcal mol(-1) and its log K=-13.74, at 298.15 K. Thermodynamic quantities of tautomerizations, interconversions of HAPhTSC conformers and their equilibrium constants are reported. The geometry of the zinc complex with HAPhTSC, found as a Zn(HAPhTSC)2Cl2 structure, has been obtained using B3LYP/6-31G(d) calculations. Binding of the Zn(HAPhTSC)2Cl2 complex is an exothermic and spontaneous reaction. [figure]. Conformational notation defined as a name consisting of a letter "A" for A thioamino tautomer followed by "c" for cis or "t" for trans isomerism of five dihedral angles of chi(C4-C3-C2-N3), phi(C3-C2-N3-N2), psi(C2-N3-N2-C1), theta;(N3-N2-C1-N1) and omega(N2-C1-N1-H2), serially, or a letter "I" for B thioimino tautomer followed by "c" for cis or "t" for trans isomerism of six dihedral angles of chi(C4-C3-C2-N3), phi(C3-C2-N3-N2), psi(C2-N3-N2-C1), theta(N3-N2-C1-N1), omega(N2-C1-N1-H2) and delta (N2-C1-S-H1), serially.

Oxidation of Thioanisole by Peroxomolybdate in Assemblies of Cetylpyridinium Chloride and Methyltri-n-octylammonium Chloride

Methyltri-n-octylammonium chloride (Aliquat 336) is sparingly soluble in water but is readily soluble with a 2-fold excess of micellized cetylpyridinium chloride (CPyCl), and the mixtures show breaks in plots of surface tension or electrolytic conductance against concentration indicative of a critical micelle concentration slightly lower than that of CPyCl. Micellization markedly increases 35Cl and 14N NMR line widths of CPyCl, but addition of NaCl reduces the 35Cl line width and addition of Aliquat increases it. Mixing Aliquat and CPyCl has little effect on their 14N line widths. Ion pairing in alcohol mixtures also increases 35Cl line widths. In water these mixed assemblies behave similarly to micelles of CPyCl as regards effects on rates and equilibria of interconversion of tri- and tetraperoxomolybdate ions, and oxidation of thioanisole by the latter, although it is slightly slower than in micelles of CPyCl. Despite differences in the hydrophobic regions, and relationships between amphiphilic structures and morphologies of association colloids, assemblies of CPyCl and Aliquat behave very much like CPyCl micelles in their physical properties and effects upon reactivity. Geometrical optimization indicates that Aliquat can adopt conformations that allow intercalation with CPyCl micelles.

Further insights on the high–low spin interconversion in nickel(ii) tetramine complexes. Solvent and temperature effects

The spin interconversion equilibrium involving the [Ni(II)(cyclam)]2+ complex has been investigated in a variety of polar solvents, at varying temperatures. The greater the donor tendencies of the solvent, the higher the endothermicity of the high-to-low-spin conversion. In particular, a positive linear relationship exists between DeltaHdegrees and Gutmann's Donor Number (DN). In the same way, higher donor tendencies of the solvent favour the occurrence of the Ni(II)-to-Ni(III) oxidation process and negative linear relationship has been found between the E1/2(Ni(III)/Ni(II)) and DN. General behaviour is related to the intensity of the metal-solvent axial bonds in the octahedrally elongated cyclam complexes (of both Ni(II) and Ni(III)).

Properties and Mechanism of Molybdenum and Zirconium Adsorption by a Macroporous Silica‐Based Extraction Resin in the MAREC Process

To achieve effective separation of molybdenum and zirconium in the MAREC process, the adsorption properties and mechanism of Mo(VI) and Zr(IV) with a macroporous CMPO/SiO2‐P (CMPO: octyl(phenyl)‐N,N‐diisobutylcarbamoylmethylphosphine oxide) extraction resin have been studied. By investigating the influence of the aqueous concentrations of H+ and NO3 − on the adsorption of Mo(VI), the composition of complex of Mo(VI) and CMPO/SiO2–P is determined as H2MoO4 · 2CMPO/SiO2–P for dilute aqueous HNO3 and H2MoO3 (NO3)2 · 2CMPO/SiO2–P for concentrated aqueous HNO3, respectively. Similarly, the composition of Zr(IV) and CMPO/SiO2–P is determined as ZrO(NO3)2 · 2CMPO/SiO2–P or Zr(NO3)4 · 2CMPO/SiO2–P in 0.3–4.0 M HNO3, while ZrO2 · 2H2O · 2CMPO/SiO2–P is assumed for lower HNO3 concentration. Based on the compositions of Mo(VI) and Zr(IV) with CMPO/SiO2–P and the elution behavior of Mo(VI) and Zr(IV) by using 0.05 M diethylenetriaminepentaacetic acid (DTPA) at 0.01–1.0 M HNO3, a dynamic interconversion equilibrium between the complexes of Mo(VI) or Zr(IV) and CMPO/SiO2–P is demonstrated to take place in the elution process. To verify the adsorption mechanism, the adsorption and elution behavior of Mo(VI) and Zr(IV) with 0.05 M DTPA‐pH 2.0 was performed from a simulated high level radioactive liquid waste (HLLW) containing Pd(II), Gd(III), Y(III), Eu(III), Sm(III), Mo(VI), and Zr(IV). The results indicate that Mo(VI) and Zr(IV) not only can be efficiently eluted with 0.05 M DTPA‐pH 2.0, but also the elution efficiency is much better than that of 0.5 M H2C2O4 previously used in the MAREC process. The reverse equilibrium of complexes between Mo(VI) or Zr(IV) and CMPO/SiO2–P in high and low acidity was demonstrated, respectively.

Water hexamer clusters: Structures, energies, and predicted mid-infrared spectra

We present an ab initio theoretical study of five low-energy isomers of the water hexamer {Chair, Cage(du)[1], Book, Prism, and Boat}, their intramolecular vibrations, binding energies De and dissociation energies D0. Møller–Plesset second order perturbation calculations using the aug-cc-pVTZ basis set at aug-cc-pVDZ optimized geometries including vibrational zero point energy corrections predict Chair to be the most stable isomer, followed closely by Cage(du)[1] (+0.02 kcal/mol) and Book (+0.05 kcal/mol), while Prism is 0.15 kcal/mol higher. The Boat conformer is least stable at both the De and D0 levels. The main focus is on the intramolecular normal modes of the five isomers. The calculated O–H stretching frequencies and intensities are compared to recent infrared spectra of water hexamer in supersonic jets, liquid-helium droplets and solid para-hydrogen matrices. The IR spectra indicate that Book and Chair are major species in the latter two environments and may also exist in supersonic jets. The (H2O)6 gas phase interconversion equilibria are calculated and predict that the most abundant isomer is Chair below 8 K, Cage between 8–26 K, and Book above 26 K. Several of the low-frequency vibrational modes are identified as low-amplitude precursors of the Chair↔Book↔Cage isomerization pathways.

A bis-bidentate dioxolene ligand induces thermal hysteresis in valence tautomerism interconversion processes.

The use of a bis-bidentate ligand in a solid cobalt dioxolene complex affords the necessary cooperative properties that lead to thermal hysteresis in a valence tautomeric interconversion equilibrium.

Carboxy-terminal extension stabilizes the topological stereoisomers of guanylin.

The peptide hormone guanylin constitutes two topological stereoisomers, which are connected through an equilibrium of interconversion. To investigate the importance of amino acid residues in the central region between the inner cysteines and at the carboxy terminus for this isomerism, synthetic derivatives of guanylin were compared by HPLC, 2D1H NMR spectroscopy and by their guanylyl cyclase-C (GC-C)-activating potency. An increase in the central sterical bulk by introduction of diiodo-Tyr9 had virtually no effect on the isomerization kinetics. Compared to guanylin, carboxy-terminal amidation did not affect the equilibrium between the two isoforms either. In contrast, two significantly stabilized isomers were obtained by extending the carboxy terminus of guanylin with one additional leucine resembling the characteristic of human uroguanylin isomers. This effect was intensified by a further Lys-Lys extension, thus revealing that the conformational exchange between the guanylin isomers is dependent on the extent of the sterical hindrance in the carboxy-terminal region of this peptide. Demonstrated by 2D NMR spectroscopy, the separated isomers of the carboxy-terminally extended derivatives of guanylin exhibit unambiguously closely related structures as found originally for guanylin isomers, which are only detectable as a mixture. Because only one of the stabilized guanylin isomers activates guanylyl cyclase-C, the three-dimensional structure of the GC-C-activating guanylin isomer is now defined. The stabilized isoforms of guanylin described in this study represent suitable tools for the separate functional investigation of the GC-C-agonistic isomer of guanylin as well as of its isomeric counterpart.

Studies on the neuroexcitotoxin beta-N-oxalo-L-alpha,beta-diaminopropionic acid and its isomer alpha-N-oxalo-L-alpha,beta-diaminopropionic acid from the root of Panax species.

The neuroexcitotoxic nonprotein amino acid, beta-N-oxalo-L-alpha,beta-diaminopropionic acid (beta-N-ODAP) was found in Panax species such as Panax ginseng 'C.A. Meyer' (cultivated in Northeastern China), Panax quinquefolius (L), Panax notoginseng 'F.H. Chen' (cultivated in Southwestern China), Korean red ginseng and Jilin (China) red ginseng. beta-N-ODAP was verified to be a natural substance, and its isomer alpha-N-oxalo-L-alpha,beta-diaminopropionic acid (alpha-N-ODAP) is very likely an artifact generated during the separation process. The interconversion between beta-N-ODAP and alpha-N-ODAP was observed. Results showed that both beta-N-ODAP and alpha-N-ODAP can easily be converted into their isomers at higher temperature or in acidic and basic solution. Their interconversion equilibrium constant and rate constants were obtained. Upon extensive study and a good understanding of the interconversion, accurate physical constants and spectroscopic data such as MS, 1H NMR, 13C NMR and UV were obtained.

Isomerization mechanism of dinuclear chloro-bridged rhodium(I) complexes

At room temperature the cis- and trans-halide-bridged dimers [{Rh(CO) (PPh 3)(μ-Cl)} 2] give rise to a rather fast equilibrium of interconversion. NMR spectra provide evidence that during the reaction neither rhodium-phosphorus nor rhodium-carbon bonds are broken. These results suggest that the equilibrium takes place through dissociation of the dinuclear Rh 1 species into the tricoordinated 14-electron T-shaped fragments [Rh(CO)(PPh 3)Cl]. In keeping with this suggestion, the rate of the isomerization is accelerated by the presence in solution of small amounts of cis-[Rh(CO) 2(PPh 3)(μ-Cl)], a complex which can be considered a precursor of the tricoordinated fragment [Rh(CO)(PPh 3)Cl].

Case study of protein structure, stability, and function: NMR investigations of the proline residues in staphylococcal nuclease

Abstract