Trans Equilibrium Research Articles

Two conformational states of Turkey ovomucoid third domain at low pH: three-dimensional structures, internal dynamics, and interconversion kinetics and thermodynamics.

Turkey ovomucoid third domain (OMTKY3) is shown to exist at low pH as two distinctly folded, interconverting conformations. Activation parameters were determined for the transition, and these were of the type reported previously for cis/trans isomerizations of prolyl peptide bonds. Multidimensional, multinuclear NMR spectroscopy was used to determine the three-dimensional structure of each of the two states of P(5)-Pro(14)Asp OMTKY3 at pH 2.5 and 25 degrees C, under conditions where the two states have equal populations with interchange rates of 0.25 s(-1). The results showed that the two states differ by cis/trans isomerization of the P(8)-Tyr(11)-P(7)-Pro(12) peptide bond, which is cis in the conformer dominant at neutral pH and trans in the conformer appearing at low pH. The major structural differences were found to be in the region of the reactive site loop. The core of the protein, including the antiparallel beta-sheet and a alpha-helix, is preserved in both structures. The state with the cis peptide bond is similar to previously reported structures of OMTKY3 determined by NMR spectroscopy and X-ray crystallography. The cis-to-trans transition results in the relocation of the aromatic ring of P(8)-Tyr(11), disrupts many interactions between the alpha-helix and the reactive-site loop, and leads to more open spacing between this loop and the alpha-helix. In addition, the configurations of two of the three disulfide bonds, P(11)-Cys(8)- P(20)'-Cys(38), and P(3)-Cys(16)- P(17)'-Cys(35), are altered such that the C(alpha)-C(alpha) distances for each disulfide bridge are longer by approximately 1 A in the trans state than in the cis. Mutations at P(1)-Leu(18), P(6)-Lys(13), and P(5)-Pro(14) influence the position of the cis <= => trans equilibrium. In P(1)-Leu(18)Xxx OMTKY3 mutants, the trans state is more favored by P(1)-Gly(18) than by Ala(18) or Leu(18); in P(6)-Lys(13)Xxx OMTKY3 mutants, the trans state is more favored by P(6)-Glu(13) and P(6)-Asp(13) than Lys(13) or His(13). Stabilization of the trans state in P(5)-Pro(14)Xxx OMTKY3 mutants follows the series Xxx = Gly > Asp > Glu > Ala approximately equal His > Pro. In comparing the state with the trans peptide bond to that with the cis, the pK(a) values of P(12)-Asp(7) and P(1)'-Glu(19) are higher and those of P(9)-Glu(10) and P(25)'-Glu(43) are lower. The pK(a) values of other titrating groups in the molecule are similar in both conformational states. These pK(a) changes underlie the pH dependence of the conformational equilibrium and can be explained in part by observed structural differences. (15)N transverse relaxation results indicate that residues P(6)-Lys(13)-P(3)-Cys(16) in the trans state undergo a dynamic process on the microsecond-millisecond time scale not present in the cis state.

Cis–trans Isomerization of N-acetyl-N′-methylamides of 5-methylproline and 5,5-dimethylproline

We report here the results on conformational free energies of N-acetyl-N′-methylprolineamide (Ac-Pro-NHMe) and its 5-methylated derivatives calculated using the ab initio and density functional methods with the self-consistent reaction field theory at the HF, MP2, and B3LYP levels of theory with the 6-31+G(d) basis set to investigate the influence of the 5-methylation on the structure, cis–trans equilibrium, and rotational barrier. The steric interactions imposed by the 5-methylation have resulted in the changes in the backbone structure and puckering of proline amides. The shorter distance between the acetyl methyl group and the 5-methyl group for the trans conformer than the cis conformer for each methylated proline amide appears to be crucial in destabilizing the trans conformer. The calculated cis populations and trans-to-cis rotational barriers in chloroform and water are consistent with observed results for Ac-5-MePro-NHMe and Ac-5-t-BuPro-NHMe. By analyzing the contributions to rotational barriers, the isomerization has proved to be entirely enthalpy-driven in the gas phase, chloroform, and water, to which the electronic energies have considerably contributed. The lower rotational barrier for the syn-5-MePro amide than the anti-5-MePro amide is ascribed to the large difference in the electronic energies of TS structures. The sp3 hybridization of the prolyl nitrogen for the TS structures confirmed by analyzing geometrical parameters as well as the pertinent distance between the prolyl nitrogen and the N–H amide group to form a hydrogen bond might indicate that this intramolecular hydrogen bond could contribute in stabilizing the TS structures of proline amide and its 5-methylated amides and play a role in prolyl isomerization.

Comparative conformational study of N-acetyl- N′-methylprolineamide with different basis sets

We report here the results on conformational free energies of N-acetyl- N′-methylprolineamide (Ac-Pro-NHMe) calculated using the ab initio and density functional methods with the reaction field theory at HF and B3LYP levels of theory with 6-31G(d,p) and 6-31+G(d) basis sets to investigate the effects of two different basis sets on the structure, cis– trans equilibrium, and rotational barrier of the proline dipeptide. There are no significant differences in the optimized structures for backbone and proline ring of Ac-Pro-NHMe at the HF level with 6-31G(d,p) and 6-31+G(d) basis sets. The relative electronic energies, enthalpies, and free energies with the 6-31+G(d) basis set are lower by 0.2–0.8 and 0.1–1.2 kcal/mol at HF and B3LYP levels than those with the 6-31G(d,p) basis set, respectively, which may be ascribed to the differences in the distribution of atomic charges. The HF/6-31+G(d) level has brought the unfavorable solvation by 0.1–1.5 kcal/mol in chloroform and water than the HF/6-31G(d,p) level, but there are small differences in dipole moments. The calculated cis populations and rotational barriers may indicate that the B3LYP/6-31+G(d)//HF/6-31+G(d) level combined by the frequency and solvation calculations at the HF/6-31+G(d) level appears to be the appropriate method in describing the cis– trans isomerization of the X-Pro peptide bond in solution.

Synthesis and characterization of a new chiral phosphinothiol ligand and its palladium(II) complexes

The chiral ligand (1-diphenylphosphino-3-benzyloxy)propane-2-thiol 3 has been prepared both in racemic and enantiomerically enriched (92% e.e.) form. Addition of 2 equiv. of ligand 3 to a solution of [Pd(PPh 3) 4] gave the diastereoisomeric bischelate complexes [Pd(phosphinothiolato) 2] 4 which exhibit a cis– trans equilibrium in solution. Formation of the diastereoisomeric complexes 4 allows the determination of the enantiomeric purity of ligand 3 by 31P NMR spectroscopy. Addition of 1 equiv. of ligand 3 to a solution of [PdCl 2(PPh 3) 2] gave the enantiomeric complexes [PdCl(phosphinothiolate)(PPh 3)] 5, which can be converted to the bischelate complexes 4 by addition of a second equivalent of ligand 3. This process allows the selective preparation of the two diastereoisomeric forms of complex 4.

Cis−Trans Isomerization and Puckering of Pseudoproline Dipeptides

We report here the results on N-acetyl-N‘-methylamides of oxazolidine and thiazolidine (Ac-Oxa-NHMe and Ac-Thz-NHMe) calculated using the ab initio and density functional computations with the reaction field theory at the HF, MP2, and B3LYP levels of theory with the 6-31+G(d) basis set. The displacement of the γ-CH2 group in proline ring by oxygen and sulfur atoms has affected the structure of proline, cis−trans equilibrium, and rotational barrier. The up-puckered structure is found to be prevalent for the trans conformers of pseudoproline amides. The higher cis populations of pseudoproline amides can be interpreted due to the longer distance between the acetyl methyl group and the 5-methylene group of the ring for the trans conformer of pseudoproline amides than that of the proline amide. The changes in charge of the prolyl nitrogen and the decrease in electron overlap of the C−N bond for transition state (TS) structures seem to play a role in lowering rotational barriers of Oxa and Thz amides compared to that of the proline (Pro) amide. The calculated preferences for cis conformers in the order of Oxa > Thz > Pro amides and for trans-to-cis rotational barriers in the order of Pro > Oxa > Thz amides in water are consistent with experimental results on pseudoproline-containing peptides. The pertinent distance between the prolyl nitrogen and the N−H amide group to form a hydrogen bond might indicate that this intramolecular hydrogen bond could contribute in stabilizing the TS structures of pseudoproline and proline amides and play a role in prolyl isomerization.

Experimental evidence for the noninnocence of o-aminothiophenolates: coordination chemistry of o-iminothionebenzosemiquinonate(1-) pi-radicals with Ni(II), Pd(II), Pt(II).

The ligand 2-mercapto-3,5-di-tert-butylaniline, H[L(AP)], an o-aminothiophenol, reacts with metal(II) salts of Ni and Pd in CH3CN or C2H5OH in the presence of NEt3 under strictly anaerobic conditions with formation of beige to yellow cis-[M(II)(L(AP))2] (M = Ni (1), Pd (2)) where (L(AP))1- represents the o-aminothiophenolate(1-) form. The crystal structure of cis-[Pd(II)(L(AP))2][HN(C2H5)3][CH3CO2] has been determined by X-ray crystallography. In the presence of air the same reaction produces dark blue solutions from which mixtures of the neutral complexes trans/cis-[M(II)(L(ISQ))2] (M = Ni (1a/1b), Pd (2a/2b), and Pt (3a/3b)) have been isolated as dark blue-black solid materials. By using HPLC the mixture of 3a/3b has been separated into pure samples of 3a and 3b, respectively; (L(ISQ))1- represents the o-iminothionebenzosemiquinonate(1-) pi-radical. The structures of 1a.dmf and 3a.CH2Cl2 have also been determined. All compounds are square-planar and diamagnetic. 1H NMR spectroscopy established the cis <==> trans equilibrium of 1a/1b, 2a/2b, and 3a/3b in CH2Cl2 solution where the isomerization rate is very fast for the Ni, intermediate for the Pd, and very slow for the Pt species. It is shown that the electronic structures of 1a/1b, 2a/2b, 3a, and 3b are best described as diradicals with a singlet ground state. The spectro- and electrochemistries of all complexes display the usual full electron transfer series where the monocation, the neutral species, the mono- and dianions have been spectroscopically characterized. X-band EPR spectra of the monocations [1a/1b]+ and [3a]+ support the assignment of an oxidation-state distribution as predominantly [M(II)(L(ISQ))(L(IBQ))]+ where (L(IBQ))0 represents the o-iminothionequinone level. In contrast, the EPR spectra of the monoanions [1a/1b]- and [3a]- indicate an [M(II)(L(ISQ))(L(AP)-H)]- distribution but with a significant contribution of the [M(I)(L(ISQ))(2)]- resonance hybrid; (L(AP)-H)2- represents the o-imidothiophenolato(2-) oxidation level. Analysis of the geometric features of 120 published structures of complexes containing ligands of the o-aminothiophenolate type show that high precision X-ray crystallography allows to discern the differing protonation and oxidation levels of these ligands. o-Aminothiophenolates are unequivocally shown to be noninnocent ligands; the (L(ISQ))1- radical form is quite prevalent in coordination compounds and the electronic structure of a number of published complexes must be reconsidered.

Effect of solvent on the inversion of pyramidal sulfonium and selenonium compounds

AbstractThe effects of temperature and solvent on the cis–trans equilibrium and isomerization rates of different cyclic sulfonium and selenonium compounds were investigated by 1H NMR spectroscopy. A non‐dissociative process was considered to be the most probable mechanism for inversion of configuration. While the temperature had no apparent effect on the equilibrium, in which the trans‐diastereoisomer dominated in all cases, changing the solvent from dimethylformamide to acetonitrile and to water led to increasing amounts of the cis‐diastereoisomer. Additionally, the rate of stereomutation of the thiolanium compound was slowed by a factor of 2 and that of the selenolanium compound by a factor of 85. While the pyramidal (vertex) inversion is the most probable mechanism for the sulfonium compounds investigated, some evidence is presented that indicates that the selenonium compound could isomerize via an edge inversion mechanism. Copyright © 2001 John Wiley &amp; Sons, Ltd.

Why Does the Tetrakis(trimethylphosphine)iridium(III) Hydridochloride Cation Adopt the Sterically and Electronically Unfavorable Cis Geometry?

Although the tetrakis(trimethylphosphine)iridium(III) hydridochloride cation, [HIrCl(PMe3)4]+, and similar complexes would intuitively be expected to adopt a trans geometry on electronic and sterical grounds, experimentally the cis geometry is found to prevail. Quantum chemical calculations suggest that the trans and cis structures are nearly isoenergetic, such that the cis:trans equilibrium is dominated by the higher entropy of the lower symmetry cis structure.

Structures of the Contryphan Family of Cyclic Peptides. Role of Electrostatic Interactions in cis−trans Isomerism,

The contryphan family of cyclic peptides, isolated recently from various species of cone shell, has the conserved sequence motif NH(3)(+)-X(1)COD-WX(5)PWC-NH(2), where X(1) is either Gly or absent, O is 4-trans-hydroxyproline, and X(5) is Glu, Asp, or Gln. The solution structures described herein of two new naturally occurring contryphan sequences, contryphan-Sm and des[Gly1]-contryphan-R, are similar to those of contryphan-R, the structure of which has been determined recently [Pallaghy et al. (1999) Biochemistry 38, 11553-11559]. The (1)H NMR chemical shifts of another naturally occurring peptide, contryphan-P, indicate that it also adopts a similar structure. All of these contryphans exist in solution as a mixture of two conformers due to cis-trans isomerization about the Cys2-Hyp3 peptide bond. The lower cis-trans ratio for contryphan-Sm enabled elucidation of the 3D structure of both its major and its minor forms, for which the patterns of (3)J(H)(alpha)(HN) coupling constants are very different. As with contryphan-R, the structure of the major form of contryphan-Sm (cis Cys2-Hyp3 peptide bond) contains an N-terminal chain reversal and a C-terminal type I beta-turn. The minor conformer (trans peptide bond) forms a hairpin structure with sheetlike hydrogen bonds and a type II beta-turn, with the D-Trp4 at the 'Gly position' of the turn. The ratio of conformers arising from cis-trans isomerism around the peptide bond preceding Hyp3 is sensitive to both the amino acid sequence and the solution conditions, varying from 2.7:1 to 17:1 across the five sequences. The sequence and structural determinants of the cis-trans isomerism have been elucidated by comparison of the cis-trans ratios for these peptides with those for contryphan-R and an N-acetylated derivative thereof. The cis-trans ratio is reduced for peptides in which either the charged N-terminal ammonium or the X(5) side-chain carboxylate is neutralized, implying that an electrostatic interaction between these groups stabilizes the cis conformer relative to the trans. These results on the structures and cis-trans equilibrium of different conformers suggest a paradigm of 'locally determined but globally selected' folding for cyclic peptides and constrained protein loops, where the series of stereochemical centers in the loop dictates the favorable conformations and the equilibrium is determined by a small number of side-chain interactions.

NMR studies of transformations of aminoacid complexes of Pt(II) and Pd(II) in solution. 2. Bisalaninates

Synthetic procedures are suggested for diastereomers of Pt(II) and Pd(II) bischelates with alanine: cis- and trans-Pt(l-Ala)2 , trans-Pt(l-Ala)fd-Ala), trans-Pd(l-Ala)2 , and trans-Pd(l-Ala)(d-AIa). Methods of their isolation in individual solid state are proposed.1H,13C, and195Pt NMR spectral investigations are reported for the individual diastereomers and for M(Ala)2 racemates in DMSO solution. The trans-isomers of Pd(II) bisalaninates in DMSO solution are transformed into an equilibrium mixture of cis- and trans-isomers. For Pt(II) complexes, the cis ↔ trans equilibrium was also found but the equilibration rate is much lower than that for Pd(II) bischelates for both cis- and trans-isomer. An equilibrium 2M(l-Ala)(d-Ala) ⇌ M(l-Ala)2+M(d-Ala)2 is also shown to exist.

NMR studies of transformations of Pt(II) and Pd(II) complexes with amino acids in solution. 1. Glycine complexes

1H,13C, and195Pt NMR studies were performed for Pt(ll) and Pd(II) complexes with glycine cis- and trans-M(Gly)2, trans-Pd(GlyH)2Cl2 , cis- and trans-Pt(GlyH)2Cl2 , Na[Pd(GIy)Cl2], and K[Pt(Gly)CI2] in donor type solvents DMSO and H2O. It is shown that a cis ↔ trans equilibrium takes place in these solvents and that the equilibration rate is low for Pt(II) complexes and high for Pd(II) complexes. Therefore, the cis- and trans-complexes of Pt(II) may be recorded by NMR spectroscopy in the individual state, whereas for Pd(II) there is an equilibrium mixture of cis- and trans-isomers. Solvolysis of Cl-containing complexes in DMSO is studied. A mechanism of solvolysis involving eis ↔ trans isomerization of the dichloro complexes of Pd(II) is suggested. NMR spectral data for some solvolysis products are given.

Conformational analysis of dimethyl phosphate in aqueous solution: a density functional theory-based molecular dynamics study

The conformational flexibility of the phosphodimethyl ester in aqueous solution at room temperature is explored using density functional theory-based molecular dynamics calculations. The system comprises protonated dimethyl phosphate and 32 water molecules. In spite of the very short time scale investigated (2.2 ps), the simulation provides evidence that solvent reorganization plays an important role in the transition between gauche, gauche and gauche, trans equilibrium conformations.

Potential energy function and vibrational states of N2CO+

A six-dimensional potential energy function (PEF) for the electronic ground state of N2CO+ (X 2A′) has been generated by electronic structure calculations using the restricted open shell coupled cluster RCCSD(T) approach. The ion has a planar trans equilibrium structure with: RNN=1.106 Å, RNC=1.905 Å, RCO=1.127Å, θNNC=175.3°, and θNCO=129.1°. Variational calculations of the vibrational states (J=0) have yielded the following anharmonic wavenumbers for the fundamentals: ν1 (NN stretch) 2287.2, ν2 (CO stretch) 2071.0, ν3 (CN stretch+NCO bend) 546.9, ν4 (CN stretch+NCO bend) 215.2, ν5 (in-plane NNC bend) 123.4, ν6 (out-of-plane NNC bend) 133.8 (all values are in cm−1). For fixed equilibrium coordinates except one, the barriers to linearity have been calculated to be 8 cm−1 for the NNC and 2260 cm−1 for the NCO moieties, the torsional barrier to be 35 cm−1. It has been found that the ν3 and ν4 modes are strongly coupled, the in-plane ν5 and out-of-plane ν6 bending modes possess an inverse anharmonicity and fall into clusters. Using complete active space self-consitent-field CASSCF approach on the collinear cuts of the PEF for low-lying excited states several conical intersections between the Π2 and the Σ+2 states have been located.

Investigations on a flexible prolyl-endopeptidase inhibitor in solution by NMR techniques

4-Phenylbutyrylprolylpyrrolidine, an inhibitor of prolyl-endopeptidase, exists in solution as an equilibrium of trans and cis prolyl rotamers. The equilibrium ratio and the exchange rate of the rotamers were measured in several solvents. The conformational preferences of the flexible molecule were studied by NMR, based on proton–proton vicinal coupling constants, NOESY cross peak intensities and aromatic ring current shifts. Copyright  1999 John Wiley & Sons, Ltd.

Synthesis, reactions and X-ray crystal structures of metallacrown ethers with unsymmetrical bis(phosphinite) and bis(phosphite) ligands derived from 2-hydroxy-2′-(1,4-bisoxo-6-hexanol)-1,1′-biphenyl

Chlorodiphenylphosphine and 2,2′-biphenylylenephosphorochloridite react with 2-hydroxy-2′-(1,4-bisoxo-6-hexanol)-1,1′-biphenyl to yield the new α,ω-bis(phosphorus-donor)-polyether ligands, 2-Ph2PO(CH2CH2O)2–C12H8-2′-OPPh2 (1) and 2-(2,2′-O2C12H8)P(CH2CH2O)2–C12H8-2′-P(2,2′-O2C12H8) (2). These ligands react with Mo(CO)4(nbd) to form the monomeric metallacrown ethers, cis-Mo(CO)4{2-Ph2PO(CH2CH2O)2–C12H8-2′-OPPh2} (cis-3) and cis-Mo(CO)4{2-(2,2′-O2C12H8)P(CH2CH2O)2–C12H8-2′-P(2,2′-O2C12H8)} (cis-4), in good yields. The X-ray crystal structures of cis-3 and cis-4 are significantly different, especially in the conformation of the metal center and the adjacent ethylene group. The very different 13C-NMR coordination chemical shifts of this ethylene group in cis-3 and cis-4 suggest that the solution conformations of these metallacrown ethers are also quite different. Both metallacrown ethers undergo cis–trans isomerization in the presence of HgCl2. Although the cis–trans equilibrium constants for the isomerization reactions are nearly identical, the isomerization of cis-3 is more rapid. Phenyl lithium reacts with cis-3 to form the corresponding benzoyl complexes but does not react with either trans-3 or cis-4. Both the slower rate of cis–trans isomerization of cis-4 and its lack of reaction with PhLi are consistent with weaker interactions between the hard metal cations and the carbonyl oxygens in both trans-3 and cis-4.

Reversible Polymerization and Cis−Trans Isomerization Equilibria in [PdCl2{Ph2P(CH2CH2O)4CH2CH2PPh2-P,P‘}] Metallacrown Ethers

The first study of metallacrown ethers with kinetically labile metal centers is reported. The reaction of Ph2P(CH2CH2O)4CH2CH2PPh2 with PdCl2 in an acetonitrile−dichloromethane solution yields an equilibrium mixture of cyclic n-mers and monomers with the empirical formula [PdCl2{Ph2P(CH2CH2O)4CH2CH2PPh2-P,P‘}]. Both cis and trans coordination geometries are observed for the palladium(II) in these complexes, with the trans being the more abundant. The solution equilibria in both chloroform-d and acetonitrile-d3 were studied using 31P{1H}, 13C{1H}, and 1H NMR spectroscopy. A model has been developed relating the product distributions at various concentrations, obtained from integration of quantitative 31P{1H} NMR spectra, to a cis−trans equilibrium constant and equilibrium constants for the dimerization and n-merization reactions of the trans monomer. The concentration and temperature dependence of the equilibrium constants obtained from this model are consistent with the thermodynamics of cis−trans isomeri...

Synthesis and structure of 4-X-chalcones

This study examines two formation mechanisms of 4-X-chalcones by alkaline condensation of acetophenone and p-X-benzaldehydes ( X = H, OH, N(CH 3) 2, F, Cl, OCH 3, NH 2 and CH 3) and the structures and trans-s- cis ⇔ trans-s- trans conformational equilibrium of these 4-X-chalcones. The calculations are performed with the semiempirical method AM1, using totally optimized molecular geometries. It is concluded that: 1. (a) intermediary 2 is more likely to be obtained by mechanism II than by mechanism I; 2. (b) step (a) of mechanism II satisfactorily accounts for the yield of 4-X-chalcones formation; 3. (c) reaction mechanism II is much more likely than mechanism I; 4. (d) the rate of 4-X-chalcones formation varies with the substituent in the order N(( CH 3) 2 ≅ NH 2 > OH ≅ OCH 3 > F > CH 3 > Cl = H; 5. (e) although trans-s- cis structures are the most stable ones, trans-s- trans forms also show acceptable thermodynamic stability; 6. (f) in the t-s- cis ⇔ t-s- trans equilibrium, the percentages of the t-s- cis conformer at 298 K range between 37% and 82% approximately.

Surface-Enhanced Raman Scattering (SERS) Study of Mercaptoethanol Monolayer Assemblies on Silver Citrate Hydrosol. Preparation and Characterization of Modified Hydrosol as a SERS-Active Substrate

The self-assembling technique was employed for modification of a citrate-reduced silver hydrosol with mercaptoethanol (ME). The results of investigation of the structure and properties of both the self-assembled monolayers (SAMs) of ME and the modified hydrosol as a substrate for surface-enhanced Raman scattering (SERS) spectroscopy are presented. ME chemisorbs on the hydrosol by rupture of the S−H bond with concomitant bonding of the sulfur headgroup to Ag. Chemisorption is accompanied by gauche−trans isomerization of ME. The isomerization occurs cooperatively at submonolayer coverage due to interactions of neighboring adsorbed molecules rather than due to the chemisorption itself. The chemisorption of ME takes place on a less than 5 min time scale and leads to formation of a SAM with definite density and gauche−trans equilibrium, the parameters of which depend on the bulk concentration of ME but not on the time of incubation. It was revealed that densely packed and highly ordered (97% of trans-isomers) SAM is formed at an ME concentration higher than 250 μM. ME induces concentration-dependent aggregation of the hydrosol and makes it SERS active. After 30 min of incubation with 250 μM ME the modified hydrosol has the highest Raman enhancement only slightly altered during the next 40−50 min. Preactivation of the hydrosol surface with ClO4-, NO3-, Cl-, Br-, and I- anions does not improve SAM formation or Raman enhancement. Using β-carotene as a probe molecule it was well demonstrated that the structured surface of the modified hydrosol provides favorable conditions for increasing the number of adsorption sites and increasing the adsorption constant for an analyte. It also protects an analyte from direct contact with the metal surface, thereby preventing distortion of the electronic system of adsorbed molecule. These advantages make the modified hydrosol a useful tool for SERS probing of chromophores with intense electronic transitions in the visible region.

Remarkably slow folding of a small protein

Equilibrium denaturation of the 72 amino acid α/β-protein MerP, by acid, guanidine hydrochloride, or temperature, is fully reversible and follows a two-state model in which only the native and unfolded states are populated. A cis- trans equilibrium around a proline peptide bond causes a heterogeneity of the unfolded state and gives rise to a slow- and a fast folding population. With a rate constant of 1.2 s −1 for the major fast folding population, which has none of the common intrinsically slow steps, MerP is the slowest folding protein of this small size yet reported.

Cationic Zirconium Dialkyl and Alkyl Complexes Supported by DAC (Deprotonated 4,13-Diaza-18-crown-6) Ligation

The synthesis, characterization, and reactivity of a series of neutral and cationic Zr alkyls supported by DAC (deprotonated 4,13-diaza-18-crown-6) ligation are reported. Reaction of H2DAC with Zr(CH2Ph)4 affords a 1:4 mixture of cis- and trans-Zr(DAC)(CH2Ph)2 (cis-/trans-1a). The pure isomers undergo slow cis−trans isomerization in solution to regenerate the 1:4 cis:trans equilibrium mixture. X-ray crystallographic results are reported for both cis- and trans-1a. Reaction of Zr(CH2Ph)2Cl2 with H2DAC, followed by treatment with LiR (2 equiv), gives cis-Zr(DAC)R2 (R = CH2SiMe3, cis-1b; R = CH2CMe3, cis-1c) exclusively. Alkyl abstraction from cis- or trans-1a using B(C6F5)3 (1 equiv) produces the stable cation [Zr(DAC)(CH2Ph)]+[B(CH2Ph)(C6F5)3]- (2a) as a yellow oil. NMR studies on 2a in CD2Cl2 show no evidence for η2-benzyl formation or anion coordination. Protonation of cis- or trans-1a with [n-Bu3NH]+[BPh4]- similarly yields [Zr(DAC)(CH2Ph)]+[BPh4]- (2b). Cation 2a reacts with t-BuNC to form the vinyl amide complex [Zr(DAC){N(t-Bu)CHCHPh}]+[B(CH2Ph)(C6F5)3]- (3). p-Tolylacetylene undergoes catalytic dimerization to (Z)-1,4-di-p-tolyl-1-buten-3-yne in the presence of 2a.