Synthesis of beta-lactams from a N-rhenaimine: effect of the transition metal on the energetic profile of the Staudinger reaction

As depicted in the scheme, the alkylidenamido complex 1, a N-rhenaimine, reacts with ketenes to afford the beta-lactams 2-4, which possess a {Re(CO)3(bpy)} fragment as substituent at nitrogen. Clean demetalations using HOTf or MeOTf yield the free beta-lactams or N-methyl-beta-lactams along with [Re(OTf)(CO)3(bpy)]. DFT calculations help to rationalize why the reaction is faster than those of non transition metal N-substituted imines.     

Binary and Ternary Complexes Between Lauryl Hexaoxyethylene, Benzoate and Cyclodextrin. Part II. β-CD

The characterization of binary and ternary complexes of benzoate, lauryl hexaoxyethylene (C₁₂E₆) and -CD is presented. The complexation equilibrium was characterized by UV-Vis spectrophotometry, titration microcalorimetry, capillary electrophoresis, and 2D ROESY ¹H-NMR. Results suggested that -CD forms one complex with C₁₂E₆in the stoichiometric ratio of -CD : C₁₂E₆1.5 : 1, with a stability constant 1.3 × 10⁵ M^-1.5. The 2-D ROESY ¹H-NMR spectrum indicated that C₁₂E₆is included inside the -CD cavity. The primary binding site of C₁₂E₆ is on the lauryl subunit of this molecule. Analogous to a previously reported study of -CD, the combination of -CD and C₁₂E₆precipitated from the solution. Addition of benzoate seemed to dissolve the precipitate and nearly doubled the apparent stability constant of the complex. Results from the various techniques supported formation of ternary complexes between -CD, C₁₂E₆, and benzoate.     

Capture of toxic gases in MOFs: SO2, H2S,NH3 and NOx

MOFs are promising candidates for the capture of toxic gases since their adsorption properties can be tuned as a function of the topology and chemical composition of the pores. Although the main drawback of MOFs is their vulnerability to these highly corrosive gases which can compromise their chemical stability, remarkable examples have demonstrated high chemical stability to SO₂, H₂S, NH₃ and NO_x. Understanding the role of different chemical functionalities, within the pores of MOFs, is the key for accomplishing superior captures of these toxic gases. Thus, the interactions of such functional groups (coordinatively unsaturated metal sites, μ-OH groups, defective sites and halogen groups) with these toxic molecules, not only determines the capture properties of MOFs, but also can provide a guideline for the desigh of new multi-functionalised MOF materials. Thus, this perspective aims to provide valuable information on the significant progress on this environmental-remediation field, which could inspire more investigators to provide more and novel research on such challenging task.

MOFs are promising candidates for the capture of toxic gases such as SO₂, H₂S, NH₃ and NOx. Understanding the role of different chemical functionalities, within the pores of MOFs, is the key for accomplishing superior captures of these toxic gases.     

Glycosylation site analysis of human alpha-1-acid glycoprotein (AGP) by capillary liquid chromatography-electrospray mass spectrometry

A new anionic surfactant (RapiGest SF) was successfully used for site-specific analysis of glycosylation in human alpha-1-acid glycoprotein (AGP). By means of this analytical approach combined with capillary HPLC-mass spectrometry (and tandem mass spectrometry), the N-linked glycosylation pattern of AGP was explored. On the basis of mass matching and MS/MS experiments ca 80 different AGP-derived glycopeptides were identified. Glycosylation shows a markedly different pattern for the various glycosylation sites. At sites I and II, triantennary complex-type oligosaccharides predominate and at sites III, IV and V, tetra-antennary complex-type oligosaccharides predominate. Sites IV and V show the presence of additional N-acetyl lactosamine (Gal-GlcNAc) units (even higher degree of branching and/or longer antennae are also present).     

Dynamic NMR properties of DOTA ligand: variable pH and temperature 1H NMR study on [K(HxDOTA)](3-x)- species

The (1)H NMR spectra of [H(x)DOTA]((4-x)-) species are reported as a function of pH and temperature in aqueous solution. The spectra show line broadening both in ligand proton signals and also in the water proton signal by titration with KOH solution. The formation of different [K(H(x)DOTA)]((3-x)-) complexes is found to be responsible for this behaviour. At high pH the usual fluxional motions, i.e. the ring inversion and the change in the acetate arms' helicity, which are also characteristic for other but inert metal-DOTA complexes, have been detected. However, because of the kinetic lability of K(+)-O and K(+)-N coordinative bonds a new type of rearrangement appears. This new motion requires breaking of coordinative bonds in the complex and can be described as a certain type of "ring slewing" around the ring C-C bonds. At low temperature (about 270 K) the ring slewing slows down and becomes negligible compared with the ring inversion and the change in the arms' helicity. These two latter processes have the same rate. When the temperature is higher (about 320 K) the ring slewing accelerates and its rate exceeds the rate of ring inversion. At this temperature the change in the acetate arms' helicity has the same rate as the ring slewing. Additionally, in the pH range 4-5 a slow intermolecular proton exchange process has been observed between the water and the dissociable protons of [K(H(x)DOTA)]((3-x)-). A water-assisted proton exchange mechanism is proposed on the basis of the activation parameters. This finding supports the previously suggested slow proton motion hypothesis for the formation of DOTA complexes.     

Carbohydrate-based DNA ligands: sugar-oligoamides as a tool to study carbohydrate-nucleic acid interactions

Sugar-oligoamides have been designed and synthesized as structurally simple carbohydrate-based ligands to study carbohydrate-DNA interactions. The general design of the ligands 1-3 has been done as to favor the bound conformation of Distamycin-type gamma-linked covalent dimers which is a hairpin conformation. Indeed, NMR analysis of the sugar-oligoamides in the free state has indicated the presence of a percentage of a hairpin conformation in aqueous solution. The DNA binding activity of compounds 1-3 was confirmed by calf thymus DNA (ct-DNA) NMR titration. Interestingly, the binding of the different sugar-oligoamides seems to be modulated by the sugar configuration. Semiquantitative structural information about the DNA ligand complexes has been derived from NMR data. A competition experiment with Netropsin suggested that the sugar-oligoamide 3 bind to DNA in the minor groove. The NMR titrations of 1-3 with poly(dA-dT) and poly(dG-dC) suggested preferential binding to the ATAT sequence. TR-NOE NMR experiments for the sugar-oligoamide 3-ct-DNA complex both in D(2)O and H(2)O have confirmed the complex formation and given information on the conformation of the ligand in the bound state. The data confirmed that the sugar-oligoamide ligand is a hairpin in the bound state. Even more relevant to our goal, structural information on the conformation around the N-glycosidic linkage has been accessed. Thus, the sugar asymmetric centers pointing to the NH-amide and N-methyl rims of the molecule have been characterized.     

Fine-tuning water exchange on Gd(III) poly(amino carboxylates) by modulation of steric crowding

In the objective of optimizing water exchange rate on stable, nine-coordinate, monohydrated Gd(III) poly(amino carboxylate) complexes, we have prepared monopropionate derivatives of DOTA4- (DO3A-Nprop4-) and DTPA5- (DTTA-Nprop5-). A novel ligand, EPTPA-BAA(3-), the bisamylamide derivative of ethylenepropylenetriamine-pentaacetate (EPTPA5-) was also synthesized. A variable temperature 17O NMR study has been performed on their Gd(III) complexes, which, for [Gd(DTTA-Nprop)(H2O)]2- and [Gd(EPTPA-BAA)(H2O)] has been combined with multiple field EPR and NMRD measurements. The water exchange rates, k(ex)(298), are 8.0 x 10(7) s(-1), 6.1 x 10(7) s(-1) and 5.7 x 10(7) s(-1) for [Gd(DTTA-Nprop)(H2O)]2-, [Gd(DO3A-Nprop)(H2O)]- and [Gd(EPTPA-BAA)(H2O)], respectively, all in the narrow optimal range to attain maximum proton relaxivities, provided the other parameters (electronic relaxation and rotation) are also optimized. The substitution of an acetate with a propionate arm in DTPA5- or DOTA4- induces increased steric compression around the water binding site and thus leads to an accelerated water exchange on the Gd(III) complex. The k(ex) values on the propionate complexes are, however, lower than those obtained for [Gd(EPTPA)(H2O)]2- and [Gd(TRITA)(H2O)]- which contain one additional CH(2) unit in the amine backbone as compared to the parent [Gd(DTPA)(H2O)]2- and [Gd(DOTA)(H2O)]-. In addition to their optimal water exchange rate, [Gd(DTTA-Nprop)(H2O)]2- has, and [Gd(DO3A-Nprop)(H2O)]- is expected to have sufficient thermodynamic stability. These properties together make them prime candidates for the development of high relaxivity, macromolecular MRI contrast agents.     

2‐(4‐Hydroxy­phenyl)‐4,4‐dimethyl‐2‐oxazoline: X‐ray and density functional theory study

In the crystal structure of the title compound, C₁₁H₁₃NO₂, there are strong inter­molecular O—H⋯N hydrogen bonds which, together with weak intra­molecular C—H⋯O hydrogen bonds, lead to the formation of infinite chains of mol­ecules, held together by weak inter­molecular C—H⋯O hydrogen bonds. A theoretical investigation of the hydrogen bonding, based on density functional theory (DFT) employing periodic boundary conditions, is in agreement with the experimental data. The cluster approach shows that the influence of the crystal field and of hydrogen‐bond formation are responsible for the deformation of the 2‐oxazoline ring, which is not planar and adopts a ⁴T₃ (^C3T_C2) conformation.     

Derivatives of benzo[5,6]cyclohepta[1,2-b]thiophene. Synthesis of 2,3,7,8-tetrahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline and 1,2,3,7,8,11b-hexahydro-3-oxothieno[1,2-b]cyclohepta[5,6,7-de]isoquinoline

The synthesis of the title compounds was carried out by cyclization via isocyanate of (E)-4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylideneacetic acid and 4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]-thiophene-10-ylacetic acid respectively, which were obtained by the Wadsworth-Emmons modification of the Wittig reaction of 4,5-dihydro-10H-10-oxobenzo[5,6]cyclohepta[1,2-b]thiophene and triethyl phosphonacetate. The structures of these new compounds are described.