X-ray absorption spectroscopies: useful tools to understand metallorganic frameworks structure and reactivity

The large unit cells, the enormous flexibility and variation in structural motifs of MOFs represent a big challenge in the characterization of MOF materials, particularly in cases where single crystal diffraction data are not available. In this critical review it is shown that in cases where only powder diffraction data are available additional structural information, particularly regarding local coordination within the inorganic cluster, are often mandatory in order to solve the structure. There are also cases where the inorganic cluster does not follow the symmetry of the overall structure. In such cases diffraction techniques will just "see" an average structure, missing the local structure: a lack that may be critical for understanding the specific properties of the material. In both cases, EXAFS spectroscopy is the tool that provides complementary structural information on the inorganic cluster and the way it binds to the ligand. Selected examples will show how EXAFS will be relevant in: (i) confirming the structure obtained from diffraction refinements; (ii) highlighting that the inorganic cornerstone has a lower symmetry with respect to that of the organic framework; (iii) obtaining the local structure of the inorganic cluster in the desolvated material when desolvation causes a partial loss of long range order; (iv) obtaining the local structure of the inorganic cluster in the desolvated material after coordination of a probe (or reactant) molecule, including cluster deformation upon molecule coordination and metal-molecule binding distance; (v) evidencing the presence of impurities in the form of amorphous extra-phases (339 references).     

Insights into the Dynamics and Molecular Recognition Features of Glycopeptides by Protein Receptors: The 3D Solution Structure of Hevein Bound to the Trisaccharide Core of N‐Glycoproteins

Protein‐carbohydrate interactions are at the heart of a variety of essential molecular recognition events. Hevein, a model lectin related to the superantigen family, recognizes the trisaccharide core of N‐glycoproteins ( 1 ). A combined approach of NMR spectroscopy and molecular modeling has permitted us to demonstrate that an Asn‐linked Man(GlcNAc)₂ ( 2 ) is bound with even higher affinity than (GlcNAc)₃. The molecular recognition process entails conformational selection of only one of the possibilities existing for chitooligosaccharides. The deduced 3D structure of the hevein/ 2 complex permits the extension of polypeptide chains from the Asn moiety of 2 , as well as glycosylation at Man O‐3 and Man O‐6 of the terminal sugar. Given the ubiquity of the Man(GlcNAc)₂ core in all mammalian N‐glycoproteins, the basic recognition mode presented herein might be extended to a variety of systems with biomedical importance.     

Solid-state (15)N CPMAS NMR and computational analysis of ligand hapticity in rhodium(η-diene) poly(pyrazolyl)borate complexes

Novel [Rh(η-diene)Tp(x)] complexes of sterically encumbered Tp(x) ligands (Tp(x) = Tp(4Bo), diene = cod, 1; nbd, 2; Tp(x) = Tp(4Bo,5Me), diene = cod, 3; nbd, 4; Tp(x) = Tp(a,3Me), diene = cod, 5; nbd, 6; Tp(x) = Tp(a*,3Me), diene = cod, 7; nbd, 8) have been prepared by treatment of [Rh(η-diene)(μ-Cl)](2) with TlTp(x) (Tp(x) in general, in detail: Tp(4Bo) = hydrotris(indazol-1-yl)borate, Tp(4Bo,5Me) = hydrotris(5-methyl-indazol-1-yl)borate, Tp(a,3Me) = hydrotris(3-methyl-2H-benz[g]-4,5-dihydroindazol-2-y1)borate, Tp(a*,3Me) = hydrotris(3-methyl-2H-benz[g]indazol-2-yl)borate), and characterized by analytical and spectral data (IR, (1)H, (11)B, and (13)C NMR solution). The structures adopted by [Rh(nbd)Tp(4Bo)] 2, [Rh(cod)Tp(4Bo,5Me)] 3, [Rh(nbd)Tp(a,3Me)] 6, [Rh(nbd)Tp(a*,3Me)] 8, and [Rh(nbd)Tp(a*,3Me*)] 8* (incorporating a borotropomeric ligand), have been investigated. Low steric hindrance between the ligands in 2 and 3 permits κ(3) coordination of the pyrazolylborate while the high steric encumbrance present in 6, 8, and 8* results in κ(2) ligands. The coordination modes of the ligands to the metal have also been established by (15)N CPMAS studies of selected ligands and their corresponding Rh complexes. These spectroscopic data are in agreement with the (15)N chemical shifts obtained by using quantum-chemical methods to assist reliable assignments of the experimental values, affording new insights into the extraction of structural information concerning the hapticity (κ(2) or κ(3)) of the poly(pyrazolyl)borate ligands to the Rh metal.     

Photo-induced pyridine substitution in cis-[Ru(bpy)(2)(py)(2)]Cl(2): a snapshot by time-resolved X-ray solution scattering

Determination of transient structures in light-induced processes is a challenging goal for time-resolved techniques. Such techniques are becoming successful in detecting ultrafast structural changes in molecules and do not require the presence of probe-like groups. Here, we demonstrate that TR-WAXS (Time-Resolved Wide Angle X-ray Scattering) can be successfully employed to study the photochemistry of cis-[Ru(bpy)(2)(py)(2)]Cl(2), a mononuclear ruthenium complex of interest in the field of photoactivatable anticancer agents. TR-WAXS is able to detect the release of a pyridine ligand and the coordination of a solvent molecule on a faster timescale than 800 ns of laser excitation. The direct measurement of the photodissociation of pyridine is a major advance in the field of time-resolved techniques allowing detection, for the first time, of the release of a multiatomic ligand formed by low Z atoms. These data demonstrate that TR-WAXS is a powerful technique for studying rapid ligand substitution processes involving photoactive metal complexes of biological interest.     

Regioselective reduction of 3-substituted 2,3-dihydrobenzothiadiazines with borohydrides

A simple and efficient synthetic path for N-1 or N-2 alkyl-substituted 2-aminobenzenesulfonamides was developed based on regioselective reduction with NaBH₃CN in different solvents.     

Investigation of gaseous metabolites from moulds by Ion Mobility Spectrometry (IMS) and Gas Chromatography-Mass Spectrometry (GC-MS)

The metabolism of moulds results in the formation of various microbial volatile organic compounds (MVOCs). These substances can be used as an indicator for the presence of moulds in the indoor environment. Three different mould strains were cultivated on culture media and IMS spectra of gaseous mould metabolites were recorded using a portable mini system with a tritium source and a 5 cm drift cell. The headspace spectra are characteristic for mould species and their age. Typical gaseous components of the metabolites were identified and compared with results obtained from gas chromatography using a mass spectrometer detector. It was observed that the MVOCs formation depends on mould species and their growing stage with a maximum of MVOCs emission occurring during the first 10 days. These preliminary results show that IMS can be applied to detect MVOCs in indoor environment and indicate hidden mould growth.     

Gold(III) six-membered N^C^N pincer complexes: synthesis, structure, reactivity and theoretical calculations

The first six-membered gold(III) N^C^N pincer complex was obtained in good yield, under very mild conditions, by transmetalation of [Hg(κC-N^C^N)Cl] (N^CH^N = 1,3-bis(pyridin-2-ylmethyl)benzene, HL(1)) with Na[AuCl(4)]. The X-ray crystal structure of [Au(N^C^N)Cl][PF(6)] showed that the fused six-membered metallacycles each exist in a strongly puckered boat conformation. As shown by the (1)H NMR spectra in various solvents, the same structure is also retained in solution: no inversion of the six-membered metallacycles is observed in DMSO up to 95 °C. This correlates well with a reaction barrier of 17.5 kcal/mole, as determined by quantum chemical calculations. The reactivity of the present pincer complex is compared to that of the analogous 1,3-bis(2-pyridyl)benzene, HL(2), derivative, which has five-membered fused metallacycles. Sharp differences are found in the reactions with phosphines, such as PPh(3) and dppe (1,2-bis-diphenylphosphino-ethane), and with silver salts. Theoretical calculations were carried out on the two pincer complexes in order to try to understand these differences, and we found that the gold-chlorine bond is significantly stronger in the case of the complex containing five-membered metallacyclic rings.     

Circular dichroism in drug discovery and development: an abridged review

Chirality plays a fundamental role in determining the pharmacodynamic and pharmacokinetic properties of drugs, and contributes significantly to our understanding of the mechanisms that lie behind biorecognition phenomena. Circular dichroism spectroscopy is the technique of choice for determining the stereochemistry of chiral drugs and proteins, and for monitoring and characterizing molecular recognition phenomena in solution. The role of chirality in our understanding of recognition phenomena at the molecular level is discussed here via several selected systems of interest in the drug discovery and development area. The examples were selected in order to underline the utility of circular dichroism in emerging studies of protein–protein interactions in biological context. In particular, the following aspects are discussed here: the relationship between stereochemistry and pharmacological activity—stereochemical characterization of new leads and drugs; stereoselective binding of leads and drugs to target proteins—the binding of drugs to serum albumins; conformational transitions of peptides and proteins of physiological relevance, and the stereochemical characterization of therapeutic peptides.     

Structural Analysis of a Helical Peptide Unfolding Pathway

The analysis of the folding mechanism in peptides adopting well‐defined secondary structure is fundamental to understand protein folding. Herein, we describe the thermal unfolding of a 15‐mer vascular endothelial growth factor mimicking α‐helical peptide (QK_L10A) through the combination of spectroscopic and computational analyses. In particular, on the basis of the temperature dependencies of QK_L10A H_α chemical shifts we show that the first phase of the thermal helix unfolding, ending at around 320 K, involves mainly the terminal regions. A second phase of the transition, ending at around 333 K, comprises the central helical region of the peptide. The determination of high‐resolution QK_L10A conformational preferences in water at 313 K allowed us to identify, at atomic resolution, one intermediate of the folding–unfolding pathway. Molecular dynamics simulations corroborate experimental observations detecting a stable central helical turn, which represents the most probable site for the helix nucleation in the folding direction. The data presented herein allows us to draw a folding–unfolding picture for the small peptide QK_L10A compatible with the nucleation–propagation model. This study, besides contributing to the basic field of peptide helix folding, is useful to gain an insight into the design of stable helical peptides, which could find applications as molecular scaffolds to target protein–protein interactions.