Co(ii)-induced giant vibrational CD provides a new design of methods for rapid and sensitive chirality recognition.

We designed a stereodynamic system, where the chirality of the analyte serves as a template for the helicity of the first coordination sphere of Co(ii). Giant VCD bands induced by Co(ii) allow the measurement of a completely significant and conclusive VCD spectrum in only a few seconds and/or on minute quantities of the analyte. This paves the way for the development of similar protocols, overcoming the limitations due to weak VCD signals for the assignment of absolute configurations.

The folding of a metallopeptide.

We have applied solid-phase synthesis methods for the construction of tris(bipyridyl) peptidic ligands that coordinate Fe(ii) ions with high affinity and fold into stable mononuclear metallopeptides. The main factors influencing the folding pathway and chiral control of the peptidic ligands around the metal ions have been studied both by experimental techniques (CD, UV-vis and NMR) and molecular modeling tools. Amongst the numerous molecular variables that have been studied, this study clearly illustrates how the chirality of a given set of aminoacids (proline in this case) of the peptide dictates the chirality of the metal center of the resulting metallopeptide. Moreover, the relatively hydrophobic peptidic models used in this work show that the most stable structures present reduced solvent contacts and, in counterpart, stabilize the cis configuration of the proline residues.

Chirality at metal and helical ligand folding in optical isomers of chiral bis(naphthaldiminato)nickel(II) complexes.

Enantiopure bis[{(R or S)-N-1-(Ar)ethyl-2-oxo-1-naphthaldiminato-κ(2)N,O}]nickel(ii) complexes {Ar = C6H5 ( or ), p-OMeC6H4 ( or ), and p-BrC6H4 ( or )} are synthesized from the reactions between (R or S)-N-1-(Ar)ethyl-2-oxo-1-naphthaldimine and nickel(ii) acetate. Circular-dichroism spectra and their density-functional theoretical simulation reveal the expected mirror image relationship between the enantiomeric pairs / and / in solution. CD spectra are dominated by the metal-centered Λ- or Δ-chirality of non-planar four-coordinated nickel, this latter being in turn dictated by the ligand chirality. Single crystal structure determination for and shows that there are two symmetry-independent molecules (A and B) in each asymmetric unit that give a Z' = 2 structure. Two asymmetric and chiral bidentate N^O-chelate Schiff base ligands coordinate to the nickel atom in a distorted square planar N2O2-coordination sphere. The conformational difference between the symmetry-independent molecules arises from the "up-or-down" folding of the naphthaldiminato ligand with respect to the coordination plane, which creates right- (P) or left-handed (M) helical conformations. Overall, the combination of ligand chirality, chirality at the metal and ligand folding gives rise to discrete metal helicates of preferred helicity in a selective way. Cyclic voltammograms (CV) show an oxidation wave at ca. 1.30 V for the [Ni(L)2]/[Ni(L)2](+) couple, and a reduction wave at ca. -0.35 V for the [Ni(L)2]/[Ni(L)2](-) couple in acetonitrile.

Synthesis, Structural Characterization, and Chiroptical Studies of Bidentate Salen-Type Lanthanide (III) Complexes.

The salen-type ligand prepared with (R,R) diphenylethan-1,2-diamine and salicylaldehyde provides stable and inert complexes KLnL2 upon simple reaction with lanthanide halides or pseudohalides LnX3 (Ln = Tb(3+) -Lu(3+) ; X = Cl(-) or TfO(-) ) of its potassium salt. All the complexes were completely characterized through nuclear magnetic resonance (NMR), electronic circular dichroism (ECD) in the UV and some (Er(3+) , Tm(3+) , Yb(3+) ) also with Near-IR ECD (NIR-ECD) and luminescence (Tb(3+) , Tm(3+) ). Careful analysis of the NMR shifts demonstrated that the complexes are isostructural in solution and afforded an accurate geometry. This was further confirmed by means of Density Functional Theory (DFT) optimization of the Lu(3+) complex, and by comparing the ligand-centered experimental and time-dependent TD-DFT computed UV-ECD spectra. As final validation, we used the NIR-ECD spectrum of the Yb(3+) derivative calculated by means of Richardson's equations. The excellent match between calculated and experimental ECD spectra confirm the quality of the NMR structure.

Optical Activity in the Near-IR Region: The λ=980 nm Multiplet of Chiral Yb3+ Complexes.

We used a very simplified electrostatic model based on charge and polarizability of atoms and groups on an organic ligand around a lanthanide ion to predict the near-infrared electronic circular dichroism (NIR ECD) spectra of Yb3+ (a monoelectronic ion). We tuned our method by using two widely different complexes. The first was the heterobimetallic species CsYb(hfbc)4 [hfbc=(-)-3-heptafluorobutyrylcamphorate], in which the ligand is a diketonate and, as such, is endowed with a chromophore with strong UV absorption (π-π* ). Its oxygen atoms define a square antiprism, which provides a symmetric coordination polyhedron. The second system was Yb DOTMA [DOTMA=(1R,4R,7R,10R)-α,α',α'',α'''-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid], a chiral Yb analogue of Gd DOTA (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), in which the ligand lacks relevant electronic transitions and provides a dissymmetric cage. The relative weights of dynamic (ligand polarization) and static contributions to Yb NIR ECD were evaluated, and the spectra appear to have been well predicted by theory through the introduction of a heuristic weight factor. To validate the approach and to confirm the value of the weight factor, we applied it to two other compounds, namely, Na3 Yb(BINOLate)3 and Yb(BINOLAM)3 [BINOLate=2,2'-dihydroxy-1,1'-binaphthyl; BINOLAM=3,3'-bis(diethylaminomethyl)-1-1'-bi-2-naphthol].

New potent antibacterials against Gram-positive multiresistant pathogens: effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles.

The effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles have been studied to design new potent antibacterials against Gram-positive multidrug-resistant pathogens. The adopted strategy involved a molecular modelling approach, the synthesis and biological evaluation of new designed compounds, enantiomers separation and absolute configuration assignment. Experimental determination of the antibacterial activity of the designed (S)-1-((3-(4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea and (S)-1-((3-(3-fluoro-4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea against multidrug resistant linezolid bacterial strains was higher than that of linezolid.

Induced chirality-at-metal and diastereoselectivity at Δ/Λ-configured distorted square-planar copper complexes by enantiopure Schiff base ligands: combined circular dichroism, DFT and X-ray structural studies.

Bidentate enantiopure Schiff base ligands, (R or S)-N-1-(Ar)ethyl-2-oxo-1-naphthaldiminato-κ(2)N,O, diastereoselectively yield Δ/Λ-chiral four-coordinated, non-planar Cu(N^O)2 complexes [Ar = C6H5 R/S-L1, m-C6H4OMe R-L2, p-C6H4OMe R/S-L3, and p-C6H4Br R/S-L4]. Two N,O-chelate ligands coordinate to the copper(II) atom in distorted square-planar mode, and induce metal-centered Δ/Λ-chirality at the copper atom in the C2-symmetric complexes. In the solid state, the R-L1 (or R-L4) ligand chirality diastereoselectively induces a Λ-Cu configuration in Λ-Cu-R-L1 (or Λ-Cu-R-L4), the S-L1 ligand a Δ-Cu configuration in Δ-Cu-S-L1, forming enantiopure crystals upon crystallization. Conversely, the R-L2 ligand combines both Λ/Δ-Cu-R-L2 as a diastereomeric pair in the crystals. In solution, electronic circular dichroism (CD) spectra show full or partial diastereoselectivity towards Λ-Cu for R ligands and towards Δ-Cu for S ligands. The electronic CD spectra measured on all complexes obtained from R ligands (or S ligands), e.g. Cu-R-L1, Cu-R-L2, Cu-R-L3, and Cu-R-L4 (or Cu-S-L1, Cu-S-L3, and Cu-S-L4), show consistent spectral features. TDDFT calculations of the electronic CD spectra for the diastereomers Λ-Cu-R-L1 and Δ-Cu-R-L1 suggest that the CD spectra are largely dominated by the configuration at the metal center (Λ vs. Δ). The experimental CD spectrum of Cu-R-L1 agrees well with the one calculated for the Λ-Cu-R-L1 configuration. Cyclic voltammetry of Cu-R-L1 reveals a quasi-reversible redox wave corresponding to one-electron transfer for the [Cu(II)L2](0)/[Cu(I)L2](-1) couple in acetonitrile. DSC analyses for the complexes show an exothermic peak between 377 and 478 K (ΔH = -12 to -43 kJ mol(-1)), corresponding to a phase transformation from distorted square-planar/tetrahedral to regular tetrahedral geometry on heating.

A simple and general method to determine reliable pseudocontact shifts in lanthanide complexes.

Pseudocontact shifts (PCS) contain a wealth of geometric information, which makes paramagnetic NMR one of the best methods for accurate geometric determinations in solution. It is well-known that PCS are intrinsically linked to Fermi contact (FC) shifts, and the separation of the two terms is achieved through linearization methods, which heavily rely on (a) isostructurality (even concerning a labile axial site) and (b) the validity of Bleaney's constants. Recently we proposed a method that circumvents both assumptions in the case of axially symmetric complexes, and presently we generalize it to lower symmetry. Our method is model-free and thus does not rely on any structural hypothesis. Our results compare very well with recently published data obtained through an accurate ab initio approach.