The Lewis basicity of selected organic bases, modeled by the enthalpies of adduct formation between gaseous BF3 and bases in dichloromethane (DCM) solution, is critically examined. Although ...experimental enthalpies for a large number of molecules have been reported in the literature, it may be desirable to estimate missing or uncertain data for important Lewis bases. We decided to use high-level ab initio procedures, combined with a polarized continuum solvation model, in which the solvated species were the clusters formed by specific hydrogen bonding of DCM with the Lewis base and the Lewis base/BF3 adduct. This mode of interaction with DCM corresponds to a specific solvation model (SSM). The results essentially showed that the enthalpy of BF3 adduct formation in DCM solution was clearly influenced by specific interactions, with DCM acting as hydrogen-bonding donor (HBD) molecule in two ways: base/DCM and adduct/DCM, confirming that specific solvation is an important contribution to experimentally determined Lewis basicity scales. This analysis allowed us to conclude that there are reasons to suspect some gas-phase values to be in error by more than the stated experimental uncertainty. Some experimental values in DCM solution that were uncertain for identified reasons could be complemented by the computed values.
In this review, the principles of gas-phase proton basicity measurements and theoretical calculations are recalled as a reminder of how the basicity PA/GB scale, based on Brønsted–Lowry theory, was ...constructed in the gas-phase (PA—proton affinity and/or GB—gas-phase basicity in the enthalpy and Gibbs energy scale, respectively). The origins of exceptionally strong gas-phase basicity of some organic nitrogen bases containing N-sp3 (amines), N-sp2 (imines, amidines, guanidines, polyguanides, phosphazenes), and N-sp (nitriles) are rationalized. In particular, the role of push–pull nitrogen bases in the development of the gas-phase basicity in the superbasicity region is emphasized. Some reasons for the difficulties in measurements for poly-functional nitrogen bases are highlighted. Various structural phenomena being in relation with gas-phase acid–base equilibria that should be considered in quantum-chemical calculations of PA/GB parameters are discussed. The preparation methods for strong organic push–pull bases containing a N-sp2 site of protonation are briefly reviewed. Finally, recent trends in research on neutral organic superbases, leaning toward catalytic and other remarkable applications, are underlined.
Nitrogen bases containing one or more pushing amino-group(s) directly linked to a pulling cyano, imino, or phosphoimino group, as well as those in which the pushing and pulling moieties are separated ...by a conjugated spacer (CX)n, where X is CH or N, display an exceptionally strong basicity. The n-π conjugation between the pushing and pulling groups in such systems lowers the basicity of the pushing amino-group(s) and increases the basicity of the pulling cyano, imino, or phosphoimino group. In the gas phase, most of the so-called push–pull nitrogen bases exhibit a very high basicity. This paper presents an analysis of the exceptional gas-phase basicity, mostly in terms of experimental data, in relation with structure and conjugation of various subfamilies of push–pull nitrogen bases: nitriles, azoles, azines, amidines, guanidines, vinamidines, biguanides, and phosphazenes. The strong basicity of biomolecules containing a push–pull nitrogen substructure, such as bioamines, amino acids, and peptides containing push–pull side chains, nucleobases, and their nucleosides and nucleotides, is also analyzed. Progress and perspectives of experimental determinations of GBs and PAs of highly basic compounds, termed as “superbases”, are presented and benchmarked on the basis of theoretical calculations on existing or hypothetical molecules.
The Lewis basicity of a series of phosphoryl compounds was examined using DFT and ab initio methods, including solvation effects. The enthalpies of adduct formation with two archetypal Lewis acids, ...antimony pentachloride and boron trifluoride, used to define the donor number DN and the BF3 affinity (BF3A) respectively, were examined. The BF3 adducts allow the use of the high‐accuracy G4 approach, whereas for SbCl5 adducts, three different DFT formalisms, including empirical dispersion corrections, were used because the G4 formalism is not available for third‐row elements. For a comparison with experimental data, solvation effects were taken into account by using the polarizable continuum model. The experimental BF3 affinities were well reproduced by G4 calculations when including PCM solvation. Conversely, comparisons of our calculated values and experimental results reported in the literature show that SbCl5 enthalpies for phosphoramides are in error. In particular the DN for HMPA should be revised.
Erroneous enthalpies? Calculated BF3 and SbCl5 enthalpies of adduct formation, in the gas phase or in solution, are highly correlated. However, though experimental BF3 enthalpies for phosphoryl bases are well reproduced by theory, this is not the case for SbCl5. Experimental SbCl5 enthalpies for phosphoramides appear seriously in error.
This work extends our earlier quantum chemical studies on the gas-phase basicity of very strong N-bases to two series of nitriles containing the methylenecyclopropene and cyclopropenimine scaffolds ...with dissymmetrical substitution by one or two electron-donating substituents such as Me, NR2, N=C (NR2)2, and N=P (NR2)3, the last three being strong donors. For a proper prediction of their gas-phase base properties, all potential isomeric phenomena and reasonable potential protonation sites are considered to avoid possible inconsistencies when evaluating the energetic parameters and associated protonation or deprotonation equilibria B + H+ = BH+. More than 250 new isomeric structures for neutral and protonated forms are analyzed. The stable structures are selected and the favored ones identified. The microscopic (kinetic) gas-phase basicity parameters (PA and GB) corresponding to N sites (cyano and imino in the cyclopropenimine or in the substituents) in each isomer are calculated. The macroscopic (thermodynamic) PAs and GBs, referring to the isomeric mixtures of favored isomers, are also estimated. The total (pushing) substituent effects are analyzed for monosubstituted and disubstituted derivatives containing two identical or two different substituents. Electron delocalization is examined in the two π–π conjugated transmitters, the methylenecyclopropene and cyclopropenimine scaffolds. The aromatic character of the three-membered ring is also discussed.
OBJECTIVE:To assess the usefulness of the “Candida score” (CS) for discriminating between Candida species colonization and invasive candidiasis (IC) in non-neutropenic critically ill patients. A rate ...of IC <5% in patients with CS <3 was the primary end point.
DESIGN:Prospective, cohort, observational study.
SETTING:Thirty-six medical-surgical intensive care units of Spain, Argentina, and France.
PATIENTS:A total of 1,107 non-neutropenic adult intensive care unit patients admitted for at least 7 days between April 2006 and June 2007.
MEASUREMENTS AND MAIN RESULTS:Clinical data, surveillance cultures for fungal growth, and serum levels of (1–3)-beta-d-glucan and anti-Candida antibodies (in a subset of patients) were recorded. The CS was calculated as follows (variables coded as absent = 0, present = 1)total parenteral nutrition ×1, plus surgery ×1, plus multifocal Candida colonization ×1, plus severe sepsis ×2. A CS ≥3 accurately selected patients at high risk for IC. The colonization index was registered if ≥0.5. The rate of IC was 2.3% (95% confidence interval CI 1.06–3.54) among patients with CS <3, with a linear association between increasing values of CS and IC rate (p ≤ 0.001). The area under the receiver operating characteristic curve for CS was 0.774 (95% CI 0.715–0.832) compared with 0.633 (95% CI 0.557–0.709) for CI. (1–3)-Beta-d-glucan was also an independent predictor of IC (odds ratio 1.004, 95% CI 1.0–1.007). The relative risk for developing IC in colonized patients without antifungal treatment was 6.83 (95% CI 3.81–12.45).
CONCLUSIONS:In this cohort of colonized patients staying >7 days, with a CS <3 and not receiving antifungal treatment, the rate of IC was <5%. Therefore, IC is highly improbable if a Candida-colonized non-neutropenic critically ill patient has a CS <3.
The Lewis basicity of a series of phosphoryl compounds was examined using DFT and ab initio methods, including solvation effects. The enthalpies of adduct formation with two archetypal Lewis acids, ...antimony pentachloride and boron trifluoride, used to define the donor number DN and the BF
affinity (BF
A) respectively, were examined. The BF
adducts allow the use of the high-accuracy G4 approach, whereas for SbCl
adducts, three different DFT formalisms, including empirical dispersion corrections, were used because the G4 formalism is not available for third-row elements. For a comparison with experimental data, solvation effects were taken into account by using the polarizable continuum model. The experimental BF
affinities were well reproduced by G4 calculations when including PCM solvation. Conversely, comparisons of our calculated values and experimental results reported in the literature show that SbCl
enthalpies for phosphoramides are in error. In particular the DN for HMPA should be revised.
The gas-phase basicity of nitriles can be enhanced by a push–pull effect. The role of the intercalated scaffold between the pushing group (electron-donor) and the pulling (electron-acceptor) nitrile ...group is crucial in the basicity enhancement, simultaneously having a transmission function and an intrinsic contribution to the basicity. In this study, we examine the methylenecyclopropene and the N-analog, cyclopropenimine, as the smallest cyclic π systems that can be considered for resonance propagation in a push–pull system, as well as their derivatives possessing two strong pushing groups (X) attached symmetrically to the cyclopropene scaffold. For basicity and push–pull effect investigations, we apply theoretical methods (DFT and G2). The effects of geometrical and rotational isomerism on the basicity are explored. We establish that the protonation of the cyano group is always favored. The push–pull effect of strong electron donor X substituents is very similar and the two π-systems appear to be good relays for this effect. The effects of groups in the two cyclopropene series are found to be proportional to the effects in the directly substituted nitrile series X–C≡N. In parallel to the basicity, changes in electron delocalization caused by protonation are also assessed on the basis of aromaticity indices. The calculated proton affinities of the nitrile series reported in this study enrich the gas-phase basicity scale of nitriles to around 1000 kJ mol−1.
The ‘Institut de Chimie de Nice’ (ICN), founded in 2012, celebrates its 10th anniversary in 2022. Today, the ICN is part of the University Côte d'Azur (UCA), one out of nine excellence universities ...in France. ICN is also affiliated to the CNRS. We use the institute's anniversary to reflect on the origins and the successful evolution of research in chemical sciences in Nice, France. We outline research topics and their development towards modern chemistry in Nice that are characterized by innovation and territorial anchoring. At present, four research axes, namely aroma and perfume chemistry, medicinal chemistry, radiochemistry, and material chemistry structure the institute. ICN has created five start‐up companies and includes a technological platform. The ICN is central part of the university and contributes to the advancement in chemical sciences as evidenced by both fundamental research and active contributions to local partnerships.
The Institut de Chimie de Nice (ICN) – chemistry research laboratory of the Université Côte d'Azur and the CNRS (UMR 7272) – is directed by Prof. Dr. Uwe J. Meierhenrich and located in Nice, Côte d'Azur, France, in Parc Valrose. ICN is organized in four research teams: aroma, biomedical, radio‐, and material chemistry. This modern institute celebrates its 10th anniversary in 2022, and this Guest Editorial outlines the history of chemistry in Nice and presents the ICN.
Substituted biguanides are known for their biological effect, and a few of them are used as drugs, the most prominent example being metformin (1,1-dimethylbiguanide, IUPAC name: ...N,N-dimethylimidodicarbonimidic diamide). Because of the presence of hydrogen atoms at the amino groups, biguanides exhibit a multiple tautomerism. This aspect of their structures was examined in detail for unsubstituted biguanide and metformin in the gas phase. At the density functional theory (DFT) level {essentially B3LYP/6-311+G(d,p)}, the most stable structures correspond to the conjugated, push–pull, system (NR2)(NH2)CN–C(NH)NH2 (R = H, CH3), further stabilized by an internal hydrogen bond. The structural and energetic aspects of protonation and lithium cation adduct formation of biguanide and metformin was examined at the same level of theory. The gas-phase protonation energetics reveal that the more stable tautomer is protonated at the terminal imino CNH site, still with an internal hydrogen bond maintaining the structure of the neutral system. The calculated proton affinity and gas-phase basicity of the two molecules reach the domain of superbasicity. By contrast, the lithium cation prefers to bind the less stable, not fully conjugated, tautomer (NR2)C(NH)–NH–C(NH)NH2 of biguanides, in which the two CNH groups are separated by NH. This less stable form of biguanides binds Li+ as a bidentate ligand, in agreement with what was reported in the literature for other metal cations in the solid phase. The quantitative assessment of resonance in biguanide, in metformin and in their protonated forms, using the HOMED and HOMA indices, reveals an increase in electron delocalization upon protonation. On the contrary, the most stable lithium cation adducts are less conjugated than the stable neutral biguanides, because the metal cation is better coordinated by the not-fully conjugated bidentate tautomer.
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