a-new-straightforward-method-for-lipophilicity-logp-measurement-using

A New Straightforward Method for Lipophilicity (log<em>P</em>) Measurement using <sup>19</sup>F NMR Spectroscopy

Fluorination has become an effective tool to optimize physicochemical properties of bioactive compounds. One of the applications of fluorine introduction ...

University of Southampton

A series of neutral ditopic and negatively charged, monotopic host molecules have been evaluated for their ability to bind chloride and dihydrogen phosphate anions, and neutral organophosphorus species dimethyl methylphosphonate (DMMP), pinacolyl methylphosphonate (PMP) and the chemical warfare agent (CWA) pinacolyl methylphosphonofluoridate (GD, soman) in organic solvent via hydrogen bonding. Urea, thiourea and boronic acid groups are shown to bind anions and neutral guests through the formation of hydrogen bonds, with the urea and thiourea groups typically exhibiting higher affinity interactions. The introduction of a negative charge on the host structure is shown to decrease anion affinity, whilst still allowing for high stability host-GD complex formation. Importantly, the affinity of the host for the neutral CWA GD is greater than for anionic guests, thus demonstrating the potential for selectivity reversal based on charge repulsion.

Biasing hydrogen bond donating host systems towards chemical warfare agent recognition.

Organofluorine is a weak hydrogen-bond (HB) acceptor. Bernet et al. have demonstrated its capability to perturb OH···O intramolecular hydrogen bonds (IMHBs), using conformationally rigid carbohydrate scaffolds including levoglucosan derivatives. These investigations are supplemented here by experimental and theoretical studies involving six new levoglucosan derivatives, and complement the findings of Bernet et al. However, it is shown that conformational analysis is instrumental in interpreting the experimental data, due to the occurrence of non-intramolecular hydrogen-bonded populations which, although minor, cannot be neglected and appears surprisingly significant. The DFT conformational analysis, together with the computation of NMR parameters (coupling constants and chemical shifts) and wavefunction analyses (AIM, NBO), provides a full picture. Thus, for all compounds, the most stabilized structures show the OH groups in a conformation allowing IMHB with O5 and O6, when possible. Furthermore, the combined approach points out the occurrence of various IMHBs and the effect of the chemical modulations on their features. Thus, two-center or three-center IMHB interactions are observed in these compounds, depending on the presence or absence of additional HB acceptors, such as methoxy or fluorine.

A Study of Intramolecular Hydrogen Bonding in Levoglucosan Derivatives.

We describe the synthesis and characterisation of open fullerene (1) and its reduced form (2) in which CH and NH are encapsulated, respectively. The  H NMR resonance of endohedral NH is broadened by scalar coupling to the quadrupolar  N nucleus, which relaxes rapidly. This broadening is absent for small satellite peaks, which are attributed to natural abundance  N. The influence of the scalar relaxation mechanism on the linewidth of the  H ammonia resonance is probed by variable temperature NMR. A rotational correlation time of τ =1.5 ps. is determined for endohedral NH , and of τ =57±5 ps. for the open fullerene, indicating free rotation of the encapsulated molecule. IR spectroscopy of NH @2 at 5 K identifies three vibrations of NH (ν , ν and ν ) redshifted in comparison with free NH , and temperature dependence of the IR peak intensity indicates the presence of a large number of excited translational/ rotational states. Variable temperature  H NMR spectra indicate that endohedral CH is also able to rotate freely at 223 K, on the NMR timescale. Inelastic neutron scattering (INS) spectra of CH @1 show both rotational and translational modes of CH . Energy of the first excited rotational state (J=1) of CH @1 is significantly lower than that of free CH .

Neil J. Wells

Chemistry

University of Southampton

A New Straightforward Method for Lipophilicity (logP) Measurement using ¹⁹F NMR Spectroscopy

Neil J. Wells

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Chemistry

University of Southampton

A New Straightforward Method for Lipophilicity (logP) Measurement using 19F NMR Spectroscopy

Chemistry

A New Straightforward Method for Lipophilicity (logP) Measurement using ¹⁹F NMR Spectroscopy