F- -H Interactions

The fluorine atom in a C-F bond can only act as a proton acceptor in a hydrogen bond, while the oxygen atom in the C-OH bond can act both as a proton donor and acceptor. The result for oxygen is a cooperative effect - oxygen (as 0-H) can both give and accept hydrogen bonds, as shown in Fig. 9, while fluorine can only accept them. 

An interaction between a C-F bond and a metal ion (C-F---M +) has been observed so far by X-ray diffraction studies only when the metal ion is an alkaU metal ion [40]. The coordination of carbon-bound oxygen and fluorine atoms around the metal ion can be analyzed in terms of the requirement that the siun of the bond valences should be near 1.0 for a monovalent cation [43]. This siun is only achieved if the M°+- -F-C interaction is taken into accoimt as well as those involving oxygen atoms. The fluorine atom contributes to the local neutraUza-tion of the charge of the cation, and is, indeed, a significant member of the first coordination sphere of the metal ion. 

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Based on these values, if the three conformations in Fig. 2.8 contributed equally, the vicinal F—H coupling constant should be 16 Hz. Since the actual value was estimated to be 14 Hz, this would indicate that conformer A (with only gauche 3-bond F—H interactions) must be slightly favored. 

A study of the vibrational spectra and force field of this molecule in dilute solution showed that this preferred conformation could not be transposed to the liquid state because there exist in solution some (F. .. H) hydrogen bonding interactions which, not being affected by dilution, must consequently have an intramolecular character. Such (F. .. H) interactions cannot be understood from the solid-state preferred conformation so that we had to reexamine the conformational analysis of (CH3)2SO BF3. 

Although fluorides play a crucial Role in some Ir-catalyzed reactions [9,41], experimental information regarding relevant Ir-fluoride complexes is scarce. Vaska-type fluoride complexes have been reported but are not well characterized [42], while structurally characterized Ir-fluorides are even rarer [43]. Crabtree and coworkers estimated the hydrogen bridge strength of the F. .. H interaction in complexes 62 and 63 (see below) to be approximately 5-7kcalmol [29]. On the other hand,... 

Weber, T. A., and Stillinger, F. H., Interactions, local order, and atomic rearrangement kinetics in amorphous nickel-phosphorus alloys. Phys. Rev. B 32,5402 (1985). 

The intramolecular cooperative C-F-H interaction was found to affect the rigidity of polysilanes." While 221b showed only negligible, weak Cotton effect, 221a exhibited CD spectra characteristic of a stable helical chain with single-handed screw sense. This effect is attributed to the chain stiffness of 221b induced by the intramolecular weak interaction between the pendent fluorine atoms and the Si backbone. 

Predictive models for drug-polymer miscibility have been introduced, and they are largely derived from solution thermodynamics. Lattice-based solution models, such as the F-H theory, can be used to assess miscibility in drug-polymer blends, for which the F-H interaction parameter can be considered as a measure of miscibility. In addition, solubility parameter models can be used for this purpose. The methods used to estimate interaction parameters include melting point depression and the determination of solubility parameters using group contribution theory. 

The F-H interaction parameter can be estimated from solubility parameters as follows. First, the enthalpy of mixing for a drug-polymer system can be described by Eq. 2.42 ... 

ASD including the use of in silico solubility parameter (5) calculation (Ghebremeskel et al. 2007), Flory-Huggins (F-H) interaction parameter calculation (Marsac et al. 2006b Zhao et al. 2011), drug-polymer thermodynamic phase diagrams prediction (Tian et al. 2013), crystallization inhibition with molecular dynamic calculation (Pajula et al. 2012), etc. However, in spite of their use and popularity, these theoretical methods have limitations and lack predictability, reliability, and thereby have limited utility. 

When the AG j is negative, mixing will occur. According to the Flory-Huggins theory, the Gibbs free energy of mixing is expressed as a function of an F-H interaction parameter,[29] ... 

The value of the F-H interaction parameter,can be estimated on the basis of melting point depression data collected by a suitable thermal analysis method, such as DSC ... 

Although the F-H interaction parameter, x> expresses mainly the enthalpic contributions to miscibility, it is not completely free of entropic components, and varies with temperature, T, and composition, 9 [31] ... 

The presence of inter- and intra-molecular C-F---H contacts is mostly supported by crystallographic data. Often a F---H distance shorter than the sum of the F and H van der Waals radii (-2.65 A) is used as evidence for a C-F---H interaction [129]. A review of the PDB in 2004 using this distance criterion as well as directional constraints found that ""...there is an 18% chance that a generic PDB entry with a co-crystallized fluorine-containing ligand presents a hydrogen-bond occurring al the fluorine and that ""10% of the overall amount of fluorine atoms from the PDB... 

Fig. 31 C-F H interaction in (a) 2 -fluoroflavonol (b) 0-alkyl 9-dehydro-9-trifluoromethyl-9-epiquinidines (c) 8-fluoro-iV,iV-drmethylnaphthalen-l-amine...

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