Proton relays

Early conformational studies by HOESY experiments are illustrated by the work of Batta and Kover54 who were able to access oligosaccharide sequencing and conformational distribution around the glycosidic bond in model compounds. These determinations make use of relayed proton-proton-carbon cross-relaxation. 

Relayed proton /-couplings within a coupled spin system. Remote protons may be correlated provided there is a continuous coupling network in between them... 

The inverse-detected 2D NMR experiments that have been discussed to this point have all been discrete, single-purpose experiments, e.g. correlating protons with their directly bound heteronucHde (typically or N). There are another class of inverse-detected 2D NMR experiments that are generally referred to as hyphenated 2D experiments. These are experiments that first establish one type of correlation, followed by an additional experiment segment that then pursues a further spectroscopic task. Predecessors of the inverse-detected variants of these experiments were the HC-RELAY (proton—carbon heteronuclear relayed coherence transfer) experiments pioneered by Bolton [151—155]. Examples of these include, but are by no means hmited to HXQC-COSY and -TOCSY [156—158], -NOESY [159], -ROESY [160], and more recent gradient variants [161] etc., where X = S (single) or M (multiple) quantum variants of the experiments. 

We next study water-assisted (relayed) proton transfer in formamide, comparing with a forced proton transfer within formamide in gas phase (Fig. 7.10), which are also associated with the tautomerization. We start from the enol (imidic acid) form HO-CH=NH and track the transfer process to the keto (amide) form 0=CH-NH2. We first survey the above very basic puzzles with this system, identifying that this is indeed a proton... 

Fig. 7.10 (a) Forced proton transfer of formamide in gas phase, (b) Relayed proton... 

The C-H bond cleavage in Cx-C3 alkanes by binuclear Au(I)-rutin and Au(I)-quercetin aqua complexes has been studied by applying DFT to the mechanism of electrophilic substitution with relay proton transfer fi om the alkane to the O atom of the bioflavonoid ligand via a water molecule. The influence of the medium on the energy proflle of the processes is taken into account. The results of studying the energy characteristics of the interaction of the intermediate Me complex with O2 have been used to construct a catalytic cycle for the oxidation of methane to methanol under mild conditions. ... 

Heteronuclear Relayed Proton Correlated Spectroscopy (HERPECS)... 

Figure 5.79. (A) In heteronuclear relayed proton correlated spectroscopy (HERPECS), the coherence is transferred first from to a heteronuclear spin, X, and is then relayed and detected at the third nucleus, Hg. (B) A schematic representation of INADEQUATE, H,H-COSY, and H,C-COSY, relayed H,C-COSY, H,C-COLOC, and HERPECS experiments.

Figure 5. Schematic representation of three spins, A, B, and C interaeting via direct dipolar contacts (black arrows) and/or spin diffusion (dashed arrows), a) Trace of a 2D NOESY spectrum (right) and a corresponding trace from a 2D ROESY spectrum (left). Spins A and B are close in space, and spin diffusion mediates magnetization transfer between protons A and C, that are not close in space. The 2D ROESY experiment allows unambiguous discrimination between direct and spin diffusion effects, b) Protons A and C are close in space, and in addition magnetization is transferred between the two protons via spin diffusion. The effect is a cancellation of the 2D ROESY signal. A cancellation can also occur if indirect magnetization transfer involves more than one relay proton (proton B in this case). Therefore, a discrimination between spin diffusion and direct dipolar interaction is not possible in this case.

FIGURE 7.2. Two alternative mechanisms for the catalytic reaction of serine proteases. Route a corresponds to the electrostatic catalysis mechanism while route b corresponds to the double proton transfer (or the charge relay mechanism), gs ts and ti denote ground state, transition state and tetrahedral intermediate, respectively. 

Double proton transfer mechanism, see Serine proteases, charge-relay mechanism... 

Figure 7-7. Catalysis by chymotrypsin. The charge-relay system removes a proton from Ser 195, making it a stronger nucleophile. Activated Ser 195 attacks the peptide bond, forming a transient tetrahedral intermediate. Release of the amino terminal peptide is facilitated by donation of a proton to the newly formed amino group by His 57 of the charge-relay system, yielding an acyl-Ser 195 intermediate. His 57 and Asp 102 collaborate to activate a water molecule, which attacks the acyl-Ser 195, forming a second tetrahedral intermediate. The charge-relay system donates a proton to Ser 195, facilitating breakdown of tetrahedral intermediate to release the carboxyl terminal peptide .

Stoner-Ma D, Melief EH, Nappa J et al (2006) Proton relay reaction in green fluorescent protein (GFP) polarization-resolved ultrafast vibrational spectroscopy of isotopically edited GFP. J Phys Chem B 110 22009-22018... 

In 2003, Sprang and Bigler have developed a pulse sequence, HMBC-RELAY, subsequently improved in 2004, that yields two simultaneously detected types of long-range correlation spectra.60,61 One spectrum shows all 7ch connectivities while the other shows exclusively 2/ch connectivities. Their method uses homonuclear 3/hh couplings between the protons of adjacent carbons, as already been exploited for the XCORFE... 

The HMBC-RELAY experiment has merit, but suffers from several deficiencies. First, 2/ch signals for quaternary carbons are missing since the transfer of coherences from carbon to protons is restricted to protonbearing carbons. This is also the drawback of the 2/,3/-HMBC experiment. 

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