Bond formation/activation

Chen YX, Heinen M, Jusys Z, Behm RJ. 2006a. Bridge-bonded formate Active intermediate or spectator species in formic acid oxidation on a Pt film electrode Langmuir 22 10399-10408. 

Amino acids must be activated for translation to occur. Activation ensures that the correct amino acid will be recognized and fiiat there is sufficient energy for peptide bond formation. Activation is the covalent coupling of amino acids to specific adapter molecules. The adapter molecules are called transfer RNA (tRNA). There is atleast one tRNA for each of the 20 naturally occurring amino acids. The tRNA recognize the codons carried by the mRNA and position them to facilitate peptide bond formation. 

Carbon-Carbon Bond Formation Activation of C-H Bonds. 

The kinetics and mechanism for the isomerization of HRu3(/i3-77 -EtSGGMeGMe)(GO)9 to Ru3(/x-SEt)(/.43-77 -GGMeGHMe)(GO)9 have been investigated and the overall process shown to involve G-H elimination, G-S and Ru-Ru bond cleavage, and Ru2(/i-S) bond formation. Activation parameters for the isomerization were determined from the temperature dependence (AH = 127(3) kj mol AS = 56(11) J moP K ) and from the pressure dependence of the rate constant. 

The second application of the CFTI approach described here involves calculations of the free energy differences between conformers of the linear form of the opioid pentapeptide DPDPE in aqueous solution [9, 10]. DPDPE (Tyr-D-Pen-Gly-Phe-D-Pen, where D-Pen is the D isomer of /3,/3-dimethylcysteine) and other opioids are an interesting class of biologically active peptides which exhibit a strong correlation between conformation and affinity and selectivity for different receptors. The cyclic form of DPDPE contains a disulfide bond constraint, and is a highly specific S opioid [llj. Our simulations provide information on the cost of pre-organizing the linear peptide from its stable solution structure to a cyclic-like precursor for disulfide bond formation. Such... 

The second application of the CFTI protocol is the evaluation of the free energy differences between four states of the linear form of the opioid peptide DPDPE in solution. Our primary result is the determination of the free energy differences between the representative stable structures j3c and Pe and the cyclic-like conformer Cyc of linear DPDPE in aqueous solution. These free energy differences, 4.0 kcal/mol between pc and Cyc, and 6.3 kcal/mol between pE and Cyc, reflect the cost of pre-organizing the linear peptide into a conformation conducive for disulfide bond formation. Such a conformational change is a pre-requisite for the chemical reaction of S-S bond formation to proceed. The predicted low population of the cyclic-like structure, which is presumably the biologically active conformer, agrees qualitatively with observed lower potency and different receptor specificity of the linear form relative to the cyclic peptide. 

Compounds containing a double or triple bond, usually activated by additional unsaturation (carbonyl, cyano, nitro, phenyl, etc.) In the ap position, add to the I 4-positions of a conjugated (buta-1 3-diene) system with the formation of a ax-membered ring. The ethylenic or acetylenic compound is known as the dieTwphile and the second reactant as the diene the product is the adduct. The addition is generally termed the Diels-Alder reaction or the diene synthesis. The product in the case of an ethylenic dienophile is a cyctohexene and in that of an acetylenic dienophile is a cyctohexa-1 4-diene. The active unsaturated portion of the dienophile, or that of the diene, or those in both, may be involved in rings the adduct is then polycyclic. 

The activation energy for this step is small and bond formation between a posi tive ion and a negative ion occurs rapidly... 

Many biological processes involve an associa tion between two species in a step prior to some subsequent transformation This asso ciation can take many forms It can be a weak associ ation of the attractive van der Waals type or a stronger interaction such as a hydrogen bond It can be an electrostatic attraction between a positively charged atom of one molecule and a negatively charged atom of another Covalent bond formation between two species of complementary chemical re activity represents an extreme kind of association It often occurs in biological processes in which aide hydes or ketones react with amines via imine inter mediates... 

Chemical Bond Formation (Chemisorption). This is the mechanism that leads to the formation of the strongest bonds between coUectors and mineral surfaces. Chemically adsorbed reagents usuaUy form surface compounds at the active waU sites. The flotation of calcite (CaCO ) and... 

This class of inhibitors usually acts irreversibly by permanently blocking the active site of an enzyme upon covalent bond formation with an amino acid residue. Very tight-binding, noncovalent inhibitors often also act in an irreversible fashion with half-Hves of the enzyme-inhibitor complex on the order of days or weeks. At these limits, distinction between covalent and noncovalent becomes functionally irrelevant. The mode of inactivation of this class of inhibitors can be divided into two phases the inhibitors first bind to the enzyme in a noncovalent fashion, and then undergo subsequent covalent bond formation. 

Thiol esters, which are more reactive to nucleophiles than are the corresponding oxygen esters, have been prepared to activate carboxyl groups for both lactoniza-tion and peptide bond formation. For lactonization S-f-butyl and S-2-pyridyP esters are widely used. Some methods used to prepare thiol esters are shown below. The S-r-butyl ester is included in Reactivity Chart 6. 

Coupling to a mineral surface requires the presence of active hydroxyls on the substrate. The coupling reaction is a multi-step process that proceeds from a state of physisorption through hydrogen bond formation to actual covalent bond formation through condensation of surface hydroxyls with silanols ... 

The concerted nature of proton transfer contributes to its rapid rate. The energy cost of breaking the H—Cl bond is partially offset by the energy released in forming the new bond between the transfened proton and the oxygen of the alcohol. Thus, the activation energy is far- less than it would be for a hypothetical two-step process in which the H—Cl bond breaks first, followed by bond formation between FF and the alcohol. 

In the second major method of peptide synthesis the carboxyl group is activated by converting it to an active ester, usually a p-nitrophenyl ester. Recall from Section 20.12 that esters react with ammonia and amines to give fflnides. p-Nitrophenyl esters are much more reactive than methyl and ethyl esters in these reactions because p-nitrophenoxide is a better (less basic) leaving group than methoxide and ethoxide. Simply allowing the active ester and a C-protected amino acid to stand in a suitable solvent is sufficient to bring about peptide bond formation by nucleophilic acyl substitution. 

Cleavage is achieved with H2O, IPA, or MeOH. These derivatives also serve as active esters in peptide bond formation. ... 

In an investigation by Yamabe et al. [9] of the fine tuning of the [4-1-2] and [2-1-4] cycloaddition reaction of acrolein with butadiene catalyzed by BF3 and AICI3 using a larger basis set and more sophisticated calculations, the different reaction paths were also studied. The activation energy for the uncatalyzed reaction were calculated to be 17.52 and 16.80 kcal mol for the exo and endo transition states, respectively, and is close to the experimental values for s-trans-acrolein. For the BF3-catalyzed reaction the transition-state energies were calculated to be 10.87 and 6.09 kcal mol , for the exo- and endo-reaction paths, respectively [9]. The calculated transition-state structures for this reaction are very asynchronous and similar to those obtained by Houk et al. The endo-reaction path for the BF3-catalyzed reaction indicates that an inverse electron-demand C3-0 bond formation (2.635 A... 

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