The Guanidinium Ion

The complex formed by thymine with the guanidinium ion (Figs. 6.7, 6.8) and the complex formed by thymine with the aminopyrolidinium ion (Figs. 6.9,6.10) were subjected to ab initio (Hartree-Fock) calculations using the 6-31G find the 3-21G basis sets, in order to... 

The binding energy of the guanidinium ion is found to be higher by 2.9 kcals/mole than the one of the aminopyrrolidium ion. This difference agrees with the fact that netropsin binds better than anthelvencin to DNA but it is too small to account for the experimental difference in binding. 

Apart from complex formation involving metal ions (as discussed in Chapter 4), crown ethers have been shown to associate with a variety of both charged and uncharged guest molecules. Typical guests include ammonium salts, the guanidinium ion, diazonium salts, water, alcohols, amines, molecular halogens, substituted hydrazines, p-toluene sulfonic acid, phenols, thiols and nitriles. 

Infra-red studies [31] and molecular orbital calculations [33,34] have led to the description of the guanidinium ion as a tri-amino carbonium ion with the TT-electron charge distribution shown (IX) Most of the positive charge is located in the vicinity of the central carbon atom. The relevance of this description to the pharmacological properties of guanidinium ions will be discussed later. For typographical convenience, guanidines will be formulated in this review in the unprotonated form. 

The similarity of the guanidinium ion, in which the distance between the carbon and the hydrogen atoms is about 2.1 A, to the hydrated sodium ion [Na(OH2)3] in which the distance between the sodium and the hydrogen atoms is about 2.3A, has been pointed out [33, 36a], and the physiological... 

The above speculation [21] may be extended to include the related quaternary ammonium compounds such as xylocholine (XXXIX). It is probable that the volumes of the guanidinium ion and the trimethylammonium group are similar. The ionic radius of the guanidinium ion (IX) is about 3A the ionic radius of the tetramethylammonium ion has been estimated [300] to be 3-4A, although rather smaller values have also been proposed [301-303]. Crystallographic analyses of muscarine iodide [304], choline chloride [305] and acetylcholine bromide [306] have revealed that the carbon to nitrogen distance is about l-SA, and that a hydrogen bond (C-H-0 distance 2-87-3 07A) exists in the crystals of these compounds. 

Reliable interatomic-distance data are not available for guanidine or the guanidinium ion. 

Figure 12-29 Drawing showing the hydrogen-bonding interactions between the guanidinium ions of arginines 35 and 87 of the micrococcal (staphylococcal) nuclease with the 5 -phosphate of the inhibitor thymidine 3, 5 -diphosphate in the complex of E + I + Ca2+. A possible mechanism is illustrated. A hydroxyl ion bound to Ca2+ carries out an in-line attack on the phosphorus. See Libson et al.S26...

Superelectrophilic activation has also been proposed to be involved, based upon the reactivity of carbocations with molecular hydrogen (a a-donor).16 This chemistry is probably even involved in an enzymatic system that converts CO2 to methane. It was found that A. A -menthyl tetrahy-dromethanopterin (11) undergoes an enzyme-catalyzed reaction with H2 by hydride transfer to the pro-R position and releases a proton to give the reduced product 12 (eq 15). Despite the low nucleophilicity of H2, cations like the tert-butyl cation (13) are sufficiently electrophilic to react with H2 via 2 electron-3 center bond interaction (eq 16). However, due to stabilization (and thus delocalization) by adjacent nitrogen atoms, cations like the guanidinium ion system (14) do not react with H2 (eq 17). 

Another example of a carbon-nitrogen gitonic superelectrophile is the protonated guanidinium ion.49 The guanidinium ion (110) can be proto-nated in FSOsFFSbFj to give the gitonic superelectrophile (111 eq 33),... 

In the proposed mechanism of hydrolysis (16), the carboxylate anion of 13-15 or acetyl Phe is recognized by the guanidinium ion, and the Cu(n) center subsequently hydrolyzes the amide group. Both the electrostatic interaction between carboxylate and guanidinium ions and the Cu(n)-catalyzed amide cleavage would be facilitated by the microenvironment provided by polystyrene. 

The C—N force constant for the tris(dimethylamino) cyclopropenium ion is higher than that for the guanidinium ion 5) as shown below. 

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