Amino three-center bonds

Three-center bonding in the carbohydrates and the amino acids is therefore a result of excess acceptors over donors, or of proton deficiency. Hence the analogy with the three-center electron bond from electron deficiency in the boron hydrides [76]. 

Three-center bonds can be symmetrical with r3 r2, 0 02 and asymmetrical, in which rt and r2 differ by as much as 1.0 A, 0t is close to 180° and 02 is close to 90°. Examples of these have been well established by the neutron diffraction studies of the amino acids [60, 74] and the pyranose sugars [58]. A case where the decision between two- and three-centered bonding is difficult is illustrated from the neutron analysis of erythritol [77], shown in Fig. 2.3. Although one bond is much longer than the other, both are primarily electrostatic. It is difficult to refer to one as a hydrogen bond and the other as an electrostatic attraction. In this monograph, we call these the major and minor component of a three-center bond. 

The amino acid neutron diffraction data given in Ihble 7.15 is very limited. In part, this is due to the high proportion of three-center bonds in these crystal structures. The data based on the nucleoside and nucleotide X-ray crystal structures shown in Thbles 7.16 and 7.17 provide better statistics over a wider variety of donor-acceptor combinations. The data in Thble 7.15 indicate that the -N(H2)H group is a slightly stronger donor than the /NH. This is not shown in Thble 7.16, where there are only one and ten structures for comparison in two of the categories. Comparing the data from all three tables,... 

Table 8.6. Geometry of three-center bonds In the amino acid crystal structures from neutron diffraction data...

The three-center bonds represent — 70% of the total number of hydrogen bonds in the crystal structures surveyed (Thble 2.3). This is a significantly higher proportion than in the other biological molecules, and was attributed to proton deficiency, which occurs because the amino acids form zwitterionic crystal structures where the predominant hydrogen bonding is between the -NH3 and the... 

In the amino acids, the chelated three-center bonds have the - NH3 group as donor, and they are almost invariably unsymmetrical. The primary and strong interaction is to one of the carboxylate (or sulfate) oxygen atoms, the secondary (and weaker) interaction to the other oxygen atom resulting from stereochemical constraints imposed by packing of the molecules in the crystal lattice. 

Intramolecular hydrogen bonds in the amino acid crystal structures occur as the minor components of three-center bonds in the configuration... 

In 5-aminouridine [AMURID], the weak three-center bond from 0(3 )H includes an intramolecular component ( ) to 0(20 and a rare example of an NH2 acceptor (Fig. 17.19). This group, however, is not conjugated as, for example, the amino group in adenine, guanine, and cytosine, but only in conjugation with the C(5)=C(6) double bond. We assume that it is still pyramidal with the lone electron pair located on the N atom, and therefore serves as hydrogen-bond acceptor. 

The crystal structure of 0(3 )-methyl-l-fi-D-arabinofuranosyl cytosine [MARAFC] (Fig. 17.39) contains a very compact trimer involving a chelated three-center bond formed by 0(5 )-H as donor and cytosine N(3),0(2) as acceptors, with two external bonds, from the 0(2 )-H and the amino group. 

In the crystal structure of guanosine 5 -phosphate 3H20 [GUANPH01] (Fig. 17.56) the free acid of the nucleotide is in the zwitterion form with N(7) pro-tonated. There is a four-membered cycle formed by two water molecules and two phosphate groups which is part of an infinite, homodromic chain. The N(l)-H and amino N(2)-H form a chelated bifurcated hydrogen bond with a phosphate oxygen, and N(2)-H is further involved in a three-center bond with another phosphate oxygen atom. 

Proteins contain, on average, more acceptor than donor sites [596]. Similar proton deficiency in the amino acid zwitterion crystal structures results in the formation of three-center hydrogen bonds rather than in unsatisfied acceptor sites [74] (Part I A, Chap. 2.6). There is less flexibility in the orientation of hydrogen-bond donor and acceptor groups in proteins which would lead to a relatively larger number of unsatisfied acceptor sites. Some of the more unsymmetrical three-center bonds which might have been missed in the survey [596] because of the 3.5 A X - A cut-off limit will also contribute to reduce the number of unsatisfied acceptors in side-chains. 

Internal water molecules tend to form clusters. In general, internal water molecules in protein structures are not found isolated but are assembled in clusters. Their hydrogen-bonding scheme could be derived in actinidin (Fig. 19.13), in lysozyme, and in penicillopepsin, based oh the assumption that water molecules act as double donors and acceptors. In some of the protein structures, which have been analyzed in greater detail, an internal water is associated with three acceptor sites indicating three-center bonding as observed in the amino acid zwitterion crystal structures (see Part IB, Chap. 8). 

An analysis of the water molecule configurations in hydrates of the amino adds, peptides, carbohydrates, purines, pyrimidines, nucleosides and nucleotides is presented in Ihble 22.1. The key to the 12 different observed configurations is given in Ihble 22.2. The water molecules, which are involved only in two-center bonds constitute 63% of the total number of bonds, the others are donors or acceptors of three-center bonds. Similar proportions are observed in all three different classes of molecules. Thq only possibly significant difference is a trend toward more three-coordinated pyramidal configurations with the nucleosides and nucleotides. 

Figure 10.3-40. The rating for the disconnection strategy carbon-heteroatom bonds is illustrated, Please focus on the nitrogen atom of the tertiary amino group. It is surrounded by three strategic bonds with different values. The low value of 9 for one ofthese bonds arises because this bond leads to a chiral center. Since its formation requires a stereospecific reaction the strategic weight of this bond has been devalued. In contrast to that, the value of the bond connecting the exocyclic rest has been increased to 85, which may be compared with its basic value as an amine bond.

Due to proton deficiency, crystal structures of amino acids display a much higher proportion of three-center hydrogen bonds. Their geometries, given in Th-bles 8.6 and 8.7, are based on neutron diffraction data, of which a relatively large number is available for this class of biological molecules. 

The three-center hydrogen bonds observed in the crystal structures of the amino acids are described in Thble 8.6. They range from symmetrical to unsymmet-rical, as found for the carbohydrates and nucleic acid constituents, but there is a significantly greater tendency to form more unsymmetrical bonds. A particular feature are the chelated three-center hydrogen bonds discussed below. 

Chelated three-center hydrogen bonds and chelated bifurcated hydrogen bonds involve two acceptors or two donors belonging to the same molecule. They are observed in the crystal structures of the amino acids and their salts (Thble 8.7), and in the crystal structures of the nucleic acid constituents (Thble 8.8) ... 

Fig. 19.9. In a-helices, the -carbon atoms of amino acid side-chains in positions n, (n+3), (n+4) form pockets which can harbor a water molecule hydrogen bonded to the peptide C=0 in position n. The peptide oxygen of residue 79 accepts two hydrogen bonds from the peptide N-H of residues 82, 83 in a bifurcated aN distortion geometry and the peptide N-H of residue 88 donates a three-center hydrogen bond in the aci distortion [596]...

Fig. 20.11. Stereo drawing of d(CGCAAAAAAGCG). The amino N(6)-H groups of the central A-tract form three-center (bifurcated) hydrogen bonds with adenine N(6)-H acting as double donors due to the strong propeller twist of the A-T base pairs. Only bases are shown, sugar-phosphate backbone omitted for clarity [702]...

Jeffrey GA, Mitra J (1984) Three-center (bifurcated) hydrogen bonding in the crystal structures of amino acids. J Am Chem Soc 106 5546-5553... 

There are a number of studies which indicate that certain TICT molecules undergo specific interactions with solvent or quencher molecules. One of the early proposals to explain the dual fluorescence of DM ABN was in fact that of a solute-solvent exciplex (excited complex) [26-28]. The first specific interaction documented as such, however, was that of DMABN (and model compounds) with saturated amines, where a mechanism necessitating a close approach was postulated. This was concluded from the lack of correlation of the quenching reactivity with the ionization potential of the amine quencher. However, a correlation was found between the reactivity pattern and the sterical demands of the saturated amine [140,141]. The complexes formed were non-emissive and were proposed to involve a two-center-three-electron bond between the aromatic and the saturated amino group. 

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