2-Pyridones 2 molecules

As a model reaction for DNA damage by photodimerization of its thymine component, which finally causes a skin cancer, photodimerization reactions of 2-pyridone derivatives are interesting. Photoirradiation of a 1 2 inclusion complex of 66 a and 66 b with the host 67 gives the corresponding rac-cis-anti dimer 68 a and 68 b, respectively [37, 38], Photoirradiations of 66 c and 66 b in their inclusion complexes with 67 and 69, respectively, gives rac-trans-anti dimer 70 c and meso-cis-syn dimer 71 b, respectively [38, 39]. X-ray analysis of these inclusion complexes showed that 2-pyridone molecules are ordered at adequate positions for the corresponding photodimerization reactions in all cases [37-39]. 

The formation of a hydrogen-bonded dimer between a-pyridone molecules proceeds according to the reaction shown in Fig. P8-1. The kinetics of this reaction has... 

The most accurate calculations of the mono- and dihydrated complexes of 2-pyridone have been performed at the MP2/6-31+G(d,p) level [102]. Aecording to these data the lowest energy monohydrated complex of the 2-pyridone molecule has the same type of the structure as in the case of the simplest prototypic molecules, i.e. the water molecule acts as a proton donor to the carbonyl oxygen and as a proton acceptor to amino group. The ealeulated geometrical parameters (Figure 4) are in excellent correspondence with the experimental data which were obtained from the rotationally resolved S]<- So fluorescence excitation spectrum [103]. They are also verified by the correspondence of the calculated rotational constants to ones measured experimentally. 

Unfortunately, the results of the computational studies of the interaction of 2-pyridone molecule with more than two water molecules are unavailable to us. Also note that according to the combined experimental and theoretical study [104] of the different monohydrated forms of oxo- and hydroxopyridines, the monohydrated hydroxo-form is predominating in the Ar matrix, so more careful investigation of the potential surface topology is needed for the hydrated 2-pyridone complexes. 

Certain molecules that can permit concerted proton transfers are efficient catalysts for reactions at carbonyl centers. An example is the catalytic effect that 2-pyridone has on the aminolysis of esters. Although neither a strong base (pA aH+ = 0.75) nor a strong acid (pJsfa = 11.6), 2-pyridone is an effective catalyst of the reaction of -butylamine with 4-nitrophenyl acetate. The overall rate is more than 500 times greater when 2-pyridone acts... 

Pyridones and other six-membered compounds (functional tautomerism). The pyridone /hydroxypyridine tautomerism (76AHCS1, p. 87), especially 2-pyridone (15a)/2-hydroxypyridine (15b), has received more attention from theoreticians than any other example of tautomerism, probably in part because it is a simple model for biologically important molecules such as thymine, cytosine, and uracil (Scheme 8). 

Second generation COMT inhibitors were developed by three laboratories in the late 1980s. Apart from CGP 28014, nitrocatechol is the key structure of the majority of these molecules (Fig. 3). The current COMT inhibitors can be classified as follows (i) mainly peripherally acting nitrocatechol-type compounds (entacapone, nitecapone, BIA 3-202), (ii) broad-spectrum nitrocatechols having activity both in peripheral tissues and the brain (tolcapone, Ro 41-0960, dinitrocatechol, vinylphenylk-etone), and (iii) atypical compounds, pyridine derivatives (CGP 28014,3-hydroxy-4-pyridone and its derivatives), some of which are not COMT inhibitors in vitro but inhibit catechol O-methylation by some other mechanism. The common features of the most new compounds are excellent potency, low toxicity and activity through oral administration. Their biochemical properties have been fairly well characterized. Most of these compounds have an excellent selectivity in that they do not affect any other enzymes studied [2,3]. 

Mixed O, N donor molecules are truly extensive and structurally diverse, and only a few selected examples will be presented. In line with other 2-substituted pyridine analogs reported in this chapter, it is worthwhile noting the chemistry of 2-pyridone (or 2-hydroxypyridine, Hopy), which can form O-bonded monodentate complexes such as Co(Hopy)4(N03)2, but as the monoanion is an effective chelate ligand, forming Co(opy)2 and Co(bpy)(opy)2 compounds.454 An unusual solid state melt reaction with Co(OAc)2 yields the dodecanuclear cluster Co12 (OH)6(OAc)6(opy )12.455... 

In general, such derivatives are constituted by tetraplatinum complexes having as the main ligand a wide range of bio-compatible molecules. The first, structurally characterized platinum blue complex was the oc-pyridonate [Pt4(NH3)8(C5H4N0)4](N03)5, Figure l.15... 

It has been claimed that cardiotonic activity is retained upon replacement of the pyridone moiety in the amrinone molecule by a 3(2 /)-pyridazinone system (9) [7]. Moreover, the patent literature covers various cardiotonic 6-(pyridyl)-3(2//)-pyridazinones and 4,5-dihydro congeners as exemplified by (10), which have been developed in the United States [8-11], Also 3-amino-... 

Faulkner (1923 1927) reported that mutarotation occurred much more readily in a mixture of pyridine and cresol than in either by itself. Swain and Brown (1952) extended this work and found that a-pyridone, where an acidic and a basic group are incorporated in the same molecule, is an excellent catalyst, 0 05 M concentration giving rise to a reaction 50 times faster in benzene solution than a solution of 0 05 M phenol and 0-05 M pyridine. A 0-001 M solution of a-pyridone was 7000 times more effective than equivalent concentrations of phenol and pyridine. A concerted mechanism was proposed [4]. 

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