Macromolecules, reactivity

FIGURE 5.37 Janus faces of the biotransfbrmation of xenobiotics. On one hand metabolism leads to inactivation and elimination of xenobiotics, but on the other hand many metabolites are reactive and may cause deleterious effects by binding to DNA, proteins, and other macromolecules. 

Toxic reactions occur by several mechanisms activation of metabolism, production of reactive intermediates and subsequent reactions with cell macromolecules, changing receptor responses, or through abnormal defence reactions. Several compounds cause toxicity by mimicking the organism s own hormones or neurotransmitters, or activating the body s endogenous receptors in some non-physiological way. ... 

Mechanisms of Cardiotoxicity Chemical compounds often affect the cardiac conducting system and thereby change cardiac rhythm and force of contraction. These effects are seen as alterations in the heart rate, conduction velocity of impulses within the heart, and contractivity. For example, alterations of pH and changes in ionic balance affect these cardiac functions. In principle, cardiac toxicity can be expressed in three different ways (1) pharmacological actions become amplified in an nonphysiological way (2) reactive metabolites of chemical compounds react covalently with vital macromolecules... 

A monomer is a reactive molecule that has at least one functional group (e.g. -OH, -COOH, -NH2, -C=C-). Monomers may add to themselves as in the case of ethylene or may react with other monomers having different functionalities. A monomer initiated or catalyzed with a specific catalyst polymerizes and forms a macromolecule—a polymer. For example, ethylene polymerized in presence of a coordination catalyst produces a linear homopolymer (linear polyethylene) ... 

The polyelectrolyte covalently functionalized with reactive groups may be viewed as an enzyme-like functional polymer or as a molecular reaction system in the sense that it has both reactive centers and reaction rate-controlling microenvironments bound together on the same macromolecule. 

Macromolecules bearing reactive groups in the repeat units along their chains are capable of multiple interaction with the matrix. As early as 1973, Wilchek prepared Sepharose-based supports chemically modified by chemisorbed polylysine and polyvinylamine [41]. The leakage of dyes covalently bonded to these supports was reduced remarkably as compared to non-modified Sepharose activated by cyanogen bromide. Thus, stable and high capacity affinity adsorbents could be prepared by the introduction of macromolecular spacers between a matrix and a biospecific ligand. 

Adhesion is usually controlled by means of various finishing agents. Mikhalsky noted in [260] that reactions between such agents and thermoplastics are hindered for a number of reasons, one reason being that the chemical structure of the polymer is formed before the treated filler is added. In the majority of cases thermoplastics do not contain reactive groups, if perhaps only at the ends of macromolecules where they enjoy little mobility. The probability of contact between the reactive groups of the agent and the plastic. 

PCSs are systems of chromophores bound into a single macromolecule. Therefore, the study of processes of electronic excitation and energy transfer, as well as the investigation of the ways of deactivation of excited states, should lay a foundation for the understanding of such properties of PCSs as reactivity in photochemical transformations, photosensitizing and photoelectric activity, photoinitiated paramagnetism, etc. 

The observed differences in the reactivity of the nitrile groups in the macromolecules of the copolymers can be explained by an intramolecular nucleophilic interaction of the nitrile groups with the adjacent functional groups applying the same point of view as for adjacent nitrile groups ... 

The inclusion of internal viscosity raises considerably the free-energy storage capacity of a rapidly deforming macromolecule as compared to the idealized Hookean spring model and could play a decisive role in mechanochemical reactivity in transient elongational flow. 

Interest in anionic polymerizations arises in part from the reactivity of the living carbanionic sites4 7) Access can be provided to polymers with a functional chain end. Such species are difficult to obtain by other methods. Polycondensations yield ro-functional polymers but they provide neither accurate molecular weight control nor low polydispersity. Recently Kennedy51) developed the inifer technique which is based upon selective transfer to fit vinylic polymers obtained cationically with functions at chain end. Also some cationic ring-opening polymerizations52) without spontaneous termination can yield re-functional polymers upon induced deactivation. Anionic polymerization remains however the most versatile and widely used method to synthesize tailor made re-functional macromolecules. 

In the same scheme, moreover, it is evident that, besides phosphazene homopolymers, the substitution of the chlorines with two (or more) different substituents leads to the preparation of substituent phosphazene copolymers [263] containing different homosubstituted and heterosubstituted monomeric units. Moreover, the cationic polymerization of phosphoranimines [215-217] produces polymers with hving reactive ends (vide supra) from which the preparation of chain phosphazene copolymers (block copolymers) [220,223,225, 229,232-235,239, 240] formed by different polymeric backbones linked together in a unique macromolecule could be obtained. 

Molecular structural changes in polyphosphazenes are achieved mainly by macromolecular substitution reactions rather than by variations in monomer types or monomer ratios (1-4). The method makes use of a reactive macromolecular intermediate, poly(dichlorophosphazene) structure (3), that allows the facile replacement of chloro side groups by reactions of this macromolecule with a wide range of chemical reagents. The overall pathway is summarized in Scheme I. 

The first is cell injury (cytotoxicity), which can be severe enough to result in cell death. There are many mechanisms by which xenobiotics injure cells. The one considered here is covalent binding to cell macromol-ecules of reactive species of xenobiotics produced by metabolism. These macromolecular targets include DNA, RNA, and protein. If the macromolecule to which the reactive xenobiotic binds is essential for short-term cell survival, eg, a protein or enzyme involved in some critical cellular function such as oxidative phosphorylation or regulation of the permeability of the plasma membrane, then severe effects on cellular function could become evident quite rapidly. 

To summarize from the perspective of pol Tner formation, the most important role of functional groups in pol TTierization is to provide bonds that are relatively easy to break. Because C—H and C—C a bonds are relatively strong and do not break easily, polymerization requires monomers that contain reactive functional groups. To form polymers, bonds in these groups must break, and new bonds that link monomers into macromolecules must form. 

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