State-dependent interactions

Using a single lonWorks instrument to screen four plates per day, we completed the entire campaign in fewer than 10 days. As expected, most compounds had little effect on the amplitude of the K+ current. However, active compounds were identified on most screening plates (Figure 4.6B). Some of the active compounds appeared to display state-dependent interactions with the channel, as evidenced by acceleration of the current inactivation kinetics, suggestive of open-state channel block (Figure 4.6C). 

The state-dependent interactions are critically related to the moleciflar features of the drugs and thus the determination of the molecular features of the compounds that would favor the state dependence of the interactions can fa-... 

The properties of drug binding are often modulated by state-dependent interactions whereby the affinity or access of a drug for its binding site is determined by the state - open, closed or inactivated - of the channel. 

Pharmacokinetic properties Source of Ca " mobilized Class and subclass of Ca " channel State-dependent interactions Pathology of tissue and channel regulation. These origins have been discussed previously [ 7,11 ]. assume further importance with the second-generation 1,... 

We begin by considering the nature of interactions between atoms in a metal and we introduce the concept of a state-dependent interaction, that is, an inter-atomic interaction that depends on the thermodynamic state of the system. Later in the chapter we survey possible theoretical mechanisms underlying the metal-nonmetal (MNM) transition and its relation to the thermodynamic phase behavior of the system. We limit this discussion to a summary of the main physical concepts, defining quantities that will prove useful when considering experimental results in subsequent chapters. Readers interested in the detailed development of the theory will eventually wish to consult the original literature and various reviews more specifically focused on theory. 

The conceptual problems raised by strongly state-dependent interactions are especially evident in connection with the critical point terminating the liquid-vapor phase line (Fig. 2.2a). Consider a continuous... 

It may be helpful at this point to summarize briefly the characteristic differences between fluid metals and semiconductors with respect to the state-dependent interaction. Compared with typical metals, the state-dependence of the interparticle interactions in semiconductors is much more closely associated with specific features of the fluid structure. In the liquid chalcogens, for example, these ttike the form of various molecular species including polymeric chains. In semiconducting liquid alloys, it is the short-range correlation of unlike atoms that is important. Consequently, as will be evident in chapter 5, experimental studies of fluid semiconductors are inevitably focused on the fluid structure, either with direct structural probes or more indirect methods such as magnetic studies. Determination of the arrangement of atoms in metallic liquids is also... 

We have seen that the MNM transition and state-dependent interactions are central features of the phase behavior of fluid metals and semiconductors. The existence of a critical point forces us to deal not only with the discontinuous electronic transition coinciding with the liquid-vapor transition, but also with the continuous transition fl om metal to nonmetal implied by the trajectory shown in Fig. 2.2(a). Let us now consider some microscopic electronic mechanisms that could underlie such continuous transitions. We begin with a description of the metallic limit and the model of nearly-ffee-electrons. 

The relation of the state-dependent interaction in mercury to the iso-choric parameters yy and p, can be appreciated with the help of a modified hard-sphere version of the van der Waals equation of state, Eq. 

Inclusion of selenium in a book on fluid metals is justified by its status as a borderline metal at high temperatures and pressures. Also, as we have discussed in chapter 2, the dramatically different molecular structure of the low-temperature liquid and the vapor means that selenium is an excellent example of a system with strongly state-dependent interactions. Structural evolution of the liquid as it is heated to the region of the critical point must inevitably lead to interesting changes in the physical properties. 

The presence of strong state-dependent interactions in metals does not imply that the critical exponents of thermodynamic properties are different from those of molecular fluids. Early speculation that metals might belong to a different universality class than molecular fluids was mainly based on the assumption that the Hamiltonian of metallic systems consists of a sum of long-range Coulomb interactions (Sec. 2.1). We will see that this idea is clearly ruled out by analysis of the coexistence curves in the critical regions. 

In other words, the reactivity of BENAs depends on the presence of the nitrogen lone pair, which is almost coplanar to the C,C double bond in the transition state for interaction with electrophiles. 

---