Ligands residence time

Composite Cations Mean Ligand Residence Times J0.5 In Ps Determined By QMCF MD Simulations ( Hg +.lsT Shell, Other Ions At Oxygen Sites)... 

Long, that is, with respect to the ligand residence time. 

Fig. 14.12 Left Intermolecular cross-relaxation rate at 600 MHz as a function of the water residence time (with permission from Ref. [39]) Right waterLOGSY experiment recorded on a ten-compound mixture with CDK2 (bottom) and reference ID spectrum (top). Spectra were collected at 19°C and 600 MHz the concentration of CDK2 was approx. 10 jj,M. The asterisks indicate signals due to a ligand binding to CDK2 (with permission from Ref. [35]).

Considerable attention has been paid to this transformation (which is sometimes referred to as hydration ) in the past 15 years. 2. early example of the effect was the marked acceleration of the base hydrolysis of 2-cyanophenanthroline by Ni +, Cu + and Zn " " ions. The second-order rate constant is lO -fold higher for the Ni complex than for the free ligand, residing mainly in a more positive AS An external OH attack on the chelate was favored but an internal attack by Ni(II) coordinated OH cannot be ruled out. Nickel-ion catalysis of the hydrolysis of the phenanthroline-2-amide product is much less effective, being only about 4 x 10 times the rate for spontaneous hydrolysis. ... 

The idea of drug-target residence time places less emphasis on the strength of receptor-ligand interaction and more emphasis on the duration of receptor-ligand interaction. The duration of interaction is defined as the residence time (t) of the ligand, which is equal to the inverse of koff (Equation 5.23). A closely related variable is dissociative half-life (/, 2), also defined by koll (Equation 5.24).31... 

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