Dynamic deconvolution

As proof of principle, Lehn and coworkers individually synthesized all acyl hydrazone combinations from the 13 DCL building blocks and measured their inhibition of acetylthiocholine hydrolysis by ACE in a standard assay. They then established a dynamic deconvolution approach whereby the pre-equilibrated DCL containing all members is prepared, frozen, and assayed. Thirteen sublibraries were then prepared containing all components minus one hydrazide or aldehyde component, and assayed. Active components in the DCL were quickly identified by an increase in ACE activity, observed in sublibraries missing either hydrazide 7 or dialdehyde i, pointing to the bis-acyl hydrazone 7-i-7 as the most likely active constituent. This was in line with the individual assay data recorded earlier resynthesis of this compound characterized it as a low nanomolar inhibitor of the enzyme. 

Bunyapaiboonsri, T. Ramstrom, O. Lohmann, S. Lehn, J.-M. Peng, L. Goeldner, M. Dynamic deconvolution of a pre-equilibrated dynamic combinatorial library of acetylcholinesterase inhibitors. Chembiochem 2001, 2, 438-444. 

Figure 6.2 The pre-equilibrated approach and consecutive dynamic deconvolution.

Pre-Equilibrated and Iterated DCLs-Dynamic Deconvolution and Panning... 

Of the acyl hydrazones formed in this case, active lead compounds containing two terminal cationic heterocyclic recognition groups separated by a spacer of appropriate structure could be rapidly identified using a dynamic deconvolution procedure. 

Wintermark M, Fischbein NJ, Smith WS, Ko NU, Quist M, Dillon WP. Accuracy of dynamic perfusion CT with deconvolution in detecting acute hemispheric stroke. Am J Neuroradiol 2005 26 765104-765112. 

Kinetics of chemical reactions at liquid interfaces has often proven difficult to study because they include processes that occur on a variety of time scales [1]. The reactions depend on diffusion of reactants to the interface prior to reaction and diffusion of products away from the interface after the reaction. As a result, relatively little information about the interface dependent kinetic step can be gleaned because this step is usually faster than diffusion. This often leads to diffusion controlled interfacial rates. While often not the rate-determining step in interfacial chemical reactions, the dynamics at the interface still play an important and interesting role in interfacial chemical processes. Chemists interested in interfacial kinetics have devised a variety of complex reaction vessels to eliminate diffusion effects systematically and access the interfacial kinetics. However, deconvolution of two slow bulk diffusion processes to access the desired the fast interfacial kinetics, especially ultrafast processes, is generally not an effective way to measure the fast interfacial dynamics. Thus, methodology to probe the interface specifically has been developed. 

In order to extract the contributions and dynamics of the ketyl radical and fluoranil anion from the TR spectra obtained with the 416 nm probe wavelength, a deconvolution of the Raman bands were done using a fitting procedure employing a Lorentzian lineshape for the Raman bands of the two intermediates. Figure 3.20 shows a comparison of the best-fit (lines) to the experimental TR spectra (dots) in the left-side spectra and the deconvolution extracted from this best fit for the ketyl radical spectra... 

In an NMR analysis of the effects of /-irradiation induced degradation on a specific polyurethane (PU) elastomer system, Maxwell and co-workers [87] used a combination of both H and 13C NMR techniques, and correlated these with mechanical properties derived from dynamic mechanical analysis (DMA). 1H NMR was used to determine spin-echo decay curves for three samples, which consisted of a control and two samples exposed to different levels of /-irradiation in air. These results were deconvoluted into three T2 components that represented T2 values which could be attributed to an interfacial domain between hard and soft segments of the PU, the PU soft segment, and the sol... 

In microphase-separated systems, ESR spectra may consist of a superposition of two contributions, from nitroxides in both fast and slow-tumbling regimes. Such spectra provide evidence for the presence of two types of domains with different dynamics and transition temperatures. This case was detected for a HAS-derived nitroxide radical in heterophasic polyfacrylonitrile-butadiene-styrene) (ABS) as shown in Figure 5, the fast and slow components in the ESR spectrum measured represent nitroxide radicals located in butadiene-rich (B-rich) and styrene/acrylonitrile-rich (SAN-rich) domains, respectively [40]. These two components were determined by deconvoluting the ESR spectrum of HAS-NO measured at 300 K. 

One would still like to examine the effect of ethidium on the torsional rigidity and dynamics at high binding ratios. One would also like to test the Forster theory for excitation transfer between bound ethidium molecules, since it has been questioned/65- This is possible in principle by deconvoluting the effects of depolarization by excitation transfer on the FPA, as will be shown subsequently. DLS also provides crucial information on this same question. 

Figure 5. (a) Deconvoluted image after correction of the dynamical diffraction effect (b) the same as (a) but showing the atomic arrangement schematically (c) result of deconvolution without dynamical diffraction correction and (d) simulated image based on (b). 

It has been demonstrated that the dynamical scattering effect correction technique is also effective in image deconvolution for restoring the atomic configuration for crystals with interface when the elliptical windows are applied. The technique is essential in improving the quality of deconvoluted images so that the available crystal thickness extends to 10 nm or even bigger for Si. 

Figure 7.5 Deconvoluted, zero charge state mass spectrum demonstrating a hit from a DCL-targeting metallo-[3-lactamase (Bell). The dominant peak corresponds to anrora A kinase linked to extender 23, which is in turn linked to fragment 24 to give 25 (dynamic hit ). Reprinted from Reference 27, with permission from Elsevier, Copyright (2008).

Fig. 13 Deconvolution results for a dynamic weighting test (a) a = 2, (b) a = VRMSEq/RMSE , (c) a = RMSE0/RMSEfc 1, (d) a = 2 RMSE /RMSE x, (e) a = 2RMSE0/RMSEfc 1, all for 100 iterations (f) a = 2RMSE0/RMSEk 1 for 40 iterations.

The first two sections of Chapter 5 give a practical introduction to dynamic models and their numerical solution. In addition to some classical methods, an efficient procedure is presented for solving systems of stiff differential equations frequently encountered in chemistry and biology. Sensitivity analysis of dynamic models and their reduction based on quasy-steady-state approximation are discussed. The second central problem of this chapter is estimating parameters in ordinary differential equations. An efficient short-cut method designed specifically for PC s is presented and applied to parameter estimation, numerical deconvolution and input determination. Application examples concern enzyme kinetics and pharmacokinetic compartmental modelling. 

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