SupraFit – An Open Source Qt Based Fitting Application to Determine Stability Constants from Titration Experiments**

Abstract

A novel application to determine stability constants from supramolecular titration experiments is presented. The focus lies on NMR titration and ITC experiments for pure 1 : 1 systems, as well as mixed 2 : 1/1 : 1, 1 : 1/1 : 2 and 2 : 1/1 : 1/1 : 2 systems. SupraFit provides global and local fitting and a global search tool. Statistical methods are implemented and can be applied to analyse the results of nonlinear regression. Monte Carlo simulations, combined with the percentile methods and F‐Test approaches to calculate confidence intervals are supported. The implemented statistical approaches are illustrated and discussed on model functions. All methods are accessible through an intuitive user interface, providing charts for all (kind of) data produced. SupraFit is written in C++, using the Qt Toolkit for the Graphical User Interface (GUI) and the Eigen library for nonlinear regression and is released under the GNU Public License (GPL).

Cycloalkyl Groups as Building Blocks of Artificial Carbohydrate Receptors: Studies with Macrocycles Bearing Flexible Side-Arms

“…The 1 H NMR spectroscopic titrations were performed either with constant receptor concentration and increasing concentration of glucopyranoside(for examples, see Table S1 ) or with constant sugar concentration and variable receptor concentration (inverse titration) in CDCl 3 at 293 K. The programs WinEQNMR [ 71 ] and SupraFit [ 72 ] as well as the mole ratio method were used to analyze the 1 H NMR titration data. The determined binding constants are given in Table 1 .…”

“… a 1:1 Receptor-substrate binding model. b Average K 11 values from multiple 1 H NMR spectroscopic titrations in CDCl 3 (293 K; evaluated on the basis of WinEQNMR [ 71 ] and SupraFit [ 72 ] programs). c Average K 11 values from multiple microcalorimetric titrations in CHCl 3 or CHCl 3 /H 2 O (0.035 M H 2 O) (293 K; evaluated on the basis of NanoAnalyze program).…”

Analysing binding stoichiometries in NMR titration experiments using Monte Carlo simulation and resampling techniques

“…The usage of Monte Carlo simulation (MC) and Bootstrapping (BS) to estimate confidence intervals using the percentile methods as proposed previously (Thordarson, 2011;Lowe, Pfeffer & Thordarson, 2012) has already been presented in an earlier article (Hübler, 2022b). Recently, Kazmierczak, Chew & Vander Griend (2022b) have analysed BS in context of photometric titration experiments, including stock solution errors.…”

“…The individual parameter fitting procedures during Cross Validation are performed as if there were Monte Carlo simulation, including the parallelisation. A benchmark on the MC implementation with respect to the parallelisation was given previously (Hübler, 2022b). However some aspects of the data preparation, that is (a) the generation of the map containing the pseudo-experimental data with left out points and (b) the selection of the pseudo-experimental data, will be discussed in this context.…”

“…Furthermore, the proposed protocol may be independent of NMR titration experiments, but an application to other curve-fitting problems has to be studied in detail, which is out of the scope of this article. All proposed methods are implemented in the recently presented program SupraFit (stable version 2) (Hübler, 2019;Hübler, 2022b) and are accessible through an intuitive user interface. Exploiting the simulation functions in SupraFit, the protocol can be tested for own problems.…”