The crucial role of metal ions and their ligands, known as chelators, extends across a myriad of biological phenomena, ranging from hemoglobin interacting with iron to chlorophyll binding magnesium. The term “chelate” originating from the Greek word “chela” (the great claw of lobsters [1]), refers to the complex formation between the metal ions and chelators using coordinate bonding.Maintaining defined free metal ion concentrations in experimental procedures is often critical due to the strong regulatory effects on many isolated protein functions and intracellular systems. Divalent metals like calcium, magnesium, and zinc are commonly encountered in biological studies with chelators like EGTA (ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid) also known as Egtazic acid, Adenosine triphosphate (ATP), and Ethylenediaminetetraacetic acid (EDTA), which are frequently employed to buffer these metals. However, direct measurement of free metal ions often presents a challenge due to the limited availability of ion-specific electrodes in many laboratories. Consequently, several software calculators have been developed to estimate the free metal concentrations, such as ‘SPECS’ by Fabiato [2], ‘Chelator’ by Schoenmakers et al. [3], ‘Bound and determined’ by Brooks and Storey [4], ‘Calcium’ by Föhr et al. [5], and ‘MaxChelator’ by Bers et al. [6]. The distinguishing factors among these tools lie in their availability, user interface, and the stability constants utilized, with minor variations in calculation methodologies. These calculations take into account the affinity of chelators to metal ions and protons at specific temperature, ionic strength, and pH. As most stability constants are typically measured at standard conditions (e.g., 20 or 25 °C, 0.1 M ionic strength), apparent stability constants are initially computed for the user-defined experimental conditions, followed by the determination of the distribution of species in the solution. Variations in results among different calculators arise from the use of different protonation and metal-affinity stability constants. While older calculators were programmed in languages less accessible today, MaxChelator developed in JavaScript by Chris Patton in 2010 [6] is readily available through modern browsers. However, the numerous calculators present in the literature do not allow the selection of constants from other sources, while some allow only manual editing of the existing constants. Therefore, development of a software that allows easy selection of the available constants and entry of user-defined constants, alongside improvements in user interface and accessibility, is expected to be a valuable advancement.Metal chelator calculations involve multiple arithmetic operations on numbers with many decimal places, potentially introducing rounding errors, as mentioned for JavaScript-based MaxChelator [6]. JavaScript implicitly converts between strings and floating-point numbers and it relies on the standard double-precision 64-bit binary format, accurate up to 15 digits for integers and 17 for decimals [7, 8]. This inherent limitation in precise representation of the decimals as binary can result in accumulated rounding errors and inaccuracies in computed results. In contrast, Python, a contemporary programming language that achieved high popularity in the scientific community, offers several advantages. Python’s accessibility, extensive scientific libraries and the flexibility in project integration make it an attractive choice [9]. Notably, Python supports a rich variety of numeric data types (integer, float, and complex), and includes a built-in Decimals module, facilitating precise handling of the decimals [10]. User-defined precision in Python yields more reliable results, particularly in scientific computations. Metal-chelator calculators could benefit from such arbitrary-precision arithmetic with the aim to minimize rounding errors.To address these needs and concerns, we developed PyChelator web application (https://amrutelab.github.io/PyChelator/), an open source program, based on the well-established and widely used Maxchelator framework. PyChelator offers enhanced user experience and customization options. The Python code in a Google Colaboratory notebook makes the PyChelator functionalities readily available to the Python-using scientific community for further development.
