Studying chemical reactions is an essential step in the development of new molecules and materials, for all kinds of applications ranging from drug development to battery innovation. The quantum nanoreactor is a computational tool can simulate chemical reactions and identify the most likely products of the reaction. This virtual tool can complement experimental studies and accelerate the exploration of chemical compounds and their reactions.  

In this use case, QuantistryLab's quantum nanoreactor feature was used to investigate the hydrolysis reaction that leads to the activation of cisplatin — the mechanism behind its anticancer properties.  

Molecule of interest: Cisplatin

Cisplatin is the first metal-based anticancer drug to ever be approved. Its discovery was a product of serendipity — Barnett Rosenberg, a biophysics researcher, was studying the effects of magnetic fields on cell division in 1965 when he found that a molecule containing platinum could stop cells from dividing.  

About a decade later, cisplatin was approved as a cancer treatment. Today, it is part of the standard treatment for multiple types of cancer.

Understanding the mechanism of action of cisplatin has been essential to studying and developing chemotherapy drugs based on metal compounds.

The cisplatin molecule contains one platinum atom at its core. The molecule also contains two chlorine atoms that play an essential role in the drug's anticancer properties.

When cisplatin enters a cell, the chlorine atoms are displaced by two water molecules. This process, known as hydrolysis, results in the activation of cisplatin.  

In its activated form, cisplatin can interact with DNA. This interaction makes the DNA chain bend unnaturally, blocking the replication of DNA and therefore blocking cell division. When the cell tries to repair the DNA, cisplatin blocks the process, triggering cell death.

During the hydrolysis of cisplatin, two chlorine atoms (in green) are displaced from the molecule and replaced by water molecules | QuantistryLab

Use case: Cisplatin hydrolysis

With just a few clicks, the QuantistryLab platform allows the user to run metadynamics simulations on a quantum nanoreactor.  

In its basic form, the nanoreactor can be used to explore chemical reactions, identifying likely reaction products and their distribution. Molecules or molecular clusters can be placed in the nanoreactor (and heated, if needed) to trigger chemical reactions, and the reaction products are determined automatically. A machine learning tool then analyzes the complex reaction paths to provide further insights into the products and by-products formed.  

The nanoreactor enables an unguided search for chemical reactions using metadynamics simulations within a spherical cavity or wall potential, confining the reactants. Quantum chemical methods are employed to accelerate the simulations.

To investigate the activation reaction of cisplatin inside the cell, a nanoreactor simulation was used to study the effects of water on the molecule. Doing this is easy with QuantistryLab thanks to its Click&Simulate technology.  

A liquid formulation consisting of cisplatin and water molecules can be prepared in QuantistryLab by simply selecting the compounds from the library and setting their ratio.

Cisplatin in water solution | QuantistryLab

Once the formulation is ready, a simulation workflow can be started with just a click to study the reaction process of cisplatin in solution.  

The results of the nanoreactor simulations revealed the reaction products of cisplatin in water at 20 °C. QuantistryLab successfully found the known transition states and the products of the hydrolysis of cisplatin, where one or two chloride atoms have been replaced by water molecules. As discussed above, this results in the activation of cisplatin, which is a necessary step for the drug to interact with DNA and exert its anticancer effects.  

This use case shows how QuantistryLab can be used to accurately predict the results of an unknown reaction of interest. This same approach can be extended to any number of other applications across multiple areas of interest.  

For instance, quantum nanoreactor simulations can be used to study battery materials and provide insights into the thermal stability of electrolyte formulations.  

Optimizing electrolyte formulations is essential for the development of high-performance batteries. QuantistryLab offers a full range of computational solutions to study the properties of electrolyte formulations, such as thermal stability and viscosity.  

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