Description:MICROWAVE-ASSISTED SYNTHESIS OF CISPLATIN DERIVATIVES FOR ANTICANCER TREATMENT
Field of the Invention
[0001] The disclosed method pertains to the field of microwave-assisted chemical synthesis for preparing cisplatin derivatives used in anticancer therapeutic applications.
Background
[0002] The background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
[0003] Cisplatin and its analogs are platinum-based chemotherapeutic agents widely used in treating various forms of cancer including ovarian, testicular, and bladder carcinomas. Traditional synthetic approaches for cisplatin derivatives often rely on lengthy reflux-based protocols involving multiple steps of heating, cooling, filtration, and ligand substitution reactions under conventional thermal conditions. These traditional methods are not only time-consuming but also suffer from batch-to-batch inconsistency, poor yield control, and unwanted side reactions due to thermal degradation of ligands. Additionally, the lack of precise thermal control in conventional synthesis environments leads to issues of reproducibility and reduced product purity, which is critical for pharmaceutical-grade compounds. Several attempts have been made to reduce reaction time through sonochemical and photochemical means; however, these processes frequently require complex instrumentation and fail to deliver consistent reaction homogeneity. Furthermore, the thermodynamic control inherent to conventional methods often limits the formation of kinetically favorable cis isomers, which are biologically more active. The growing demand for rapid, reproducible, and scalable synthesis protocols for cisplatin derivatives has highlighted the necessity for alternative heating techniques that enable uniform energy distribution, selective ligand coordination, and enhanced reaction kinetics. Microwave-assisted synthesis has emerged as a promising alternative due to its ability to rapidly and uniformly heat polar solvents and reactants without thermal gradients, leading to improved reaction rates and enhanced product purity.
[0004] All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.
Summary
[0005] Various objects, features, and advantages of the disclosed subject matter can be more fully appreciated with reference to the following detailed description of the disclosed subject matter when considered in connection with the following drawings, in which like reference numerals identify like elements.
[0006] The disclosed method pertains to the field of microwave-assisted chemical synthesis for preparing cisplatin derivatives used in anticancer therapeutic applications.
[0007] A microwave-assisted method is provided for synthesizing cisplatin derivatives with enhanced reaction control and product consistency. The method includes the preparation of a precursor solution containing a platinum-based salt, a halide source, and at least one amine-based ligand. The precursor is subjected to microwave irradiation within a sealed reaction vessel at specific frequency and temperature conditions optimized for cis-coordination. The microwave heating enables uniform and rapid thermal energy transfer, reducing reaction times from several hours to a few minutes. Following irradiation, the crude mixture is cooled and subjected to a solvent-assisted precipitation step using a polar/non-polar binary solvent system, leading to the isolation of crude cisplatin derivatives. The crude product is then purified by vacuum filtration and recrystallized using temperature-controlled protocols. Optionally, the resulting compounds are characterized using spectroscopy-based techniques for verifying ligand coordination and structural integrity. This approach eliminates the need for multiple reaction steps and allows synthesis in a single vessel, minimizing contamination risk and improving yield. The integration of microwave irradiation and simplified purification steps offers an efficient and scalable method for producing cisplatin-based anticancer agents.
Brief Description of the Drawings
[0008] The features and advantages of the present disclosure would be more clearly understood from the following description taken in conjunction with the accompanying drawings in which:
[0009] FIG. 1 illustrates a system architecture diagram representing the integrated microwave-assisted cisplatin synthesis apparatus, showing the interconnections between precursor preparation, microwave irradiation module, sealed reaction vessel, purification unit, and characterization instruments.
[00010] FIG. 2 depicts a method flow diagram outlining the sequential steps involved in synthesizing cisplatin derivatives, from precursor solution formulation through microwave irradiation, product precipitation, filtration, recrystallization, and structural analysis.
[00011] FIG. 3 provides a data flow diagram showing how reaction control parameters, sensor feedback, and characterization data interact with the microwave reactor and purification subsystems to facilitate real-time process optimization and quality assurance.
Detailed Description
[00012] The following is a detailed description of exemplary embodiments to illustrate the principles of the invention. The embodiments are provided to illustrate aspects of the invention, but the invention is not limited to any embodiment. The scope of the invention encompasses numerous alternatives, modifications and equivalent; it is limited only by the claims.
[00013] In view of the many possible embodiments to which the principles of the present discussion may be applied, it should be recognized that the embodiments described herein with respect to the drawing figures are meant to be illustrative only and should not be taken as limiting the scope of the claims. Therefore, the techniques as described herein contemplate all such embodiments as may come within the scope of the following claims and equivalents thereof.
[00014] The detailed description is described with reference to the accompanying figures. In the figures, the left-most digit(s) of a reference number identifies the figure in which the reference number first appears. The use of the same reference numbers in different instances in the description and the figures may indicate similar or identical items.
[00015] Pursuant to the "Detailed Description" section herein, whenever an element is explicitly associated with a specific numeral for the first time, such association shall be deemed consistent and applicable throughout the entirety of the "Detailed Description" section, unless otherwise expressly stated or contradicted by the context.
[00016] The disclosed method pertains to the field of microwave-assisted chemical synthesis for preparing cisplatin derivatives used in anticancer therapeutic applications.
[00017] Pursuant to the "Detailed Description" section herein, whenever an element is explicitly associated with a specific numeral for the first time, such association shall be deemed consistent and applicable throughout the entirety of the "Detailed Description" section, unless otherwise expressly stated or contradicted by the context.
[00018] FIG. 1 illustrates a system-level representation of the apparatus utilized for microwave-assisted synthesis of cisplatin derivatives. The architecture begins with a precursor preparation module configured to receive platinum salt, amine-based ligand, and halide source inputs. These reactants are solubilized using a solvent dispensing system and transferred into a sealed reaction vessel situated within the microwave irradiation module. The microwave irradiation module is equipped with frequency control circuitry, thermal monitoring sensors, and a pressurization assembly to maintain specified operational parameters throughout the irradiation cycle. Upon completion of microwave activation, the reaction mixture is routed to a purification unit comprising a precipitation chamber, vacuum filtration assembly, and a temperature-controlled recrystallization module. Downstream from this purification system is a characterization module containing spectroscopic instruments including infrared, UV-Vis, and nuclear magnetic resonance analyzers. The system also includes a control interface enabling coordinated operation of all units with feedback loops originating from embedded sensors that measure internal temperature, pressure, and pH values. This architecture facilitates closed-loop operation, minimizing manual intervention, reducing contamination, and ensuring batch-to-batch consistency during synthesis. The disclosed invention involves a microwave-assisted method for synthesizing cisplatin derivatives used in anticancer treatments. A precursor solution is initially formulated by combining a platinum-based salt such as potassium tetrachloroplatinate(II), sodium tetrachloroplatinate(II), or chloroplatinic acid with a selected amine ligand that facilitates nitrogen coordination. Suitable amine ligands include ethylenediamine, methylamine, and 1,2-diaminocyclohexane. A halide source such as sodium chloride or potassium chloride is introduced into the solution to enable halide ligand exchange and support the formation of neutral platinum complexes. The precursor solution is maintained in a polar solvent such as deionized water, ethanol, or mixtures thereof, promoting uniform microwave absorption. The resulting homogeneous mixture is then transferred into a microwave-compatible sealed reaction vessel capable of withstanding internal pressures and temperatures generated during irradiation.
[00019] The microwave reactor is calibrated to operate at a frequency ranging between 2.4 GHz and 2.5 GHz, delivering thermal energy directly to the dipolar molecules within the solution. Reaction temperatures are monitored and controlled within the range of 60°C to 140°C to avoid ligand decomposition and maintain kinetic favorability for cis-complex formation. The reaction duration ranges between 2 and 10 minutes, depending on the desired conversion efficiency. After microwave exposure, the vessel is allowed to cool to room temperature under inert conditions to prevent oxidation of sensitive coordination complexes.
[00020] The resulting reaction mixture contains crude cisplatin derivatives that are subsequently subjected to a purification phase. A binary solvent system, typically comprising ethanol and water in a 3:1 volumetric ratio, is introduced to induce solvent-assisted precipitation. This precipitation step exploits differential solubility properties of the target cisplatin derivatives, promoting selective crystallization. Vacuum filtration is used to isolate the solid product from the reaction mixture, ensuring the removal of unreacted precursors and soluble by-products. The crude product is then recrystallized by dissolving in an aqueous ethanol mixture followed by gradual cooling over an ice bath. This controlled recrystallization step facilitates the formation of highly uniform crystals with minimal internal stress.
[00021] Spectroscopic characterization of the purified compound is performed using Fourier-transform infrared spectroscopy to verify the presence of metal-nitrogen bonds and halide stretches. UV-Visible spectrophotometry is employed to assess the optical absorption profile, while nuclear magnetic resonance spectroscopy verifies the geometric arrangement and coordination state of ligands. Optional scanning electron microscopy can be performed to visualize crystal morphology.
[00022] In a first alternative embodiment, the platinum precursor is introduced into a solution containing excess methylamine and sodium chloride, and microwave irradiation is performed at 90°C for five minutes. The reaction favors rapid coordination and high-yield formation of dimethylamine-platinum complexes suitable for enhanced intracellular uptake in cancerous tissues. In a second embodiment, 1,2-diaminocyclohexane is employed as the ligand, and the reaction is carried out in ethanol solvent to facilitate hydrophobic ligand coordination. Microwave irradiation is maintained at 120°C for eight minutes, leading to the formation of sterically hindered cisplatin analogs with higher selectivity toward drug-resistant tumor lines. A third embodiment utilizes a solvent-free reaction mixture in which the platinum salt and ligand are triturated and irradiated in a dry state under controlled humidity, leading to solid-phase complexation without solvent waste.
[00023] Each embodiment benefits from the localized and rapid heating provided by microwave irradiation, which shortens synthesis time, reduces thermal gradients, and prevents excessive decomposition. Furthermore, by maintaining all synthesis steps within a single vessel and reducing reliance on mechanical agitation, the method minimizes exposure to contaminants and promotes repeatable, pharmaceutical-grade product formation. The combination of selective ligand exchange, microwave-driven reaction kinetics, and integrated purification steps enables a continuous, scalable, and reproducible route for producing cisplatin derivatives.
[00024] This methodology may be adapted for use in high-throughput pharmaceutical laboratories, where microwave reactors can be coupled with automated liquid handling systems to synthesize multiple cisplatin analogs in parallel. Similarly, real-time monitoring sensors integrated into the reaction vessel may be programmed to dynamically adjust irradiation power and duration based on feedback signals such as pressure spikes or temperature fluctuations. The resulting process automation capability not only reduces human error but also standardizes synthetic yields and purity benchmarks across diverse reaction batches.
[00025] In scenarios where ligand libraries are screened for cytotoxic efficacy, the method allows swift synthesis of structurally diverse derivatives through minor alterations in amine ligands and halide ratios, all within the same standardized microwave synthesis protocol. This reduces chemical waste and accelerates preclinical screening timelines. The disclosed invention thus represents a significant advancement in the field of platinum-based chemotherapy agents by offering a clean, fast, and consistent approach to synthesizing cisplatin derivatives suitable for anticancer applications.
[00026] FIG. 2 represents a procedural depiction of the method for synthesizing cisplatin derivatives using microwave assistance. The process initiates with the preparation of a homogeneous precursor solution through measured addition of platinum salts, halide ions, and amine ligands. This mixture is transferred into a sealed reaction vessel and subjected to microwave irradiation at a specified frequency and temperature range. As the polar solvent and reagents interact with microwave energy, rapid heating promotes cis-coordination of ligands onto the platinum center. After completion of irradiation, the vessel is cooled, and the reaction mixture is subjected to solvent-induced precipitation using a binary ethanol-water system. The resulting solid is isolated through vacuum filtration, followed by recrystallization in an ice-cooled ethanol medium to improve crystal uniformity. The purified cisplatin derivatives are then analyzed through a suite of characterization steps involving spectral and structural validation. This stepwise method ensures reduced synthesis time, improved product purity, and compatibility with automation workflows.
[00027] FIG. 3 delineates the data flow across various components of the cisplatin synthesis system, focusing on how process parameters and analytical feedback are transmitted and processed. Reaction input parameters such as microwave frequency, irradiation time, and temperature are programmed through a control interface. During irradiation, real-time sensor data including vessel pressure and internal temperature are relayed to a microcontroller-based feedback unit that modulates microwave output to ensure process stability. Once the irradiation completes, the filtration and recrystallization parameters are uploaded and executed based on temperature sensor feedback from the purification subsystem. Characterization data such as bond verification from IR, absorption spectra from UV-Vis, and molecular geometry from NMR are digitized and transmitted to a quality assurance module. This module compares current batch data against reference standards and outputs a synthesis quality score to determine compound acceptability. The closed-loop integration of data acquisition, process modulation, and compound evaluation enhances synthesis reliability and facilitates reproducible production of anticancer agents.
[00028] Further, while operations are depicted in a particular order, this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order, or that all illustrated operations be performed, to achieve desirable results. In certain circumstances, multitasking and parallel processing may be advantageous. Likewise, while several specific implementation details are contained in the above discussions, these should not be construed as limitations on the scope of the subject matter described herein, but rather as descriptions of features that may be specific to particular embodiments. Certain features that are described in this specification in the context of separate embodiments can also be implemented in combination in a single embodiment. Conversely, various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable sub-combination. Moreover, although features may be described above as acting in certain combinations and even initially claimed as such, one or more features from a claimed combination can in some cases be excised from the combination, and the claimed combination may be directed to a sub-combination or variation of a sub-combination.

I/We Claim:
CLAIM 1
A method for synthesizing cisplatin derivatives for anticancer treatment comprising the steps of: preparing a precursor solution containing a platinum salt, at least one selected amine-based ligand, and a halide source; subjecting the precursor solution to microwave irradiation at a frequency ranging between 2.4 GHz and 2.5 GHz for a duration ranging from 2 minutes to 10 minutes at a controlled temperature between 60°C and 140°C to induce coordination bonding; obtaining a crude reaction product comprising cisplatin derivatives; and purifying the cisplatin derivatives using solvent-assisted precipitation followed by vacuum filtration and recrystallization.
CLAIM 2
The method of claim 1, wherein said platinum salt is selected from the group consisting of potassium tetrachloroplatinate(II), sodium tetrachloroplatinate(II), and chloroplatinic acid.
CLAIM 3
The method of claim 1, wherein said amine-based ligand is selected from the group consisting of ethylenediamine, 1,2-diaminocyclohexane, methylamine, and piperidine.
CLAIM 4
The method of claim 1, wherein said halide source comprises chloride ions derived from sodium chloride or potassium chloride to facilitate halide exchange during microwave-assisted reaction.
CLAIM 5
The method of claim 1, wherein said microwave irradiation is performed in a sealed, pressurized microwave reaction vessel with real-time temperature and pressure feedback monitoring to avoid thermal degradation of ligands and platinum complexes.
CLAIM 6
The method of claim 1, wherein said solvent-assisted precipitation employs a binary solvent system comprising water and ethanol in a volumetric ratio of 1:3 for selective crystallization of the cisplatin derivatives.
CLAIM 7
The method of claim 1, further comprising a post-synthesis characterization step wherein said purified cisplatin derivatives are evaluated using spectroscopic techniques selected from the group consisting of infrared spectroscopy, UV-Visible spectroscopy, and nuclear magnetic resonance spectroscopy.
CLAIM 8
The method of claim 1, wherein said recrystallization is performed in an ice-cooled aqueous ethanol solution to induce slow nucleation and enhanced crystal uniformity in the final cisplatin derivative product.
CLAIM 9
The method of claim 1, wherein the molar ratio of platinum salt to amine ligand ranges from 1:2 to 1:4, and the total reaction volume does not exceed 50 milliliters to maintain microwave absorption efficiency.
CLAIM 10
The method of claim 1, wherein the entire synthesis is completed in a single reaction vessel without intermediate transfers, enabling contamination-free operation and reproducible batch synthesis of cisplatin derivatives.

MICROWAVE-ASSISTED SYNTHESIS OF CISPLATIN DERIVATIVES FOR ANTICANCER TREATMENT
Abstract
Disclosed is a method for synthesizing cisplatin derivatives using microwave-assisted heating of a precursor solution comprising platinum salts, halide sources, and amine ligands. The solution is irradiated at controlled frequencies and temperatures in a sealed vessel to facilitate cis-coordination of ligands, followed by precipitation, filtration, and recrystallization. The method enables rapid, reproducible, and contamination-free synthesis with enhanced yield and structural purity, suitable for pharmaceutical anticancer applications. , Claims:I/We Claim:
CLAIM 1
A method for synthesizing cisplatin derivatives for anticancer treatment comprising the steps of: preparing a precursor solution containing a platinum salt, at least one selected amine-based ligand, and a halide source; subjecting the precursor solution to microwave irradiation at a frequency ranging between 2.4 GHz and 2.5 GHz for a duration ranging from 2 minutes to 10 minutes at a controlled temperature between 60°C and 140°C to induce coordination bonding; obtaining a crude reaction product comprising cisplatin derivatives; and purifying the cisplatin derivatives using solvent-assisted precipitation followed by vacuum filtration and recrystallization.
CLAIM 2
The method of claim 1, wherein said platinum salt is selected from the group consisting of potassium tetrachloroplatinate(II), sodium tetrachloroplatinate(II), and chloroplatinic acid.
CLAIM 3
The method of claim 1, wherein said amine-based ligand is selected from the group consisting of ethylenediamine, 1,2-diaminocyclohexane, methylamine, and piperidine.
CLAIM 4
The method of claim 1, wherein said halide source comprises chloride ions derived from sodium chloride or potassium chloride to facilitate halide exchange during microwave-assisted reaction.
CLAIM 5
The method of claim 1, wherein said microwave irradiation is performed in a sealed, pressurized microwave reaction vessel with real-time temperature and pressure feedback monitoring to avoid thermal degradation of ligands and platinum complexes.
CLAIM 6
The method of claim 1, wherein said solvent-assisted precipitation employs a binary solvent system comprising water and ethanol in a volumetric ratio of 1:3 for selective crystallization of the cisplatin derivatives.
CLAIM 7
The method of claim 1, further comprising a post-synthesis characterization step wherein said purified cisplatin derivatives are evaluated using spectroscopic techniques selected from the group consisting of infrared spectroscopy, UV-Visible spectroscopy, and nuclear magnetic resonance spectroscopy.
CLAIM 8
The method of claim 1, wherein said recrystallization is performed in an ice-cooled aqueous ethanol solution to induce slow nucleation and enhanced crystal uniformity in the final cisplatin derivative product.
CLAIM 9
The method of claim 1, wherein the molar ratio of platinum salt to amine ligand ranges from 1:2 to 1:4, and the total reaction volume does not exceed 50 milliliters to maintain microwave absorption efficiency.
CLAIM 10
The method of claim 1, wherein the entire synthesis is completed in a single reaction vessel without intermediate transfers, enabling contamination-free operation and reproducible batch synthesis of cisplatin derivatives.