Dipole Moment of A-agents series via Molecular Dynamics Simulations
MICHAIL CHALARIS
Department of Chemistry
International Hellenic University Kavala, GREECE
ANTONIOS KOUFOU
Department of Chemistry
International Hellenic University
Kavala, GREECE
KALLIOPI KRAVARI
Department of Production Engineering and Management
International Hellenic University
Thessaloniki, GREECE
Abstract: The study focused on employing Molecular Dynamics Simulations to determine the dipole moment of Novichok A-agents, which are
notorious as Chemical Warfare agents. These simulations were conducted at the level of isolated molecules, allowing for a focused analysis of
the dipole moment's behavior within the agents. Molecular Dynamics Simulations were chosen as the primary tool for estimating the dipole
moment due to their unique advantages. By simulating the behavior of molecules in a virtual environment, MDS provides a quick and efficient
means of estimating crucial properties. This is particularly significant for substances like Novichok A-agents, which are associated with high
toxicity and extreme sensitivity, making traditional experimental methods challenging. The simulations were executed on isolated molecules, an
approach that simplifies the analysis and enables a more direct examination of the dipole moment's characteristics. This focused perspective
contributes to the accuracy of the results and offers insights into the agents' charge distribution and interactions.
Keywords: A-agents, Molecular Dynamics Simulations, Dipole monent
Received: May 24, 2022. Revised: June 8, 2023. Accepted: July 11, 2023. Published: August 28, 2023.
1. Introduction
Chemical Warfare agents (CWAs) have left a dark mark on
human history, being utilized in major conflicts as well as
sporadic isolated incidents. Despite international efforts such as
the establishment of the Chemical Weapons Convention
(CWC), which aims to prevent the proliferation and use of
chemical weapons, there have been instances of isolated attacks
involving CWAs that continue to occur worldwide. Recent
cases, like the Salisbury (Skripal) poisoning and the Navalny
case, highlight the persistent threat these agents pose.
The Salisbury and Navalny incidents involved the alleged
use of a group of nerve agents known as Novichok agents, often
referred to as the fourth generation of CWAs [1-3]. These agents
are particularly insidious due to their high potency and delayed
onset of symptoms, making detection and treatment challenging.
Novichok agents represent the cutting edge of chemical warfare
technology and have become a significant focus for scientific
efforts to understand, counteract, and mitigate their effects.
The collapse of the Soviet Union raised concerns about the
unaccounted stockpiles of CWAs, which presented a potential
danger as these substances could fall into the wrong hands.
Additionally, the existence of dispersed terrorist groups across
the globe further highlights the ongoing risk associated with
CWAs. Ensuring the strict control and elimination of these
substances has become a paramount priority in combating global
terrorism.
Efforts to prevent the use of CWAs and address the risks
associated with their proliferation involve a multifaceted
approach. This includes:
- International Treaties and Agreements: The Chemical
Weapons Convention is a key instrument in curbing the
production, stockpiling, and use of CWAs. It seeks to
ensure the destruction of existing stockpiles and prevent
their re-emergence.
- Enhanced Detection and Monitoring: Developing
advanced technologies and methods for the rapid
detection and identification of CWAs is crucial to
responding effectively to potential incidents.
- Scientific Research: The scientific community plays a
vital role in understanding the properties and effects of
CWAs. Research informs medical responses, protective
measures, and decontamination protocols.
MOLECULAR SCIENCES AND APPLICATIONS
DOI: 10.37394/232023.2023.3.1
Michail Chalaris, Antonios Koufou, Kalliopi Kravari
E-ISSN: 2732-9992
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- International Cooperation: Collaborative efforts among
countries, organizations, and experts are necessary to
address the global threat posed by CWAs. Information
sharing and joint action can help prevent incidents and
respond to crises effectively.
- Security Measures: Ensuring the secure storage and
management of precursor chemicals used in the
production of CWAs can help prevent unauthorized
access.
- Public Awareness: Raising awareness about the dangers
of CWAs and the importance of international efforts to
counter them can encourage public support for
preventive measures.
In conclusion, while significant progress has been made in
curbing the use and proliferation of CWAs through international
treaties and agreements, challenges persist due to factors such as
the existence of unaccounted stockpiles and the potential for
isolated attacks by terrorist groups. Addressing these challenges
requires ongoing vigilance, scientific research, international
collaboration, and a commitment to preventing the devastating
impact of chemical warfare agents on human lives and the
environment.
The widespread proliferation of the use and manufacturing
of chemical warfare agents (CWAs) has posed significant
challenges for experimental institutes aiming to research these
substances' properties, understand their effects, and develop
effective treatments. The highly sensitive and dangerous nature
of CWAs makes traditional experimental investigation difficult
and risky. This has led researchers to seek alternative methods
to gain insight into the properties and interactions of these
agents. In this context, Molecular Dynamics Simulations (MDS)
emerge as a valuable tool to shed light on the intricate field of
intermolecular interactions involving CWAs.
Molecular Dynamics Simulations involve computer-based
modeling and simulation of molecular systems over time. By
utilizing step-by-step algorithms and solving equations of
motion for numerous interacting molecules within a simulated
environment, MDS offers a unique opportunity to uncover
properties, behaviors, and interactions that would otherwise
remain elusive [4]. This approach has the potential to provide a
deeper understanding of the characteristics of CWAs and the
consequences of their interactions with various systems,
including biological cells.
In previous research endeavors [5,6], the focus was directed
towards utilizing MDS to explore the properties and interactions
of CWAs. This approach aimed to bridge the gap in knowledge
resulting from the challenges associated with experimental
research.
In the present study, the specific focus revolves around the
estimation of dipole moments using MDS. Dipole moment is a
fundamental property of a molecule that arises from the
separation of positive and negative charges within the molecule.
It plays a critical role in determining how molecules interact
with electric fields and other molecules. The calculation of
dipole moments for various A-agents, such as A-230, A-232,
and A-234, is explored in this study. These A-agents are known
to exist in two potential structures each, as indicated in previous
literature [7-9]. This results in a total of six dipole moments that
are calculated and presented in the study.
Calculation of the dipole moment of a molecule is a
fundamental process that provides insight into the molecule's
overall charge distribution and its interaction with electric fields.
This property is particularly significant in understanding how a
molecule might behave in various chemical and physical
environments. The formula used for calculating the dipole
moment (μ) is defined as follows:
𝜇 = ∑𝑞𝑖𝑟𝑖 (1)
𝑖
In this equation, several key components play essential
roles:
- μ (Dipole Moment Vector): The symbol μ represents
the dipole moment vector of the molecule. This
vector points from the molecule's negatively
charged region to its positively charged region,
indicating the direction and magnitude of the
separation of charge within the molecule.
- qi (Individual Atom Charges): The variable qi
represents the individual charges associated with
each atom within the molecule. This charge may be
positive or negative, depending on the atom's
electron configuration and its position within the
molecular structure.
- ri (Distances of Atoms from Center of Mass): The
variable ri signifies the distances of the individual
atoms from the molecule's center of mass. The
center of mass serves as a reference point for
calculating the relative positions of atoms within the
molecule.
The equation's essence lies in the calculation of the
product of individual atom charges (qi) and their respective
distances from the center of mass (ri). Summing up these
products for all atoms within the molecule yields the overall
dipole moment of the molecule.
The unit of measurement for dipole moment is typically
expressed in Debye (D), a unit named after the chemist Peter
Debye. One Debye is equal to 3.34×10-30 C m (coulomb
meter). The Debye unit provides a standardized measure for
dipole moments, facilitating comparisons across different
molecules and systems.
By applying this formula, scientists can quantitatively
evaluate the extent of charge separation within a molecule
and understand its polar nature. This information is crucial
in predicting how the molecule will interact with electric
fields, other molecules, and its environment. In the context
of the study described, the dipole moment calculations are
applied to several A-agents, including A-230, A-232, and A-
MOLECULAR SCIENCES AND APPLICATIONS
DOI: 10.37394/232023.2023.3.1
Michail Chalaris, Antonios Koufou, Kalliopi Kravari
E-ISSN: 2732-9992
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Volume 3, 2023
234, in order to gain insights into their molecular properties
and behaviors.
Importantly, recent findings, particularly those
attributed to Mirzayanov (a former Soviet Union chemist
involved in their CWAs program), have established certain
structures as the closest representation of reality for these
A-agents. These structures have been linked to incidents like
the Salisbury case, which emphasizes their significance [10].
In conclusion, Molecular Dynamics Simulations offer a
promising approach to understanding the properties and
interactions of CWAs, where experimental methods fall
short. The study's focus on dipole moment estimation using
MDS provides valuable insights into the behaviors of specific
A-agents and contributes to the broader goal of
comprehending and addressing the challenges posed by
chemical warfare agents..
2. Methodology
In this research, a specific methodology was employed to
calculate the dipole moment of isolated molecules, aiming to
enhance accuracy and minimize statistical errors. Each case
involved the analysis of a single, isolated molecule to
determine its corresponding dipole moment.
To ensure robust results, an extensive dataset was
generated, consisting of 109 distinct molecular
configurations for each molecule under investigation. This
comprehensive approach was adopted to significantly
reduce statistical errors and nearly eliminate their impact
on the outcomes.
Following a methodology consistent with our prior
research [4,5], our Molecular Models incorporated various
molecular characteristics such as bonds, angles, and
dihedral angles. These elements were considered crucial for
accurately assessing the interactions occurring between
different sites within each molecule. Additionally, partial
charges were determined using Quantum Mechanical
techniques, a process that had been previously undertaken.
The central innovation of this approach was the ability to
compute dipole moments solely by evaluating interatomic
interactions. Importantly, intermolecular forces, commonly
present in simulations involving multiple molecules within
a simulation cell, were excluded from the calculations. This
focus on interatomic interactions allowed for a more precise
and isolated assessment of the dipole moment's behavior.
It is essential to underscore that while dipole moment
calculations could theoretically be derived from isolated
Quantum Mechanical (QM) computations, these methods
are computationally intensive and time-consuming, even
with modern computing resources. Hence, the methodology
described in this study offers a practical and efficient
alternative to extract dipole moment insights without the
computational burdens associated with QM calculations.
Overall, the methodology employed in this research
uniquely combined isolated molecular analysis,
comprehensive configurations, incorporation of key
molecular characteristics, and Quantum Mechanical
principles to accurately calculate dipole moments. This
approach, by isolating interatomic interactions and
minimizing statistical errors, enables a deeper
understanding of the dipole moment behavior of specific
molecules, ultimately contributing to advancements in our
comprehension of molecular properties and their
interactions.
Figure 1 illustrates earlier endeavors in establishing the
Dipole Moment Vector using data from optimized structures
obtained through the M06-2X/6-311++G(d,p) method. The
vectors' starting points are aligned with the center of mass.
Figure 1a. A-230 Mirzayanov structure and dipole
moment p[11]
Figure 1b. A-232 Mirzayanov structure and dipole
moment [11]
3. Results and discussion
In order to calculate dipole moment, a billion of single
flexible molecule configurations were averaged, as mentioned
above. Equation 1 shows the corresponding relationship and
results are shown in Table 1.
𝜇 = ∑𝑞𝑖𝑟𝑖 (1)
𝑖
Table 1. Dipole Moment Results
Dipole Moment
Dipole Moment for a single molecule
(Debye)
A230
A234
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DOI: 10.37394/232023.2023.3.1
Michail Chalaris, Antonios Koufou, Kalliopi Kravari
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Volume 3, 2023
Mirzayanov
structures
5.459
Ellison-Hoenig
structures
4.234
4. Conclussion
The conclusions drawn from this research paper underscore
the effectiveness and efficiency of the employed technique for
estimating dipole moments, offering a distinct advantage over
the time-consuming Quantum Mechanical (QM) calculations.
The approach adopted in this study represents a statistical
estimation of the dipole moment, providing reliable results while
avoiding the computational demands typically associated with
QM calculations.
A key strength of the methodology lies in its focus on single
molecule simulations. This strategy capitalizes on the rapid
computational capabilities of modern computers, allowing for
swift calculations at each step of the process. The execution of
109 steps, a considerable number of iterations, becomes feasible
within a relatively short timeframe. This computational
efficiency is a notable advantage, enabling the researchers to
perform a significant number of simulations to enhance
accuracy and statistical reliability.
The central premise of the research paper is to calculate and
present the dipole moment of three specific Novichok agents,
considering both of their possible structural forms. By applying
the methodology outlined, the study successfully achieved this
goal. The dipole moment values obtained contribute to a deeper
understanding of the molecular behavior of these agents,
shedding light on their charge distribution and overall polar
nature.
In essence, the research highlights that the proposed
approach offers a viable alternative to QM calculations, which
are often resource-intensive and time-consuming. The emphasis
on single molecule simulations, coupled with the efficiency of
contemporary computing technology, allows for a substantial
number of simulations to be performed promptly. This, in turn,
enabled the researchers to calculate and present the dipole
moments of the selected Novichok agents in both of their
structural forms, thereby advancing our comprehension of these
molecules' characteristics.
In conclusion, the study's technique for dipole moment
estimation represents a significant advancement in
computational chemistry. It not only provides valuable insights
into the properties of Novichok agents but also demonstrates the
potential of streamlined simulation methods in advancing
scientific understanding within a reasonable timeframe.
Acknowledgment
CPU time of GRID Computing Center, which is located at the
International Hellenic University (IHU), Kavala Campus
(Greece), is gratefully acknowledged. This research has received
funding from the European Union´s Erasmus+ Programme:
ERASMUS-EDU-2022-CB-VET call under grant agreement
No 101092458 with the acronym GROWTH.
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Contribution of Individual Authors to the
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Policy)
The authors equally contributed in the present
research, at all stages from the formulation of the
problem to the final findings and solution.
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Scientific Article or Scientific Article Itself
No funding was received for conducting this study.
Conflict of Interest
The authors have no conflicts of interest to declare
that are relevant to the content of this article.
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MOLECULAR SCIENCES AND APPLICATIONS
DOI: 10.37394/232023.2023.3.1
Michail Chalaris, Antonios Koufou, Kalliopi Kravari
E-ISSN: 2732-9992
4
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