Int. J. Chem. Technol. 2020, 4 (1), 60-70 Kandemirli and co-workers DOI: http://dx.doi.org/10.32571/ijct.712499 E-ISSN:2602-277X International Journal of Chemistry and Technology http://dergipark.org.tr/ijct Research Article Theoretical B3LYP study of contrast agent metrizoate 1 2,* 2 3 S. Giray KANDEMIRLI , M. Izzettin YILMAZER , Murat SARACOGLU , Fatma KANDEMIRLI 1Department of Radiology, Roy Carver College of Medicine, University of Iowa, United States 2Faculty of Education, Erciyes University, 38039, Kayseri, Turkey 3Biomedical Engineering Department, Faculty of Engineering and Architecture, Kastamonu University, 37150, Kastamonu, Turkey Received: 01 April 2020; Revised: 12 May 2020; Accepted: 15 May 2020 *Corresponding author e-mail: [email protected] Citation: Kandemirli, S.G.; Yılmazer, M. I.; Saraçoğlu, M.; Kandemirli, F. Int. J. Chem. Technol. 2020, 4 (1), 60-70. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ ABSTRACT Kontrast maddesi metrizoatın teorik B3LYP Metrizoic acid is a molecule used as meglumine metrizoate, incelemsi sodium metrizoate contrast agent. 6 Isopak 44o* is a contrast medium containing a mixture of sodium, calcium, magnesium ÖZ and N-methylglucamine salts of metrizoic acid. In order to determine the reactivity properties of metrizoic acid, Metrizoik asit, meglumin metrizoat, sodyum metrizoat melagnomie, anionic form of metrizoate, Metrisoate K, kontrast maddesi olarak kullanılan bir moleküldür. 6 izopak metrizoate-melagnomie salt, and Na-metrizoate, DFT 44o*, metrizoik asidin sodyum, kalsiyum, magnezyum ve N- calculations were made in gas and water phses at the level of metilglukamin tuzlarının bir karışımını içeren bir kontrast B3LYP/LANL2DZ with the help of Gaussian 09 software. ortamıdır. Metrizoik asit, melagnomi, anyonik metrizoat Some global chemical reactivity descriptors such as highest formu, metrisoate K, metrizoate-melagnomie tuzu ve Na- occupied molecular orbital energy, lowest empty molecular metrizoate formunun reaktivite özelliklerini belirlemek için orbital energy, absolute hardness, chemical potential, softness, gaz ve su fazında B3LYP / LANL2DZ seviyesinde Gaussian electronegativity, chemical potential, global electrophilicity 09 yazılımı yardımıyla DFT hesaplamaları yapıldı. En yüksek and electrofugality were calculated. Moreover, nonlinear işgal edilen moleküler orbital enerji, en düşük boş moleküler optical properties of the title compound were calculated too. In orbital enerji, mutlak sertlik, kimyasal potansiyel, yumuşaklık, addition, thermodynamic properties of the molecules elektronegatiflik, kimyasal potansiyel, küresel elektrofiliklik, examined at different temperatures were calculated in gas and nükleojenite ve elektrofugalite gibi bazı küresel kimyasal water phases. The findings of this study, obtained from reaktivite tanımlayıcıları hesaplandı. Ayrıca, bileşiğin lineer extensive and time-consuming calculations and analyses, will olmayan optik özellikleri de hesaplandı. Bunun yanında farklı be an important source of information for the preparation of sıcaklıklarda incelenen moleküllerin termodinamik özellikleri the drug combination in the future. gaz ve su fazlarında hesaplandı. Kapsamlı ve zaman alan hesaplama ve analizlerden elde edilen bu çalışmanın bulguları, gelecekte ilaç kombinasyonunun hazırlanması için önemli bir bilgi kaynağı olacaktır. Keywords: Metrizoate, DFT, B3LYP, quantum chemical calculations. Anahtar Kelimeler: Metrizoate, DFT, B3LYP, kuantum kimyasal hesaplamalar. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 1. INTRODUCTION because of their higher density and higher atomic number, but gaseous contrast agents absorb fewer X-ray The basic principle is the application of contrast agents than tissues because of their low density, even though in a way that changes the absorption of specific the effective atomic number may be higher. anatomical structures relative to the x-ray environment. Positive contrast agents are iodine or barium The basic building block of iodized contrast agents is a compounds, and negative contrast agents are gases. benzene ring, which has three iodine molecules attached Positive contrast agents absorb more x-rays than tissues to positions 2, 4 and 6. Side chains at positions 3 and 5 60 Int. J. Chem. Technol. 2020, 4 (1), 60-70 Kandemirli and co-workers DOI: http://dx.doi.org/10.32571/ijct.712499 E-ISSN:2602-277X are modified with hydroxyl groups or other molecules Cerebral computed tomography has been performed in that further define the properties of an agent. They can 60 patients who applied for screening before and after be classified into two groups as ionic and non-ionic contrast. Non-ionic contrast agent, iohexol, and an ionic contrast agents depending on whether they are contrast agent sodium metrizoate have been randomly dissociated in solution. Contrast agents can be classified administered to the patients as a contrast agent. Very according to osmality values. Those with ≥ 1400 minor side effects have been recorded with both iohexol mOsm/kg are classified as high osmolar, those with and metrizoate, but iohexol causes much less discomfort 780-800 mOsm/kg as low osmases and those with than metrizoate. It has been reported that there is no approximately 300 mOsm/kg are classified as iso- difference in the development of normal intracranial osmolar agents. structures.6 Isopaque 44o* is a contrast medium which contains a mixture of the sodium, calcium, magnesium, Three properties that define the physical properties of and N-methylglucamine salts of metrizoic acid. iodinated contrast agents-ionicity, osmolality and Theoretical studies on the constructional features of viscosity play a separate role in tolerance and adverse metrizoate are seldom found in literature. In order to reaction profiles.1 interpret molecular properties of metrizoic acid (MetA), melagnomie (Melag), anionic form of metrizoate (an- Pattinson and co-workers2 reported that sodium Met), metrisoate K (K-Met), metrizoate-melagnomie salt amidotrizoate showed certain advantages over the (Melag-Met), Na-metrizoate (Na-Met), theoretical contrast media which they had previously used for studies are needed on the electronic and thermodynamic angiocardiography. And also they found that high flow properties of molecules. B3LYP functional of quantum rates had been achieved with triosil 75% resulting in a chemical calculation methods is widely used in studying great improvement in the quality of the both physical and chemical properties of molecules.7 angiocardiograms when small catheters had been used. In this study, thermodynamic properties and frontier Emergency urography has been performed using either molecular orbitals were theoretically calculated for the low osniolar nonionic (iohexol) or high osmolar ionic MetA, Melag, an-Met, K-Met, Melag-Met, Na-Met. (metrizoat) contrast agent. In 56 percent of all children, Polarizability, hyperpolarizability and some parameters the pain has increased after injection of contrast related to HOMO and LUMO energies were medium. The increase in pain occurs without any investigated using B3LYP/LANLZDZ basis set. difference between the contrast agent and the degree of pain and the number of patients who experience an 2. CALCULATION METHODS increasing pain.3 Structural parameters for each molecule were optimized Ten radiographic contrast agents containing iodine have for at the B3LYP method of Gaussian Program,8 been tested to assess whether there are a rapid, Becke’s three parameter hybrid functional combined continuous and reversible inhibition of thyroxine (T4) with the gradient correlation functional of Lee, Yang secretion from perfused canine thyroid lobes. All of four and Parr (LYP), denoted B3LYP, in the computations agents used for cholecystography (iocetamate, using DFT/LANL2DZ level of theory, and the harmonic iodipamide, oglycamate and iotroxate) cause rapid vibrational frequencies and zero-point vibrational inhibition of T4 secretion from TSH-induced perfused energies (ZPVE) were computed at the same level. canine thyroid lobes, while amidotrizoate, metrizamide, Throughout this paper, all calculations for B3LYP metrizoate, iodamide, diodone and iodamide, optimization of molecular geometry were carried out significantly impressed. All cholecystographic agents with B3LYP/LANL2DZ Opt. Freq. “Opt Freq” means have been reported to inhibit T4 deiodinases from that the frequency was calculated after optimization. canine thyroid and liver.4 The values of the absolute electron negativity (χ), the In a double-blind, randomized, two-group study with 99 chemical potential (μi), the absolute hardness (η), and “high-risk” patients with essentially coronary artery the softness (, the inverse of the hardness), global disease, the nonionic contrast agent, amipak electrophilicity (), nucleofugality (ΔEn) and (metrizamide), have been compared to the ionic medium electrofugality (ΔEe) related with the HOMO and isopaque coronar (meglumine-Na-Ca-metrizoate) in LUMO energies can be determined by Equations (1-10). inecardioangiography and they reported that the patients with a basal LVEDP above 15 mmHg, no significant ( ) (1) change has occurred in LVEDP after left ventriculography with any of the 2 contrast media. It has 5 (2) been reported