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Physicochemical Characteristics of Dibromobenzimidazole Derivatives

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Abstract

At the initial stage of the design of a medicinal substance the physicochemical characteristics of the active pharmaceutical ingredient is essential. Preformulation of the active substances aims to minimize the problems associated with obtaining the proper formulation in subsequent stages of drug development, reduction the costs of drug research and optimization the time for the transition from active substance to drug form and reaching to the market. This paper contains the pathway of synthesis of selected dibromobenzimidazole derivatives and their physicochemical characteristics. The selected group contained three dibromobenzimidazole derivatives differing in type, size, and polarity of substituents in N-1 and C-2 positions of the benzimidazole core. The examined substances were: (5,6-dibromo-1H-benzimidazol-1-yl)acetonitrile (DB1), 2-(5,6-dibromo-1H-benzimidazol-1-yl)-1-(4-fluorophenyl)ethanone (DB2), [5,6-dibromo-2-(trifluoromethyl)-1H-benzimidazol-1-yl]acetonitrile (DB3). The physicochemical characteristics consist of thermal analyses, solubilities, and ionization constants. Thermal analyses were performed using differential scanning calorimetry. Solubilities of the substances were determined in water, ethanol, and 1-octanol at atmospheric pressure. The experimental results were correlated with thermodynamic models based on local concentration theory. The spectrophotometric method was used to determine ionization constants at temperatures 298.2 K and 310.2 K.

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Abbreviations

D :

Absorbance value

ΔfusH:

Molar enthalpy of fusion (kJ·mol−1)

p :

Pressure

p(aHγCl):

Acidity function

pK a :

Acidity function

T :

Equilibrium temperature (K)

∆T :

Estimated error of temperature (K)

x :

Mole fraction

\({V}_{m}^{{298} K}\) :

Molar volume at the temperature 293.2 K

γ :

Activity coefficient

\({\sigma }_{T}\) :

Root-mean-square deviation in temperature

A:

Base value

cal:

Calculated value

exp:

Experimental value

HA:

Acid value

fus:

Fusion

lit:

Literature data

T :

Temperature

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Acknowledgements

Funding for this research was provided by the Warsaw University of Technology, Warsaw, Poland.

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Authors and Affiliations

  1. Department of Physical Chemistry, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664, Warsaw, Poland

    Agnieszka Śliwińska & Aneta Pobudkowska

  2. Department of Biotechnology of Medicines and Cosmetics, Faculty of Chemistry, Warsaw University of Technology, Koszykowa 75, 00-662, Warsaw, Poland

    Anna Kowalkowska

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  1. Agnieszka Śliwińska
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Correspondence to Aneta Pobudkowska.

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Śliwińska, A., Pobudkowska, A. & Kowalkowska, A. Physicochemical Characteristics of Dibromobenzimidazole Derivatives. J Solution Chem 51, 556–576 (2022). https://doi.org/10.1007/s10953-022-01153-3

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