INTRODUCTION: THE EQUILIBRIUM CONSTANT IS AN IMPORTANT PHYSICO CHEMICAL PARAMETER OF AS SUBSTANCE AND DETERMINATION OF THE ACIDITY/BASICITY OF CHEMICAL COMPOUNDS IS MATTER OF GENERAL INTEREST FOR CHEMIST AS WELL AS A MATTER OF PARTICAL INTEREST FOR CHEMICAL AND PHARMACEUTICAL INDUSTRIES. [1] HYDROXAMIC ACIDS HAVE BEEN AN INTERESTING AREA OF RESEARCH IN CHEMISTRY DUE TO THEIR IMPORTANT CHEMICAL PROPERTIES [2]. IN THIS WORK, CALCULATION OF THE PK A VALUES FOR THE DERIVATIVES HYDROXAMIC ACID INCLUDING THE FORMO, CHLORO, BROMO, DICHLORO, DIBROMO HYDROXAMIC ARE REPORTED.

IN THIS WORK, CALCULATIONS OF PKA VALUES HAVE BEEN PERFORMED ON THE FLUNITRAZEPAM, CLONAZEPAM AND NITRAZEPAM DRUGS IN AQUEOUS SOLVENT. GAS-PHASE ENERGIES WERE CALCULATED BY PBE1PBE/6-311+G(D,P) LEVEL OF THEORY. ...

ONE OF THE MOST IMPORTANT PROPERTIES OF THE DYES AS THE INDICATOR IS THE DISSOCIATION CONSTANT (PKA). THE PKA VALUES OF DYES CAN BE MEASURED BY DIFFERENT EXPERIMENTAL METHODS BUT THIS TASK IS NOT ALWAYS PRACTICAL. QUANTUM CHEMICAL METHODS HAVE BEEN PROVEN TO BE USEFUL FOR PREDICTING THESE KINDS OF CHEMICAL PROPERTIES EVEN AT A QUANTITATIVE LEVEL. IN ADDITION, A GOOD CORRELATION BETWEEN THEORETICAL AND EXPERIMENTAL DATA ALLOWS THE DEVELOPMENT OF MODELS FOR DETERMINING THE PKA OF DRUGS FOR WHICH EXPERIMENTAL DATA IS NOT YET AVAILABLE [1-3]...

THE DISSOCIATION CONSTANTS AND PROTON-TRANSFER REACTIONS ARE IMPORTANT NOT ONLY IN CHEMISTRY BUT ALSO IN OTHER BRANCHES OF SCIENCE SUCH AS BIOLOGY, MEDICINE, AND FOOD INDUSTRY [1]. MOST DRUGS ARE WEAK ACIDS OR BASES AND PRESENT IN SOLUTION AS BOTH THE IONIZED AND NONIONIZED SPECIES. IN THIS REGARD, DETERMINATION OF PKA VALUES IS VERY IMPORTANT. THE PKA VALUES ARE MEASURED BY DIFFERENT EXPERIMENTAL METHODS BUT THE EXPERIMENTAL MEASUREMENTS OF THE PKA OF DRUGS ARE NOT ALWAYS PRACTICAL AND CAN BE IMPOSSIBLE [2, 3]. THUS, AN ALTERNATIVE COMPUTATIONAL APPROACH IS NEEDED.

THE SULFONAMIDE–SO2NH– GROUP EXISTS IN NUMEROUS BIOLOGICALLY ACTIVE COMPOUNDS, WHICH INCLUDE ANTIMICROBIAL DRUGS, SALURETICS, CARBONIC ANHYDRASE INHIBITORS, INSULIN-RELEASING SULFONAMIDES, ANTITHYROIDAGENTS ANTITUMOR DRUGS. SULFACETAMIDE IS A SULFONAMIDE ANTIBIOTIC THAT BLOCKS THE SYNTHESIS OF DIHYDROFOLIC ACID BY INHIBITING THE ENZYME DIHYDROPTEROATE SYNTHASE. SULFACETAMIDE IS A COMPETITIVE INHIBITOR OF BACTERIAL PARA-AMINOBENZOIC ACID (PABA), WHICH IS REQUIRED FOR BACTERIAL SYNTHESIS OF FOLIC ACID [1]. THE ACID-BASE PROPERTIES OF THESE COMPOUNDS ARE BELIEVED TO PLAY AN IMPORTANT ROLE IN THEIR BIOLOGICAL ACTIVITIES. SULFACETAMIDE HAS AN–NH2 GROUP AND–NHCOCH3 GROUP WHICH PRESENT BASIC AND ACIDIC PROPERTIES, RESPECTIVELY. THIS MOLECULE ALSO HAS A CHANCE TO BE IN THE FORM OF ZWITTERION.IN THE PRESENT RESEARCH, WE STUDIED THEORETICALLY THE STABILITY OF SULFACETAMIDE IN DIFFERENT FORMS IN BOTH GAS-PHASE AND AQUEOUS SOLUTION. WE FOUND THAT ZWITTERION IS NOT THE MOST STABLE FORM FOR THIS MOLECULE. THE ACIDITY AND BASICITY OF THIS COMPOUND HAVE BEEN ALSO INVESTIGATED. THE THEORETICAL PKA OF THIS MOLECULES HAS BEEN CALCULATED AS 4.9 WHICH IS IN AGREEMENT WITH THE EXPERIMENTAL VALUE OF 5.4 [2].IN THIS WORK, STANDARD AB INITIO MOLECULAR ORBITAL THEORY AND DENSITY FUNCTIONAL THEORY CALCULATIONS WERE CARRIED OUT USING THE GAUSSIAN 09 SOFTWARE. GEOMETRIES OF ALL SPECIES WERE OPTIMIZED AT THE B3LYP/6-31G (D) LEVEL OF THEORY, AND WHERE NECESSARY, EXTRA CARE WAS TAKEN TO SELECT THE MINIMUM-ENERGY CONFORMATION VIA SYSTEMATIC CONFORMATIONAL SEARCHING AT THIS LEVEL. THE NATURE OF EACH STATIONARY POINT WAS ESTABLISHED VIA B3LYP/6-31G (D) FREQUENCY CALCULATIONS. THE OPTIMIZED GEOMETRIES HAVE BEEN USED FOR FURTHER CALCULATIONS. FOR CALCULATION OF ENERGIES, ENTHALPIES AND GIBBS ENERGIES, G3 (MP2) //B3LYP [3] HAS BEEN USED ALONG WITH AVAILABLE SOLVATION MODELS OF CPCM AND SMD [4].

A GRAPHENE MODIFIED CARBON PASTE ELECTRODE (GR-CPE) WAS USED FOR DETERMINATION OF DIAZABICYCLO OCTANE, DABCO, AT PH=10.5 OF PHOSPHATE BUFFER SOLUTIONS (PBS). THE CHARACTERIZATION OF THE BARE AND MODIFIED ELECTRODES WAS PERFORMED BY ELECTROCHEMICAL IMPEDANCE SPECTROSCOPY (EIS). DENSITY FUNCTIONAL THEORY (DFT) METHOD AT B3LYP/6-311++G** LEVEL OF THEORY WAS USED TO CALCULATE THE PKA VALUE OF DABCO. ...