Yes / In a competitive coformer exchange reaction, a recent topic of interest in pharmaceutical research, the coformer in a pharmaceutical cocrystal is exchanged with another coformer which is expected to form a cocrystal that is more stable. There will be a competition between coformers to form the most stable product through formation of hydrogen bonds. Thus, to monitor each and every step of such reactions, employing a very sensitive technique is crucial. 1H nuclear magnetic resonance (NMR) is a very powerful technique that is very sensitive to the hydrogen bond interactions. In this study, an in situ monitoring of a coformer exchange reaction is carried out by 1H magic angle spinning (MAS) solid-state NMR (SSNMR) at a spinning frequency of 60 KHz. The changes in caffeine maleic acid cocrystals on addition of glutaric acid, and caffeine glutaric cocrystal on addition of maleic acid were monitored. In all the reactions, it has been observed that caffeine glutaric acid Form I is formed. When glutaric acid was added to 2:1 caffeine maleic acid, the formation of metastable 1:1 caffeine glutaric acid Form I was observed, at the start of the experiment, indicating that the centrifugal pressure is enough for the formation. The difference in the end product of the reactions with similar reaction pathway of 1:1 and 2:1 reactant stoichiometry indicate that a complete replacement of maleic acid has only occurred only in the 1:1 stoichiometry of the reactants. The polymorphic transition of caffeine glutaric acid Form II to Form I at higher temperature was crucial reason which triggers the exchange of glutaric acid with maleic acid in the reaction of caffeine glutaric acid and maleic acid. Based on these results, new reaction pathways in competitive coformer exchange reactions could be distinguished, and the remarkable role of stoichiometry, polymorphism, temperature and centrifugal pressure could be established. / C.H. acknowledges Department of Science and Technology, India (DST), for the grant of Inspire Fellowship. T.G.A. acknowledges Council of Scientific and Industrial Research, India (CSIR) for research grants under the 12th 5 year plan project (Grant No. CSC0405). / The full-text of this article will be released for public view at the end of the publisher embargo on 19 Feb 2025.

Analysis of the molecular speciation of organic compounds in solution is essential for the understanding of ionic complexation. The Raman spectroscopic technique was chosen for this purpose because it allows the identification of compounds in different states and it can give information about the molecular geometry from the analysis of the vibrational spectra. In this research the ionisation steps of relevant pharmaceutical material have been studied by means of potentiometry coupled with Raman spectroscopy; the protonation and deprotonation behaviour of the molecules were studied in different pH regions. The abundance of the different species in the Raman spectra of aqueous salicylic acid, paracetamol, citric acid and salicylaldoxime have been identified, characterised and confirmed by numerical treatment of the observed spectral data using a multiwavelength curve-fitting program. The non-destructive nature of the Raman spectroscopic technique and the success of the application of the multiwavelength curve-fitting program demonstrated in this work have offered a new dimension for the rapid identification and characterisation of pharmaceuticals in solution and have indicated the direction of further research. The work also covers the formation of novel cocrystal systems with pharmaceutically relevant materials. The existence of new cocrystals of salicylic acid-nicotinic acid, DLphenylalanine , 6-hydroxynicotinic acid, and 3,4-dihydroxybenzoic acid with oxalic acid have been identified from stoichiometric mixtures using combined techniques of Raman spectroscopy (dispersive and transmission TRS), X-ray powder diffraction and thermal analysis. Raman spectroscopy has been used to demonstrate a number of important aspects regarding the nature of the molecular interactions in the cocrystal. Cocrystals of salicylic acid - benzamide, citric acid-paracetamol and citric acid -benzamide have been identified with similar analytical approaches and structurally characterised in detail with single crystal X-ray diffraction. From these studies the high selectivity and direct micro sampling of Raman spectroscopy make it possible to identify spectral contributions from each chemical constituent by a peak wavenumber comparison of single-component spectra (API and guest individually) and the two- component sample material (API/guest), thus allowing a direct assessment of cocrystal formation to be made. Correlation of information from Raman spectra have been made to the X-ray diffraction and thermal analysis results. Transmission Raman Spectroscopy has been applied to the study cocrystals for the first time. Identification of new phases of analysis of the low wavenumber Raman bands is demonstrated to be a key advantage of the TRS technique.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-05-08T20:15:35Z No. of bitstreams: 1 FranciscaSilva.pdf: 4464543 bytes, checksum: 4e3dc826f1a161f6f567a3489b8e9fb4 (MD5) / Made available in DSpace on 2017-05-08T20:15:35Z (GMT). No. of bitstreams: 1 FranciscaSilva.pdf: 4464543 bytes, checksum: 4e3dc826f1a161f6f567a3489b8e9fb4 (MD5) Previous issue date: 2016-11-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão (FAPEMA) / Gliclazide (GLZ) is an oral antidiabetic agent used for glycemic control in patients with Diabetes Mellitus Type II (DMII). The GLZ has high membrane permeability and low aqueous solubility, contributing to the reduction of its therapeutic effectiveness. The cocrystals drug synthesis is a form of increasing its water solubility and its bioavailability. This work aimed to synthesize and characterize a novel co-crystal of GLZ using as coformer tromethamine (TRIS). Therefore, it was carried out the computational study using the Gauss 09W software, aiming to study the structural conformation energy of GLZ and TRIS molecules for the investigation of possible interactions between API and coformer. Subsequently, the synthesis of co-crystal GLZ-TRIS (1:1) was performed by liquid-assisted manual grinding and liquid-assisted ball mill grinding process. Subsequently, the co-crystal was characterized by the Powder X-ray diffraction method (PXRD), Fourier Transform Infrared Spectroscopy (FT-IR), Raman Spectroscopy Thermogravimetry and Differential Thermal Analysis Simultaneous (TG-DTA), Differential Scanning Calorimetry (DSC) and fotovisual DSC. Moreover, the stoichiometric ratio of co-crystal was obtained from the construction of the binary phase diagrams using the DSC technique. The computational study showed the major potential energy sites for GLZ and TRIS, serving as a basis for the prediction of possible groups of molecular interaction between the molecules under study. The results obtained by XRPD showed the formation of a new crystalline phase (co-crystal) for the binary mixture of GLZ with TRIS. The binary phase diagram showed the formation of the co-crystal GLZ-TRIS in the molar ratio 1:1. The FTIR and Raman analysis of this co-crystal indicated significant changes in their vibrational modes from which is possible to infer the main sites of interaction by hydrogen bonds involved in the formation of this material. The results of the thermoanalytical study obtained by TG-DTA and DSC showed that the co-crystal presented different thermal properties as compared to the starting compounds, exhibiting intermediate stability to these last compounds. The TG-DTA indicated that the co-crystal has stability until at 150.0 °C. In DSC study, the co-crystal presented a melting point at 144.0 °C, which was confirmed by analysis of fotovisual DSC. In addition, the cyclic DSC showed a crystallization cycle transition in the second heating cycle. Thus, it is concluded that both methods of cocrystallization used in this study yielded in the synthesis of new cocrystal GLZ-TRIS (1:1). These methods presented more advantageous over other methods of cocrystallization, because they require less time of synthesis and less amount of solvent. Therefore, the co-crystal synthesized in this work is presented as a very promising and new pharmaceutical solid form of GLZ for the production of safer and more effective drugs in DMII therapy. / A gliclazida (GLZ) é um antidiabético oral utilizado para o controle da glicemia em pacientes portadores do Diabetes Mellitus Tipo II (DMII). A GLZ possui elevada permeabilidade membranar e baixa solubilidade aquosa, contribuindo para a redução da sua eficácia terapêutica. A síntese de cocristais de fármacos constitui uma forma de aumentar a sua hidrossolubilidade e a sua biodisponibilidade. Assim, este trabalho objetivou sintetizar e caracterizar um novo cocristal de GLZ, utilizando como coformador a trometamina (TRIS). Para tanto, foi realizado o estudo computacional utilizando o software Gauss 09W, visando estudar a conformação estrutural de energia das moléculas de GLZ e TRIS para a investigação das possíveis interações entre o fármaco e o coformador. Posteriormente, a síntese do cocristal de GLZ-TRIS na razão molar de 1:1, foi realizada por moagem líquido-assistida manual e por moagem líquido-assistida via moinho de bolas. Em seguida, o cocristal foi caracterizado por Difração de Raios X pelo método do pó (DRXP), Espectroscopia no Infravermelho com Transformada de Fourier (FTIR), Espectroscopia Raman, Termogravimetria e Análise Térmica Diferencial Simultâneas (TG-DTA), Calorimetria Exploratória Diferencial (DSC) e DSC fotovisual. Além disso, a relação estequiométrica do cocristal foi obtida a partir da construção do diagrama de fases binário, utilizando a técnica de DSC. O estudo computacional mostrou os principais sítios de energia potencial para a GLZ e a TRIS, servindo como base para a predição dos possíveis grupos moleculares de interação entre as moléculas em estudo. Os resultados obtidos por DRXP mostraram a formação de uma nova fase cristalina (cocristal) para a mistura binária de GLZ com a TRIS. O diagrama de fases binário apresentou evidências da formação do cocristal de GLZ-TRIS na razão molar de 1:1. As análises de FTIR e Raman deste cocristal indicaram alterações significativas nos seus modos vibracionais, sendo possível inferir os principais sítios de interação por ligações de hidrogênio envolvidas na formação deste material. Os resultados do estudo termoanalítico obtidos por TG-DTA e por DSC mostraram que o cocristal apresentou propriedades térmicas diferentes dos seus compostos de partida, exibindo estabilidade intermediária a estes compostos. O TG-DTA indicou que o cocristal possui estabilidade até 150°C. No estudo por DSC o cocristal apresentou um ponto de fusão em 144°C, sendo confirmado pela análise de DSC fotovisual. Além disso, o DSC cíclico indicou uma transição de cristalização no segundo ciclo de aquecimento. Assim, conclui-se que ambas as metodologias de cocristalização utilizadas neste estudo resultaram na síntese de um novo cocristal de GLZ-TRIS (1:1). Estas metodologias apresentam-se mais vantajosas em relação a outras metodologias de cocristalização, pois elas requerem menor tempo de síntese e menor quantidade de solvente. Portanto, o cocristal sintetizado neste trabalho apresenta-se como uma nova forma sólida farmacêutica de GLZ muito promissora para a produção de medicamentos mais seguros e eficazes na terapia do DMII.

Analysis of the molecular speciation of organic compounds in solution is essential for the understanding of ionic complexation. The Raman spectroscopic technique was chosen for this purpose because it allows the identification of compounds in different states and it can give information about the molecular geometry from the analysis of the vibrational spectra. In this research the ionisation steps of relevant pharmaceutical material have been studied by means of potentiometry coupled with Raman spectroscopy; the protonation and deprotonation behaviour of the molecules were studied in different pH regions. The abundance of the different species in the Raman spectra of aqueous salicylic acid, paracetamol, citric acid and salicylaldoxime have been identified, characterised and confirmed by numerical treatment of the observed spectral data using a multiwavelength curve-fitting program. The non-destructive nature of the Raman spectroscopic technique and the success of the application of the multiwavelength curve-fitting program demonstrated in this work have offered a new dimension for the rapid identification and characterisation of pharmaceuticals in solution and have indicated the direction of further research. The work also covers the formation of novel cocrystal systems with pharmaceutically relevant materials. The existence of new cocrystals of salicylic acid-nicotinic acid, DLphenylalanine , 6-hydroxynicotinic acid, and 3,4-dihydroxybenzoic acid with oxalic acid have been identified from stoichiometric mixtures using combined techniques of Raman spectroscopy (dispersive and transmission TRS), X-ray powder diffraction and thermal analysis. Raman spectroscopy has been used to demonstrate a number of important aspects regarding the nature of the molecular interactions in the cocrystal. Cocrystals of II salicylic acid ¿ benzamide, citric acid-paracetamol and citric acid -benzamide have been identified with similar analytical approaches and structurally characterised in detail with single crystal X-ray diffraction. From these studies the high selectivity and direct micro sampling of Raman spectroscopy make it possible to identify spectral contributions from each chemical constituent by a peak wavenumber comparison of single-component spectra (API and guest individually) and the two- component sample material (API/guest), thus allowing a direct assessment of cocrystal formation to be made. Correlation of information from Raman spectra have been made to the X-ray diffraction and thermal analysis results. Transmission Raman Spectroscopy has been applied to the study cocrystals for the first time. Identification of new phases of analysis of the low wavenumber Raman bands is demonstrated to be a key advantage of the TRS technique. / Libyan government and Misurata University

A range of small molecules of interest for use in organic semiconductor devices were studied computationally. Trends in geometry, absorption spectra, molecular orbitals, electrostatic potentials, reorganisation energies were studied. Results suggest that, as with acenes, the performance of non-linear cata-condensed polyaromatic hydrocarbons improves as number of fused benzene rings increases. The torsion in these molecules did not appear to have a large impact on the conjugation across the core and little effect on the absorption spectra, although it did affect the reorganisation energies on which charge mobilities depend. Computational studies of mobilities of anthradithiophene molecules were broadly able to reproduce trends seen experimentally and emphasised the importance of crystal morphology. Experimental work was also carried out to search for cocrystals between anthradithiophene derivatives. Many examples were found with some mixtures forming different cocrystals at different mixture ratios. These results were rationalised by a computational study that showed molecules which had a similar binding energy were more likely to be able to form cocrystals. Cocrystal devices were fabricated and 3 out of 7 showed a larger mobility than devices made out of its constituent materials alone. The best of these had a mobility 65% higher than a device made out of the constituent material with the largest mobility. An energy decomposition analysis was carried out on a novel thallophilic system, a complex of thallium with a neutral β-triketimine ligand which was found to form dimers with close Tl-Tl interactions. Calculations show the electrostatic interaction to be repulsive for the dimer with no counter ions, but attractive when 3,5-bistrifluoromethylphenyl borate counter ions are included. This suggests the metallophilic interaction is counter ion-mediated, requiring the anions to provide favourable electrostatics, even in the case of spatially diffuse and distant counter ions such used here. To enable the studies described here software was written for simulating absorption spectra. An implementation into the Gaussian Suite of programs of an energy decomposition scheme and its extension to include an empirical dispersion correction was also carried out.

The aim of this work was formulated - the synthesis of potent human carbonic anhydrase inhibitors, and their structure - activity study. The synthesized 136 new compounds were subjected to the studies of their inhibitory activity towards CA I, II, VII, XII and XIII (VU IBT). An efficient method for N-and S-alkylation of heterocyclic compounds (benzimidazole), S-alkylation of heterocyclic and aromatic compounds (imidazole, benzothiazole, benzimidazothiadiazole, pyrimidine, benzenethiol) with 3 - and 4 - (bromoacetyl)benzenesulfonamides and 4 - and 5 - (bromoacetyl)-2-chlorobenzenesulfonamides has ben deveoped. 2-[(6-oksopyrimidine-2-yl)thio]acetylbenzenesulfonamides in dimethylsulfoxide solution were found to exists in two forms - open chain and cyclic. 4-(Hetarylmethylcarbonyl)benzenesulfonamides exibited more inhibitory potency to CA than the 3-(hetarylmethylcarbonyl)benzenesulfonamides. Among all compound studied S-alkylated benzenethiol derivatives exibit the best CA inhibitory properties, while 1,3-thiazole derivatives – the lowest. Sulfonamide group position on the benzene ring is more important for CA binding than the acidic properties of sulfonamide group. The inhibitors having the selectivity of any one CA were selected from synthesized compounds. Most of the compounds possess selectivity to CA I and CA XIII, while selectivity to CA XII almost is not observed. The benzenesulfonamide ring position in CA II active site is unique to each class of compounds as showed in... [to full text] / Šio darbo tikslas – potencialių žmogaus karboanhidrazių (CA) slopiklių sintezė ir jų struktūros – aktyvumo tyrimas. CA slopinimo tyrimams susintetinti 136 įvairiais heterociklais pakeisti benzensulfonamidai ir išmatuotas jų CA I, II, VI, XII ir XIII slopinimo aktyvumas (VU BTI mokslininkai). Paruoštos efektyvios benzimidazolų N- ir S-alkilinimo, imidazolų, benztiazolo, benzimidazotiadiazolo, pirimidinų, benzenalkiltiolių S-alkilinimo 3- ir 4-(bromacetil)benzensulfonamidais bei 4- ir 5-(bromacetil)-2-chlorbenzensulfonamidais metodikos. Nustatyta, kad [(6-oksopirimidin-2-il)tio]acetilbenzensulfonamidai tirpaluose egzistuoja atviroje ir ciklinėje formose. Ištyrus benzensulfonamidinio ir heterociklinio/aromatinio fragmentų struktūros įtaka CA slopinančioms savybėms nustatyta, kad benzensulfonamidinės dalies įtaka CA slopinančiam aktyvumui yra didesnė nei heterociklinės/aromatinės. Sulfonamidinės grupės padėties benzeno žiede įtaka jungimuisi prie CA yra reikšmingesnė nei sulfonamidinės grupės rūgštingumo įtaka. Tiriant atrankumą vienai CA nustatyta, kad iš visų junginių daugiausiai atrankių yra CA I ir XIII, o CA XII atrankių junginių beveik nėra. Daugiausiai kuriai nors CA atrankių junginių yra tarp 4-(hetarilmetilkarbonil)benzensulfonamidų, bei tarp 1,3-tiazolo ir benzenalkiltiolio darinių. Remiantis rentgenostruktūrine CA II, XII ir XIII kompleksų (VU BTI) su kai kuriais slopikliais analize, paaiškintas sumažėjęs junginių giminingumas CA XII, lyginant su CA II, sumažėjęs... [toliau žr. visą tekstą]

Šio darbo tikslas – potencialių žmogaus karboanhidrazių (CA) slopiklių sintezė ir jų struktūros – aktyvumo tyrimas. CA slopinimo tyrimams susintetinti 136 įvairiais heterociklais pakeisti benzensulfonamidai ir išmatuotas jų CA I, II, VI, XII ir XIII slopinimo aktyvumas (VU BTI mokslininkai). Paruoštos efektyvios benzimidazolų N- ir S-alkilinimo, imidazolų, benztiazolo, benzimidazotiadiazolo, pirimidinų, benzenalkiltiolių S-alkilinimo 3- ir 4-(bromacetil)benzensulfonamidais bei 4- ir 5-(bromacetil)-2-chlorbenzensulfonamidais metodikos. Nustatyta, kad [(6-oksopirimidin-2-il)tio]acetilbenzensulfonamidai tirpaluose egzistuoja atviroje ir ciklinėje formose. Ištyrus benzensulfonamidinio ir heterociklinio/aromatinio fragmentų struktūros įtaka CA slopinančioms savybėms nustatyta, kad benzensulfonamidinės dalies įtaka CA slopinančiam aktyvumui yra didesnė nei heterociklinės/aromatinės. Sulfonamidinės grupės padėties benzeno žiede įtaka jungimuisi prie CA yra reikšmingesnė nei sulfonamidinės grupės rūgštingumo įtaka. Tiriant atrankumą vienai CA nustatyta, kad iš visų junginių daugiausiai atrankių yra CA I ir XIII, o CA XII atrankių junginių beveik nėra. Daugiausiai kuriai nors CA atrankių junginių yra tarp 4-(hetarilmetilkarbonil)benzensulfonamidų, bei tarp 1,3-tiazolo ir benzenalkiltiolio darinių. Remiantis rentgenostruktūrine CA II, XII ir XIII kompleksų (VU BTI) su kai kuriais slopikliais analize, paaiškintas sumažėjęs junginių giminingumas CA XII, lyginant su CA II, sumažėjęs... [toliau žr. visą tekstą] / The aim of this work was formulated - the synthesis of potent human carbonic anhydrase inhibitors, and their structure - activity study. The synthesized 136 new compounds were subjected to the studies of their inhibitory activity towards CA I, II, VII, XII and XIII (VU IBT). An efficient method for N-and S-alkylation of heterocyclic compounds (benzimidazole), S-alkylation of heterocyclic and aromatic compounds (imidazole, benzothiazole, benzimidazothiadiazole, pyrimidine, benzenethiol) with 3 - and 4 - (bromoacetyl)benzenesulfonamides and 4 - and 5 - (bromoacetyl)-2-chlorobenzenesulfonamides has ben deveoped. 2-[(6-oksopyrimidine-2-yl)thio]acetylbenzenesulfonamides in dimethylsulfoxide solution were found to exists in two forms - open chain and cyclic. 4-(Hetarylmethylcarbonyl)benzenesulfonamides exibited more inhibitory potency to CA than the 3-(hetarylmethylcarbonyl)benzenesulfonamides. Among all compound studied S-alkylated benzenethiol derivatives exibit the best CA inhibitory properties, while 1,3-thiazole derivatives – the lowest. Sulfonamide group position on the benzene ring is more important for CA binding than the acidic properties of sulfonamide group. The inhibitors having the selectivity of any one CA were selected from synthesized compounds. Most of the compounds possess selectivity to CA I and CA XIII, while selectivity to CA XII almost is not observed. The benzenesulfonamide ring position in CA II active site is unique to each class of compounds as showed in... [to full text]

Submitted by Alison Vanceto (alison-vanceto@hotmail.com) on 2017-02-16T16:22:40Z No. of bitstreams: 1 DissBCDO.pdf: 4309058 bytes, checksum: 4f5cf3d0dbedd0e22b67ee37cbc653e9 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-03-13T18:12:23Z (GMT) No. of bitstreams: 1 DissBCDO.pdf: 4309058 bytes, checksum: 4f5cf3d0dbedd0e22b67ee37cbc653e9 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-03-13T18:12:35Z (GMT) No. of bitstreams: 1 DissBCDO.pdf: 4309058 bytes, checksum: 4f5cf3d0dbedd0e22b67ee37cbc653e9 (MD5) / Made available in DSpace on 2017-03-13T18:20:51Z (GMT). No. of bitstreams: 1 DissBCDO.pdf: 4309058 bytes, checksum: 4f5cf3d0dbedd0e22b67ee37cbc653e9 (MD5) Previous issue date: 2015-09-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Pharmaceutical cocrystals are multicomponent crystalline solids comprised of an active pharmaceutical ingredient (API) and one or more co-formers interacting through hydrogen bonding or other weak interactions like the π-stack and van der Waals interactions. Fluconazole (FLZ) is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. It is also used to prevent and treat meningitis. Cocrystallization is an alternative approach for enhancement of drug. It can be performed using neat grinding, solvent assisted grinding, solvent evaporation, cooling evaporation and slurry cocrystallization. In this work, a new cocrystal Fluconazol-Fumaric acid monohydrate was synthesized via 1:1 stoichiometric amount of FLZ and FUM at different conditions. The characterization of the synthesized cocrystals was achieved using Raman spectroscopy, differential scanning calorimetry, powder X-ray diffraction and single crystal X-ray diffraction. The results obtained for the characterization of the samples showed some obvious differences among the spectra, diffractograms and thermograms. The single crystal X-ray diffraction analysis of the new structure shows a cocrystal where the fluconazole molecules are attached to the fumaric acid and water molecules respectively through hydrogen bonds, gave unique cell dimensions for an assumed structure C17H18F2N6O6 with a space group of P21/n, a = 17.053(3) Å, b = 5.5995(10), c=21.154(3), α = 90°, β=105.418(4)°, γ= 90°, V = 1947.3(6) Å3. This work is the first to report a monohydrate cocrystal structure of fluconazole and fumaric acid. / Cocristais farmacêuticos são sólidos cristalinos multi-componentes compostos de um ingrediente ativo farmacêutico (API) e um ou mais co-formadores interagindo através de ligações de hidrogênio ou outras interações fracas como as π-stack e Van der Waals. Fluconazol (FLZ), é um fármaco anti-fúngico triazol utilizado no tratamento e prevenção de infecções fúngicas superficiais e sistémicas. É também utilizado para prevenir e tratar a meningite. Cocristalização é uma abordagem alternativa para melhorar as propriedades de fármacos. Pode ser realizada através de moagem a seco, moagem assistida por solvente, evaporação de solvente e cristalização em suspensão. Neste trabalho, um novo co-cristal Fluconazol-Ácido Fumarico monohidrato foi sintetizado utilizando uma estequimetria 1:1 em diferentes condições. A caracterização dos co-cristais sintetizados foi realizada utilizando espectroscopia Raman, calorimetria exploratória diferencial, difração de raios-X em pó é por monocristal. Os resultados obtidos para a caracterização das amostras mostrou algumas diferenças obvias entre os espectros, difratogramas e termogramas. A difração de raios-X de monocristal mostrou uma nova estrutura onde as moléculas de fluconazol estão ligadas ao ácido fumárico e a uma molécula de água através de ligações de hidrogênio, originando uma estrutura única C17H18F2N6O6 de grupo espacial P21/n e dimensões da célula unitária a = 17.053(3) Å, b = 5.5995(10), c=21.154(3), α = 90°, β=105.418(4)°, γ= 90°, V = 1947.3(6) Å3. Este trabalho é o primeiro a relatar uma estrutura de co-cristal mono-hidrato de fluconazol e acido fumárico.