The
preparation of cocrystals from active pharmaceutical ingredients
(APIs) and biologically relevant coformers offers the opportunity
of obtaining compounds with more desirable physicochemical and biological
properties. This work focuses on theophylline–trimesic
acid, caffeine–isophthalic acid, and caffeine–trimesic
acid cocrystals. All the cocrystals were produced via slow evaporation
and were characterized using Fourier transform infrared, differential
scanning calorimetry, thermogravimetric analysis, and single-crystal
X-ray diffraction. Structural characterization revealed that interactions
such as CO···H, N···H···O,
π–π, and C–H···π between
the APIs and coformers significantly contribute to crystal packing.
Density functional theory studies further revealed the electronic
properties of cocrystals, as well as the functional groups that enhance
their solubility. Drug activity through the weak groove-binding mode
was realized through docking studies of the cocrystals with the DNA
structure (Protein Data Bank identifier 1ZEW). Similarly, major interactions, including
hydrogen bonding and π-π bonding, were observed between
cocrystals and 4HL2, a New Delhi metallo-β-lactamase-1 produced
by resistant clinical strains of K. pneumoniae. Biological
studies revealed cocrystals with antimicrobial properties, particularly
against clinically relevant gram-negative bacterial pathogens (Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas
aeruginosa). So, these compounds represent a novel promising
group of anti-infective agents.
The reaction of Fe(TPP)N3 with imidazole (Him) and (V-methylimidazole (Melm) has been studied in acetone and dichloromethane. Kinetic measurements at room temperature as well as low-temperature spectroscopic, conductivity, and electrochemical studies were used to fully characterize the intermediate complex Fe(TPP)(RIm)N3 as six-coordinate and low spin. This complex reacts further to give Fe(TPP)(RIm)2+N3~. The rate-limiting step in the overall reaction is azide ionization from Fe(TPP)(RIm)N3 to give the high-spin Fe(TPP)(RIm)+N3". The activation free energy of this step is ca. 3 kcal lower with Him compared to that with Melm because of hydrogen bonding to the departing azide ion in the transition state; this acceleration via hydrogen bonding is an entropic effect. A detailed comparison of M(Por)X systems is presented for M = Fe and Co, Por = TPP, PPIX, and PPIXDME, and X = F", Cl', Br, and N3". The importance of spin changes on the kinetics and thermodynamics of intermediate and product formation is quantified. Hydrogen-bonding effects are found to have a greater influence on the kinetics than on the thermodynamics. The spin change for the reaction Fe(TPP)(RIm)N3 -* Fe(TPP)(RIm)+N3" is S' = *11 11/2 -* s/2, and this is manifested in loss of CFSE (large AH*) and a AS* about 15 cal deg"1 mol"1 more positive than those found for analogous metalloporphyrin reactions that do not feature a spin change.
In the search for new `sulfa drugs' with therapeutic properties, o-nitrosulfonamides and N-cycloamino-o-sulfanilamides were synthesized and characterized using techniques including 1H NMR, 13C NMR and FT–IR spectroscopy, and single-crystal X-ray diffraction (SC-XRD). The calculated density functional theory (DFT)-optimized geometry of the molecules showed similar conformations to those obtained by SC-XRD. Molecular docking of N-piperidinyl-o-sulfanilamide and N-indolinyl-o-sulfanilamide supports the notion that o-sulfanilamides are able to bind to human carbonic anhydrase II and IX inhibitors (hCA II and IX; PDB entries 4iwz and 5fl4). Hirshfeld surface analyses and DFT studies of three o-nitrosulfonamides {1-[(2-nitrophenyl)sulfonyl]pyrrolidine, C10H12N2O4S, 1, 1-[(2-nitrophenyl)sulfonyl]piperidine, C11H14N2O4S, 2, and 1-[(2-nitrophenyl)sulfonyl]-2,3-dihydro-1H-indole, C14H12N2O4S, 3} and three N-cycloamino-o-sulfanilamides [2-(pyrrolidine-1-sulfonyl)aniline, C10H14N2O2S, 4, 2-(piperidine-1-sulfonyl)aniline, C11H16N2O2S, 5, and 2-(2,3-dihydro-1H-indole-1-sulfonyl)aniline, C14H14N2O2S, 6] suggested that forces such as hydrogen bonding and π–π interactions hold molecules together and further showed that charge transfer could promote bioactivity and the ability to form biological interactions at the piperidinyl and phenyl moieties.
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