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 CO···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.

Mixed-ligand Cu(ii) complexes of the type [Cu(doxycycline)(L)(H2O)2](NO3)2, where doxycycline = [4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide] and L = 2,2'-bipyridine (bpy, 1), 1,10-phenanthroline (phen, 2), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 3) and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 4) have been synthesised and characterised by structural, analytical, and spectral methods. The single-crystal X-ray structures of 1 and 2 exhibited two different geometries, distorted square-pyramidal and octahedral respectively as well as different coordination modes of doxycycline. Complexes 2-4 exhibit prominent plasmid DNA cleavage at significantly low concentrations probably by an oxidative mechanism. Matrix Metalloproteinase (MMP-2) inhibition studies revealed that all complexes inhibit MMP-2 similar to doxycycline which is a well-known MMP inhibitor with 3 being the most potent. IC50 values of doxycycline and 1-4 against MCF-7 (human breast cancer) and HeLa cell lines were almost equal in which 3 showed the highest efficiency (IC50 = 0.46 ± 0.05 μM), being consistent with its increased MMP inhibition potency. The antimalarial activities of these complexes against the chloroquine-sensitive Plasmodium falciparum NF54 and chloroquine-resistant Plasmodium falciparum Dd2 strains reveal that complex 3 exhibited a higher activity than artesunate drug against the chloroquine-resistant Dd2 strain.

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In the present study, we have described the synthesis and characterisation of the theophylline hydrate (Theo hydrate), cocrystal (Theo–Phen·2H2O) and hydrated sodium co-crystal of theophylline (Na–(Theo)2ClO·2H2O), where Theo = theophylline and Phen = 1,10-phenathroline.

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The reduction of cis-[CoIII(κ2N,N′-1,10-phenanthroline-5,6-dione)2Cl2]Cl into the neutral compound cis-[CoII(κ2N,N′-1,10-phenanthroline-5,6-dione)2Cl2] was observed during developmental studies of new antimalarial drugs. The crystal structure of cis-[CoII(κ2N,N′-1,10-phenanthroline-5,6-dione)2Cl2] was unveiled by powder X-ray diffraction studies (PXRD). PXRD details, unit cell parameters, and space group for cis-[CoII(κ2N,N′-1,10-phenanthroline-5,6-dione)2Cl2], C24H12Cl2CoN4O4, are reported [a = 41.4951 (13) Å, b = 8.2768 (2) Å, c = 12.4994 (3) Å, unit cell volume V = 4292.9 (2) Å3, Z = 8, and space group Fdd2]. Infrared spectroscopy features are also discussed.

Co-crystals have become an area of research interest for pharmaceutical drug improvements due to their characteristic nature in modifying the physico-chemical properties of active pharmaceutical ingredients (APIs) with the aid of a co-former. Co-crystals improve the solubility, dissolution rate, melting point, and stability of the API without changing the chemical identity nor diminishing the biological activity or the therapeutic effect of the API. This work reports the green synthetic approach to synthesize Diclofenac-Urea (DUREA) co-crystal using a benign solvent and stirring at room temperature, all in an environmentally friendly manner. The synthesis of DUREA was accomplished by reaction of a 1:1 molar ratio of diclofenac potassium and urea and the product gave a white crystalline compound with an excellent yield (91%). The product (DUREA) was structurally characterized using melting point, UV/VIS, and FT-IR spectrophotometry. The antimicrobial activity of the co-crystal was tested against Salmonella typi and Proteus mirablis.

Three manganese complexes of the antibiotic doxycyline viz.: manganese doxycyline, [MnDox2]Cl2‧2H2O (1), and manganese doxycyline with bipyridine, [MnDox2(bpy)]Cl2‧8H2O (2), and phenanthroline, [MnDox2(phen)]Cl2‧8H2O (3), as the ancillary ligand were synthesized and characterized by FT-IR, elemental analysis and electrospray mass spectroscopy. The three complexes show good solubility in DMF and DMSO. Data obtained from spectroscopic techniques used show that doxycycline coordinates to the central manganese atom through the oxygen of the amide group and the carbonyl oxygen atom of ring A while bipyridine/phenanthroline coordinates through the two diimine nitrogen atoms. The stoichiometry of manganese-doxycycline is 1:2 and octahedral geometry is the preferred coordination in all the complexes.