Enhancing physicochemical properties of hydrochlorothiazide with zwitterionic L-proline and 5-fluorocytosine cocrystals through mechanochemical synthesis.

Hydrochlorothiazide (HTZ) is a thiazide-type diuretic drug approved by the FDA in 1959 for treatment of hypertension and peripheral edema and has been used since. HTZ exhibits low solubility and low permeability, leading to variable oral bioavailability and limited intestinal drug permeability. For this reason, several attempts to improve HTZ physicochemical properties have been made during the past decades.

Measurement of Covalent Bond Formation in Light-Curing Hydrogels Predicts Physical Stability under Flow.

Photo-crosslinking hydrogels are promising for tissue engineering and regenerative medicine, but challenges in reaction monitoring often leave their optimization subject to trial and error. The stability of crosslinked gels under fluid flow, as in the case of a microfluidic device, is particularly challenging to predict, both because of obstacles inherent to solid-state macromolecular analysis that prevent accurate chemical monitoring and because stability is dependent on size of the patterned features. To solve both problems, we obtained H NMR spectra of cured hydrogels which were enzymatically degraded.

Diastereoselective Synthesis of Highly Functionalized γ-Lactams via Ugi Reaction/Michael Addition.

The γ-lactam ring is a prominent feature in medicinal chemistry, and its synthesis has garnered significant interest due to its valuable properties. Among the γ-lactams, 2-oxopyrrolidine-3-carbonitrile derivatives stand out as versatile synthons that can be readily transformed into a variety of other functional groups. In this work, we successfully synthesized highly functionalized 3-cyano-2-pyrrolidinones with moderate to good overall yields using the Ugi reaction followed by intramolecular Michael addition.

Multi-site esterification: a tunable, reversible strategy to tailor therapeutic peptides for delivery.

Peptides are naturally potent and selective therapeutics with massive potential; however, low cell membrane permeability limits their clinical implementation, particularly for hydrophilic, anionic peptides with intracellular targets. To overcome this limitation, esterification of anionic carboxylic acids on therapeutic peptides can simultaneously increase hydrophobicity and net charge to facilitate cell internalization, whereafter installed esters can be cleaved hydrolytically to restore activity. To date, however, most esterified therapeutics contain either a single esterification site or multiple esters randomly incorporated on multiple sites.

A new ciprofibrate calcium salt with improved solubility and intrinsic dissolution rate.

Ciprofibrate (CIP) is an active pharmaceutical ingredient (API) classified as class II on the basis of biopharmaceutical classification system (BCS), what indicates that it has low solubility in aqueous solvents. The use of API salts has attracted attention due to their improvements in solubility, tolerability, higher rate and extent of absorption, and faster onset of the therapeutic effect. In this work, a new crystalline CIP monohydrated calcium salt (Ca(CIP).

Phenanthroline and phenyl carboxylate mixed ligand copper complexes in developing drugs to treat cancer.

The success of a classic inorganic coordination compound, Cisplatin, cis-[Pt(NH)Cl], as the first anticancer metallodrug started a field of research dedicated to discovering coordination compounds with antitumor activity, encompassing various metals. Among these, copper complexes have emerged as interesting candidates to develop drugs to treat cancer. In this work, mixed ligand complexes of Cu(II) with diimines (phenanthroline or 4-methylphenanthroline) and 3-(4-hydroxyphenyl)propanoate, phenylcarboxylate or phenylacetate were synthesized.

Synthesis of Cytotoxic Benzofurans and Ethers Derivatives of Paeonol.

Paeonol is a broadly studied natural product due to its many biological activities. Using a methodology previously employed by our research group, 11 derivatives of paeonol were synthesized (seven of them are unpublished compounds), including four ethers and seven benzofurans. Additionally, we determined the crystal structure of one of these ether derivatives (1 a) and of five benzofuran derivatives (2 a, 2 b, 2 c, 2 f and 2 g) by single crystal X-ray diffraction.

Measurement of covalent bond formation in light-curing hydrogels predicts physical stability under flow.

Photocrosslinking hydrogels are promising for tissue engineering and regenerative medicine, but challenges in reaction monitoring often leave their optimization subject to trial and error. The stability of crosslinked gels under fluid flow, as in the case of a microfluidic device, is particularly challenging to predict, both because of obstacles inherent to solid-state macromolecular analysis that prevent accurate chemical monitoring, and because stability is dependent on size of the patterned features. To solve both problems, we obtained H NMR spectra of cured hydrogels which were enzymatically degraded.

Crystal structure of 1-(1,3-benzo-thia-zol-2-yl)-3-(4-bromo-benzo-yl)thio-urea.

The chemical reaction of 4-bromo-benzoyl-chloride and 2-amino-thia-zole in the presence of potassium thio-cyanate yielded a white solid formulated as CHBrNOS, which consists of 4-bromo-benzamido and 2-benzo-thia-zolyl moieties connected by a thio-urea group. The 4-bromo-benzamido and 2-benzo-thia-zolyl moieties are in a conformtion (sometimes also called -trans due to the single bond) with respect to the N-C bond. The dihedral angle between the mean planes of the 4-bromo-phenyl and the 2-benzo-thia-zolyl units is 10.

Synthesis, characterization and structural analysis of complexes from 2,2':6',2''-terpyridine derivatives with transition metals.

The synthesis and structural characterization of three families of coordination complexes synthesized from 4'-phenyl-2,2':6',2''-terpyridine (8, Ph-TPY), 4'-(4-chlorophenyl)-2,2':6',2''-terpyridine (9, ClPh-TPY) and 4'-(4-methoxyphenyl)-2,2':6',2''-terpyridine (10, MeOPh-TPY) ligands with the divalent metals Co, Fe, Mn and Ni are reported. The compounds were synthesized from a 1:2 mixture of the metal and ligand, resulting in a series of complexes with the general formula [M(R-TPY)](ClO) (where M = Co, Fe, Mn and Ni, and R-TPY = Ph-TPY, ClPh-TPY and MeOPh-TPY). The general formula and structural and supramolecular features were determinated by single-crystal X-ray diffraction for bis(4'-phenyl-2,2':6',2''-terpyridine)nickel(II) bis(perchlorate), [Ni(CHN)](ClO) or [Ni(Ph-TPY)](ClO), bis[4'-(4-methoxyphenyl)-2,2':6',2''-terpyridine]manganese(II) bis(perchlorate), [Mn(CHNO)](ClO) or [Mn(MeOPh-TPY)](ClO), and bis(4'-phenyl-2,2':6',2''-terpyridine)manganese(II) bis(perchlorate), [Mn(CHN)](ClO) or [Mn(Ph-TPY)](ClO).

A new copper(II) complex containing long-chain aliphatic hydrazide and 1,10-phenanthroline upregulates ADP hydrolysis in triple-negative breast cancer cells.

Copper can be opportunely complexed to modulate oncogenic pathways, being a promising strategy for cancer treatment. Herein, three new copper(II) complexes containing long-chain aliphatic hydrazides and 1,10-phenanthroline (1,10-phen), namely, [Cu(octh)(1,10-phen)(HO)](NO)1, [Cu(dech)(1,10-phen)(HO)](NO)2 and [Cu(dodh)(1,10-phen)(HO)](NO).HO 3 (where octh = octanoic hydrazide, dech = decanoic hydrazide, dodh = dodecanoic hydrazide) were successfully prepared and characterized by several physical-chemical methods.

Unveiling a Strategy for Ring Opening of Epoxides: Synthesis of 2-Hydroxyindolinylidenes Using α-Ester Sulfoxonium Ylides.

The untapped potential of α-carbonyl sulfoxonium ylides in epoxide ring-opening reactions has been a notable gap in current research, with such reactivity predominantly associated with the highly reactive dimethylsulfoxonium methylide. This study introduces an innovative approach wherein an epoxide indole, formed from 2-hydroxyindoline-3-triethylammonium bromide, undergoes reaction with α-ester sulfoxonium ylides. The outcome is the efficient synthesis of a range of 2-hydroxyindolin-3-ylidenes, demonstrating favorable yields (41-81%) and / ratios from 4:1 to those of exclusive isomers.

Intensity and lifetime ratiometric luminescent thermometer based on a Tb(III) coordination polymer.

A three-dimensional terbium(III) coordination polymer of formula [Tb(bttb)(2,5-pzdc)] (1) [Hbttb = 1,2,4,5-tetrakis(4'-carboxyphenyl)benzene and H-2,5-pzdc = 2,5-pyrazinedicarboxylic acid] was obtained under hydrothermal conditions. The bttb tetraanion in 1 adopts the bridging and chelating-bridging pseudo-oxo coordination modes while the 2,5-pzdc dianion exhibits a rather unusual bis-bidentate bridging pseudo-oxo coordination mode, both ligands being responsible for the stiffness of the resulting 3D structure. Solid-state photoluminescent measurements illustrate that 1 exhibits remarkable green luminescence emission, the most intense band occurring in the region of 550 nm (D → F) with lifetimes at the millisecond scale.

Structural and Anticancer Studies of Methoxyflavone Derivative from A.St.-Hil. (Loganiaceae) from Brazilian Cerrado.

The Cerrado biome is the world's largest and most diversified tropical savanna. Despite its diversity, there remains a paucity of scientific discussion and evidence about the medicinal use of Cerrado plants. One of the greatest challenges is the complexity of secondary metabolites, such as flavonoids, present in those plants and their extraction, purification, and characterization, which involves a wide range of approaches, tools, and techniques.

Development of Copper Complexes with Diimines and Dipicolinate as Anticancer Cytotoxic Agents.

Coordination complexes may act as anticancer agents. Among others, the formation of the complex may facilitate the ligand uptake by the cell. Searching for new copper compounds with cytotoxic activity, the complex Cu-dipicolinate was studied as a neutral scaffold to form ternary complexes with diimines.

Crystalline and amorphous famotidine malate as pathways to prevent polymorphic transformation with improved dissolution.

Famotidine (FMT) is an orally administered histamine H2-receptor blocker with limited bioavailability since it exhibits low solubility and low permeability. In addition, the recent withdrawal of ranitidine from the market, makes famotidine an interesting candidate to obtain solid forms with improved pharmacokinetic performance. In this work, crystal engineering concepts and the co-amorphous formation strategy were applied to obtain two novel solids.

Tuning the Thermometric Features in 1D Luminescent Eu and Tb Coordination Polymers through Different Bridge Phosphine Oxide Ligands.

Tb and Eu systems have been investigated as ratiometric luminescent temperature probes in luminescent coordination polymers due to Tb → Eu energy transfer (ET). To help understand how ion-ion separation, chain conformation as well as excitation channel impact their thermometric properties, herein, [Eu(tfaa)(μ-L)Tb(tfaa)] one-dimensional (1D) coordination polymers (tfaa = trifluoroacetylacetonate, and L = [(diphenylphosphoryl)R](diphenyl)phosphine oxide, R = ethyl - dppeo - or butyl - dppbo) were synthesized. The short μ-dppeo bridge ligand leads to a more linear 1D polymeric chain, while the longer μ-dppbo bridge leads to tighter packed chains.

"Half-Sandwich" Ruthenium Complexes with Alizarin as Anticancer Agents: and Studies.

Upon exploration of the chemistry of the combination of ruthenium/arene with anthraquinone alizarin (L), three new complexes with the general formulas [Ru(L)Cl(η--cymene)] (), [Ru(L)(η--cymene)(PPh)]PF (), and [Ru(L)(η--cymene)(PEt)]PF () were synthesized and characterized using spectroscopic techniques (mass, IR, and 1D and 2D NMR), molar conductivity, elemental analysis, and X-ray diffraction. Complex exhibited fluorescence, such as free alizarin, while in and , the emission was probably quenched by monophosphines and the crystallographic data showed that hydrophobic interactions are predominant in intermolecular contacts. The cytotoxicity of the complexes was evaluated in the MDA-MB-231 (triple-negative breast cancer), MCF-7 (breast cancer), and A549 (lung) tumor cell lines and MCF-10A (breast) and MRC-5 (lung) nontumor cell lines.

It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities.

In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (-quinone/-quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929.

New Copper(II)-L-Dipeptide-Bathophenanthroline Complexes as Potential Anticancer Agents-Synthesis, Characterization and Cytotoxicity Studies-And Comparative DNA-Binding Study of Related Phen Complexes.

Searching for new copper compounds which may be useful as antitumor drugs, a series of new [Cu(L-dipeptide)(batho)] (batho:4,7-diphenyl-1,10-phenanthroline, L-dipeptide: Gly-Val, Gly-Phe, Ala-Gly, Ala-Ala, Ala-Phe, Phe-Ala, Phe-Val and Phe-Phe) complexes were synthesized and characterized. To interpret the experimental IR spectra, [Cu(ala-gly)(batho)] was modelled in the gas phase using DFT at the B3LYP/LANL2DZ level of theory and the calculated vibrational frequencies were analyzed. Solid-state characterization is in agreement with pentacoordinate complexes of the general formula [Cu(L-dipeptide)(batho)]·x solvent, similar to other [Cu(L-dipeptide)(diimine)] complexes.

Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene--acyl Hydrazones as Immunomodulatory Agents.

Immunomodulatory agents are widely used for the treatment of immune-mediated diseases, but the range of side effects of the available drugs makes necessary the search for new immunomodulatory drugs. Here, we investigated the immunomodulatory activity of new ferrocenyl-N-acyl hydrazones derivatives (SintMed(141−156). The evaluated N-acyl hydrazones did not show cytotoxicity at the tested concentrations, presenting CC50 values greater than 50 µM.

Structural, Theoretical Analysis, and Molecular Docking of Two Benzamide Isomers. Halogen Bonding and Its Role in the Diverse Ways of Coupling with Protein Residues.

The crystal structures of two methoxyphenylbenzamide isomers are described, (Ph2Br) and (Ph3Br), with the general formula CHBrNO. This structural study revealed the presence of N-H-O and C-H-O hydrogen bonds, Br-Br halogen bonds, C-H-π, and C-Br-π molecular contacts, showing in both compounds, a central C1-C7(O1)-N1(H1)-C8 amide segment, to be almost linear. The close proximity between the Br1 and O1 in Ph2Br showed that its interatomic distance was less than the sum of their VDW radii, generating an increase in the electrostatic potential in the O1 region, making possible the appearance of the so-called σ and π-holes on bromine.

Multifunctional Platform Based on a Copper(I) Complex and NaYF:Tm,Yb Upconverting Nanoparticles Immobilized into a Polystyrene Matrix: Downshifting and Upconversion Oxygen Sensing.

This work presents an innovative approach to obtain a multifunctional hybrid material operating via combined anti-Stokes (upconversion) and Stokes (downshifting) emissions for oxygen gas sensing and related functionalities. The material is based on a Cu(I) complex exhibiting thermally activated delayed fluorescence emission (TADF) and infrared-to-visible upconverting Tm/Yb-doped NaYF nanoparticles supported in a polystyrene (PS) matrix. Excitation of the hybrid material at 980 nm leads to efficient transfer of Tm emission in the ultraviolet/blue region to the Cu(I) complex and consequently intense green emission (560 nm) of the latter.

New ruthenium complexes containing salicylic acid and derivatives induce triple-negative tumor cell death via the intrinsic apoptotic pathway.

In this work we present the synthesis and characterization of six new ruthenium compounds with general formulae [Ru(L)(dppb)(bipy)]PF and [Ru(L)(dppe)]PF where L = salicylic acid (Sal), 4-aminosalicylic acid (AmSal) or 2,4-dihydroxybenzoic acid (DiSal), dppb = 1,4-bis(diphenylphosphino)butane, dppe = 1,2-bis(diphenylphosphino)ethane and bipy = 2,2'-bipyridine. The complexes were characterized by elemental analysis, molar conductivity, cyclic voltammetry, NMR, UV-vis and IR spectroscopies, and two by X-ray crystallography. The P{H} NMR spectra of the complexes with the general formula [Ru(L)(dppe)]PF showed that the phosphorus signals are solvent-dependent.