The successful clinical use of metal-based anticancer agents depends heavily on a detailed understanding of their absorption, distribution, metabolism, excretion, and toxicology (ADMET) profiles. This review evaluates the ADMET properties of anticancer complexes involving platinum, palladium, gold, ruthenium, copper, and zinc. Unlike traditional organic medicines, the ADMET processes of these compounds are often complex and nonlinear, due to their unique coordination chemistry, ligand-exchange kinetics, and dynamic speciation changes. The review highlights how structural differences in metal analogs influence their pharmacokinetics, systemic disposition, and distinct toxicity profiles. Ultimately, gaining a thorough understanding of these ADMET nuances is vital for designing next-generation metallodrugs with optimized tissue distribution, minimal systemic toxicity, and improved therapeutic effectiveness.

In this study, the kinetic and mechanistic studies of the substitution of chloride ligand of [(chloro)(2,6-bis(N-heterocyclic carbene)pyridine)Pd(II)]BF4 complexes, namely Pd1, Pd2, Pd3 and Pd4, by thiourea nucleophiles viz Tu, Dmtu and Tmtu were investigated. The rate of chloride substitution of dicyclometalated complexes was monitored in aqueous media containing 20 mM LiCl using stopped-flow spectrophotometry as a function of concentration and temperature under pseudo-first-order conditions. The kinetic data fitted to the pseudo-first-order rate law, kobs = k2[Nu]. The rate of chloride substitution decreased in the order Pd1 ˃ Pd2 ˃ Pd4 ˃ > Pd3. The reactivity of Pd1 was lower by two orders of magnitude compared to [Pd(terpy)Cl]+ (terpy = terpyridine). Both complexes have strong π-acceptor non-leaving ligands that promote efficient back bonding of charge into the aromatic bis(NHC) chelates of its non-leaving ligand. Contrastingly, the lutidine-bridged complexes, (Pd2-4) form 6-membered and non-aromatic bis(NHC) chelates which cause steric influence on either side of the square plane. Their substituents also impart additional steric effects and σ-inductive effects in the rings. The combined effect significantly lowers rates of substitution. Consequently, Pd3 was the least reactive. The substitution mechanism is associative since no evidence of a mechanistic change over to the dissociative substitution was observed, despite the complexes coordinated with tridentates with two cis-σ-bound carbon donors.

In this study, we synthesised and characterised three C<^>N<^>C pincer (N-heterocyclic carbene)-type tridentate ligands, namely, 2,6-bis[(3-methylimidazolium-1-yl)methyl]pyridine dibromide (L-1), 2,6-bis[(3-methylbenzimidazolium-1-yl)methyl]pyridine dibromide (L-2) and 2,6-bis[(3-butylimidazolium-1-yl)methyl]pyridine dibromide (L-3), and their corresponding six-membered chelates with Pt(II) to form PtL1-PtL3 complexes, namely, 2,6-bis[(3-methylimidazolium-1-yl)methyl]pyridinechloroplatinum(II) tetrafluoroborate (PtL1), 2,6-bis[(3-methylbenzimidazol-1-yl)methyl]pyridinechloroplatinum(II) tetrafluoroborate (PtL2) and 2,6-bis[(3-butylimidazol-1-yl)methyl]pyridinechloroplatinum(II) tetrafluoroborate (PtL3). Substitution kinetics using thiourea nucleophiles (tu, dmtu and tmtu), structural properties through theoretical DFT, biological interactions with DNA/BSA, electrochemical behaviors using cyclic voltammetry and docking simulations for Pt(II) C<^>N<^>C pincer complexes were investigated. The extended pi surface of benzimidazole (PtL2) caused sigma-donation in cis-Pt-C bonds, while N-butyl arms (PtL3) on the bis(3-methylimidazolium-1-yl)pyridine C<^>N<^>C pincer ligand had a steric influence on the labile ligand, leading to an increasing order of chloride substitution as follows: PtL3 < PtL2 < PtL1. The nucleophile's reactivity order is in accordance with its bulkiness, and the order is tu > dmtu > tmtu. Reactivity trends were justified by the trends in theoretical DFT data. Strong cis sigma-donor ligands prevent the co-coordination of the spectator ligand. Large negative entropy of activation (Delta S-#) and positive enthalpy of activation (Delta H-#) support a limiting associative substitution mechanism. Biological interactions of PtL1-PtL3 with CT-DNA and BSA complexes were confirmed using spectroscopic and cyclic voltammetry (CV) titrations, and the data obtained established moderate-to-strong binding affinities. Complexes bind to CT-DNA mainly via the groove mode and to a lesser extent via intercalation, whereas they insert into the upper protein cleft of BSA. Electrochemistry results also established the groove binding mode of interaction, and -Delta G values affirmed the binding process as spontaneous. Molecular docking simulations of PtL1-PtL3 with CT-DNA and BSA corroborated with groove binding being the main binding mode.

A series of 1,3-bis(2-arylimino)isoindoline Pd(II) complexes core viz.; Chlorido(1,3-bis(2-pyridylimino) isoindoline)palladium(II), Pd1, Chlorido(1,3-bis(4-methyl-2-pyridylimino)isoindoline)palladium(II), Pd2, Chlorido(1,3-bis(2-pyridylimino)benz(f)isoindoline)palladium(II), Pd3 and Chlorido(1,3-Bis(1isoquinolylimino)isoindoline)palladium(II), Pd4 were synthesized, appropriately characterized and the crystal structure of Pd2 elucidated. The kinetics and mechanism of the substitution of the chloride ligand with thiourea ligands, Tu, Dmtu and Tmtu, from the complexes were investigated under pseudo-first-order conditions. The analyses were performed using stopped-flow analyzer or UV-visible spectrophotometer. The reactions proceeded through two consecutive steps for most complexes with exception of Pd4 showing only a single step. The substitution rates followed the order: Pd1>Pd2>Pd3>Pd4 due to varying degrees of steric influences and sigma-/pi-donations caused by the methylation and benzannulation on the cis-/trans-positions of the pyridyl rings of the BPI. The quenching of the fluorescence of CT-DNA/EB by the Pd(II) complexes suggests static quenching mechanism. The simulated docking of the complexes onto CT-DNA suggests they bind mainly in the minor grooves of DNA. The UV-Visible absorption titrations and quenching of tryptophan (Trp) fluorescence of BSA by the complexes depict reasonable interactions which occur mainly in the hydrophobic domains of the former. The order of strength of the interaction of the complexes with DNA or BSA is consistent with the rates of substitution kinetics.

Alkali-activated municipal waste incineration fly ash (MWFA)-based geopolymers (GPA, GPB, and GPC) were synthesized under different sodium silicate to sodium hydroxide (SS/SH) ratios. The geopolymers were applied in the removal of endosulfan, a persistent and toxic chemical, from water. The adsorbents were characterized by XRD, SEM-EDX, and FTIR. Variation of SS/SH ratios resulted in morphologically distinguishable geopolymers with different compositions. The adsorption equilibrium data were best described by the Langmuir isotherm. The maximum adsorption capacities increased with an increase in SS/SH ratios in the order 1.87, 15.89, 16.97, and 20.01 mg/g for MWFA, GPA, GPB, and GPC, respectively. The kinetic data were best described by the pseudo-first-order model wherein the adsorption rate (k1) was independent of the SS/SH ratios and the geopolymer composition. The thermodynamic parameters, that is, enthalpy (∆H > 0), Gibbs free energy (∆G < 0), entropy (∆S > 0), and activation energy (Ea > 0), show that the processes were endothermic, spontaneous, physical (Ea and ∆H < 40 kJ/mol), and entropy-driven. Alkalination was beneficial since the geopolymers had a higher adsorption capacity (∼8–10 times) and affinity for endosulfan (∼30 times) than the precursor material (MWFA). The adsorption mechanism entailed electrostatic interactions and hydrogen bonding. The MWFA-based geopolymers are, therefore, potential alternative low-cost adsorbents for the removal of endosulfan from water and a strategy for the valorization of MWFA.

Substitution kinetics of the aqua ligands in four binuclear ruthenium(II) para-cymene complexes with different alpha,alpha'-diimine bridging ligands [2-pyridylaldazine (Ru-1), p-phenylenebis(picoline)aldimine (Ru-2), p-biphenylenebis(picoline)aldimine (Ru-3) and p-xylenebis(picoline)aldimine (Ru-4)] was investigated as a function of nucleophile concentration and temperature under pseudo-first order conditions using thiourea nucleophiles. The rates of the simultaneous substitution of the aqua ligands decreased in the order: Ru-1 > Ru-4 > Ru-3 > Ru-2. The reactivity of the complexes is controlled by the inherent electronic and steric contributions of the bridging ligand. The strong T-acceptor bridging ligand is responsible for the high reactivity observed in Ru-1 compared to the rest of the complexes. From Ru-2 to Ru-4, the reactivity increases with decrease in steric congestion around the metal centres. The cage effect plays a role in the enhanced reactivity of Ru-4 compared to Ru-3 and Ru-2. Reactivity trends are excellently supported by computational results. All the complexes showed a stepwise deprotonation of the coordinated aqua ligands except Ru-4 and the pKa values increased from Ru-1 to Ru-4 due to progressive increase in sigma-donicity of the spacers. The activation parameters (Delta H-not equal > 0, Delta S-not equal < 0) obtained for all the complexes support an associative mechanism of activation.

The rates of substitution of chloro ligands from a series of ruthenium(II) complexes, [Ru(kappa(3)-L)(PPh3)Cl-2] (L = 2,2 ':6 ',2 ''-terpyridine, 1; 4 '-(4-methylphenyl)-2,2 ':6 ',2 ''-terpyridine, 2; 4,4 ' 4 ''-tri-tert-butyl-2,2 ':6 ',2 ''-terpyridine, 3; 4 '-(4-chlorophenyl)-2,2 ':6 ',2 ''-terpyridine, 4; 4-chloro-2,2 ':6 ',2 ''-terpyridine, 5 and 2,6-bis(2-pyrazolyl)pyridine, 6), by thiourea nucleophiles was investigated under pseudo-first-order conditions in methanol as a function of nucleophile concentration and temperature. The chloro ligands were substituted in two steps and the reactivity trend was 4 > 5 > 2 > 1 > 6. Complexes 2 and 3 having donor substituents on the 2,2 ':6 ',2 ''-terpyridine backbone experience a trans-effect making them more reactive than 1. Complexes 4 and 5 are more reactive than 1 due to enhanced pi-back-bonding brought about by electron-withdrawing substituents on their 2,2 ':6 ',2 ''-terpyridine backbones. The reactivity of 4 is higher than 5 due to greater electron acceptor-ability of the chlorophenyl substituent than the chloro substituent in 5. The 2,6-bis(pyrazolyl)pyridine ligand in 6 retards the reactivity of the complex compared to 1 due to the cis-donor effect of the pyrazole. The reactivity of the complexes is associative for all nucleophiles in step one and only thiourea in step two. The substitution reactions proceed by a steady changeover from an associative interchange mechanism (I (a)) to a dissociative interchange (I (d)) mechanism on increasing steric hindrance.

Four [(N"N"N)(PdCl)-Cl-(II)]+ complexes [chloride-(2,2 ':6 ',2 ''-terpyridine)Pd-(II)]Cl (PdL1), [chlorido(2,6-bis(N-pyrazol-2-yl)pyridine)Pd(II)]Cl (PdL2), [chlorido(2,6-bis(3,5-dimethyl-N-pyrazol-2-yl)pyridine)Pd(II)]Cl (PdL3) and [chlorido(2,6-bis(3,5-dimethyl-N-pyrazol-2-ylmethyl)pyridine)Pd(II)]BF4 (PdL4) were synthesized and characterized. The rates of substitution of these Pd(II) complexes with thiourea nucleophiles viz; thiourea (Tu), N,N '-dimethylthiourea (Dmtu) and N,N,N ',N '-tetramethylthiourea (Tmtu) was investigated under pseudo first order conditions as a function of nucleophile concentration [Nu] and temperature using the stopped-flow technique. The observed rate constants vary linearly with [Nu]; k(obs) = k(2)[Nu] and decreased in the order: PdL1 > PdL2 > PdL3 >> PdL4. The lower pi-acceptability of the cis-coordinated N-pyrazol-2-yl groups (which coordinates via pyrazollic-N pi-donor atoms) of the PdL2-4 significantly decelerates the reactivity relative to PdL1. Furthermore, the six-membered chelates having methylene bridge in PdL4 do not allow pi-extension in the ligand and introduces steric hindrance further lowering the reactivity. Trends in DFT calculated data supported the observed reactivity trend. Spectrophotometric titration data of complexes with calf thymus DNA (CT-DNA) and viscosity measurements of the resultant mixtures suggested that associative interactions occur between the complexes and CT-DNA, likely through groove binding with high binding constants (K-b = 10(4) M-1). In vitro MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxic activity data showed that PdL1 was the most potent complex against MCF7 breast cancer cells; its IC50 value is lower than that of cisplatin. The results demonstrate how modification of a spectator ligand can be used to slow down the reactivity of Pd(II) complexes. This is of special importance in controlling drug toxicity in both pharmaceutical and biomedical applications.

The rate and mechanism of chloride substitution from Pd(II) complexes, chlorobis-(2-pyridylmethyl)aminepalladium(II), 1, chloro-8-[(2-pyridylmethyl)amino]quinolinepalladium(II), 2, chloro-N-(2-pyridinylmethylene)-8-quinolinaminepalladium(II), 3, and chlorobis(8-quinolinyl)aminepalladium(II), 4, are reported. The labile chloride was substituted from the complexes by thiourea nucleophiles viz, thiourea (Tu), N,N '-dimethylthiourea (Dmtu) and N,N,N ',N '-tetramethylthiourea (Tmtu). The reactions were monitored under pseudo-first-order conditions in methanol using stopped-flow spectrophotometry as a function of concentration and temperature. All the reactions obeyed the rate law k(obs) = k(2)[Nu] following the order 1 > 3 > 2 > 4 with 4 exhibiting the slowest rate of substitution due to the stronger sigma-donor effect of 8-quinolyl moiety of the coordinated ligand, which makes the Pd center more electron-rich. This slows the nucleophilic attack by the nucleophiles. The values of the thermodynamic parameters (Delta H-# and Delta S-#) support an associative substitution mechanism. The trends in the DFT calculated data support the experimentally observed order of the reactivity of the complexes. [GRAPHICS] .

Carbofuran (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate) has been used within the Nzoia River Basin (NRB), especially in Bunyala Rice Irrigation Schemes, in Kenya for the control of pests. In this study, the capacity of native bacteria to degrade carbofuran in soils from NRB was investigated. A gram positive, rod-shaped bacteria capable of degrading carbofuran was isolated through liquid cultures with carbofuran as the only carbon and nitrogen source. The isolate degraded 98% of 100-μg mL−1 carbofuran within 10 days with the formation of carbofuran phenol as the only detectable metabolite. The degradation of carbofuran was followed by measuring its residues in liquid cultures using high performance liquid chromatography (HPLC). Physical and morphological characteristics as well as molecular characterization confirmed the bacterial isolate to be a member of Bacillus species. The results indicate that this strain of Bacillus sp. could be considered as Bacillus cereus or Bacillus thuringiensis with a bootstrap value of 100% similar to the 16S rRNA gene sequences. The biodegradation capability of the native strains in this study indicates that they have great potential for application in bioremediation of carbofuran-contaminated soil sites.