Phenoxy Moiety Research Articles

3-[2-(Oxiran-2-yl)ethyl]-1-{4-[(2-oxiran-2-yl)ethoxy]benzyl}imidazolium bis(Trifluoromethane)sulfonimide

The synthesis of 3-[2-(oxiran-2-yl)ethyl]-1-{4-[(2-oxiran-2-yl)ethoxy]benzyl}imidazolium bis(trifluoromethane)sulfonimide was achieved in seven steps with an overall yield of 63%. This ionic liquid monomer is based on an imidazolium core containing a phenoxy moiety and aliphatic chains with a reactive epoxide at both ends. This imidazolium was obtained by an efficient, reproducible, and scalable synthesis from inexpensive reagents. In the last step, a powerful oxidative agent was successfully used to generate two epoxy functions with only acetone as a byproduct. The monomer structure and intermediates were analyzed by NMR experiments, infrared, and mass spectra. In addition, the thermal properties of the diepoxide were evaluated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC).

Tricyclic xanthine derivatives containing a basic substituent: adenosine receptor affinity and drug-related properties.

A library of 27 novel amide derivatives of annelated xanthines was designed and synthesized. The new compounds represent 1,3-dipropyl- and 1,3-dibutyl-pyrimido[2,1-f]purinedione-9-ethylphenoxy derivatives including a CH2CONH linker between the (CH2)2-amino group and the phenoxy moiety. A synthetic strategy to obtain the final products was developed involving solvent-free microwave irradiation. The new compounds were evaluated for their adenosine receptor (AR) affinities. The most potent derivatives contained a terminal tertiary amino function. Compounds with nanomolar AR affinities and at the same time high water-solubility were obtained (A1 (Ki = 24-605 nM), A2A (Ki = 242-1250 nM), A2B (Ki = 66-911 nM) and A3 (Ki = 155-1000 nM)). 2-(4-(2-(1,3-Dibutyl-2,4-dioxo-1,2,3,4,7,8-hexahydropyrimido[2,1-f]purin-9(6H)-yl)ethyl)phenoxy)-N-(3-(diethylamino)propyl)acetamide (27) and the corresponding N-(2-(pyrrolidin-1-yl)ethyl)acetamide (36) were found to be the most potent antagonists of the present series. While 27 showed CYP inhibition and moderate metabolic stability, 36 was found to possess suitable properties for in vivo applications. In an attempt to explain the affinity data for the synthesized compounds, molecular modeling and docking studies were performed using homology models of A1 and A2A adenosine receptors. The potent compound 36 was used as an example for discussion of the possible ligand-protein interactions. Moreover, the compounds showed high water-solubility indicating that the approach of introducing a basic side chain was successful for the class of generally poorly soluble AR antagonists.

Functionalized 2,1-benzothiazine 2,2-dioxides as new inhibitors of Dengue NS5 RNA-dependent RNA polymerase

Over recent years, many RNA viruses have been “re-discovered”, including life-threatening flaviviruses, such as Dengue, Zika, and several encephalitis viruses. Since no specific inhibitors are currently available to treat these infections, there is a pressing need for new therapeutics. Among the flaviviral proteins, NS5 RNA-dependent RNA polymerase (RdRp) represents a validated target being essential for viral replication and it has no human analog. To date, few NS5 RdRp inhibitor chemotypes have been reported and no inhibitors are currently in clinical development. In this context, after an in vitro screening against Dengue 3 NS5 RdRp of our in-house HCV NS5B inhibitors focused library, we found that 2,1-benzothiazine 2,2-dioxides are promising non-nucleoside inhibitors of flaviviral RdRp with compounds 8 and 10 showing IC50 of 0.6 and 0.9 μM, respectively. Preliminary structure-activity relationships indicated a key role for the C-4 benzoyl group and the importance of a properly functionalized C-6 phenoxy moiety to modulate potency. Compound 8 acts as non-competitive inhibitor and its proposed pose in the so-called N pocket of the RdRp thumb domain allowed to explain the key contribution of the benzoyl and the phenoxy moieties for the ligand binding.

Synthesis of New Arylidene 2,5-Diketopiperazines and Evaluation of their Anti-Acetylcholinesterase, Anti-xanthine Oxidase, Anti-diabetic and Cytotoxic Activities

2,5-Diketopiperazine derivatives are considered to be an important classe of cyclic peptides due to their wide range of biological activities. Synthesis of a new series of protected 2,5-diketopiperazine derivatives and evaluation of their in vitro biological activities. A series of new mono-protected arylidene 2,5-diketopiperazine derivatives 3a-p have been prepared via Claisen-Schmidt condensation of the N,N-diacetyl-diketopiperazine 1 with a series of substituted arylaldehydes. All prepared compounds were characterized by 1D and 2D 1H/13C NMR and ESI-HRMS, and screened for their in vitro acetylcholenesterase, xanthine oxidase and α-amylase inhibition and cytotoxic (HCT-116, MCF-7 and OVCAR-3) activity. Among these compounds, the greatest activity against the α-amylase enzyme (percentage of inhibition (PI)=57.8±1.9%) was obtained for compound 3f bearing a phenoxy moiety. Moreover, the results demonstrated that some arylidene 2,5-diketopiperazines 3 exhibited significant cytotoxic activity against the three cell lines used. The compound 3g (4-PhCH2O.Ph) was found to be the most cytotoxic against the HCT-116, MCF-7 and OVCAR-3 cell lines (PI=83.2±2.4, 89.6±4.9 and 74.4±5.2%, respectively) followed by 3m (2-Br-5-F.Ph) then 3j (4-C2H5-3-NO2.Ph) which displayed a good cytotoxic potential against OVCAR-3 (PI=77.0±2.1 and 71.4±0.9%, respectively). A series of sixteen new arylidene diketopiperazines 3a-p were synthesized via Claisen-Schmidt condensation. Most of the piperazines 3a-p exhibited a good cytotoxic and antidiabetic effects.

Lyotropic liquid crystalline phthalocyanines containing 4-((S)-3,7-dimethyloctyloxy)phenoxy moieties

The novel metal free phthalocyanine and its copper complex which are octa-substituted at the peripheral positions with 4-(([Formula: see text]-3,7-dimethlyoctyloxy)phenoxy moieties were synthesized and characterized by FT-IR, 1H NMR and mass spectroscopy. Their mesomorphic properties were studied by polarizing optical microscopy. The spectroscopic properties and aggregation behaviors of the novel phthalocyanines were also investigated by UV-vis spectroscopy in different solvents with same concentration as well as in a wide range of concentrations of chloroform. Both compounds with chloroform and [Formula: see text]-dodecane clearly show the lyotropic columnar mesophase in a wide temperature range whereas thermotropic liquid crystalline behavior for both compounds is not observed. Both of these novel compounds show no aggregation in toluene, tetrahydrofuran, dichloromethane and chloroform.

The replacement of the 2-methoxy substituent of N-((6,6-diphenyl-1,4-dioxan-2-yl)methyl)-2-(2-methoxyphenoxy)ethan-1-amine improves the selectivity for 5-HT1A receptor over α1-adrenoceptor and D2-like receptor subtypes

N-((6,6-diphenyl-1,4-dioxan-2-yl)methyl)-2-(2-methoxyphenoxy)ethan-1-amine (3) is a potent 5-HT1A receptor and α1d-adrenoceptor (α1d-AR) ligand. Analogues 5–10 were rationally designed and prepared to evaluate whether electronic and/or lipophilic properties of substituents in the ortho position of its phenoxy moiety exert any favorable effects on the affinity/activity at 5-HT1A receptor and improve selectivity over α1-ARs. To rationalize the experimental observations and derive information about receptor-ligand interactions of the reported ligands, docking studies, using 5-HT1A and α1d-AR models generated by homology techniques, and a retrospective computational study were performed. The results highlighted that proper substituents in position 2 of the phenoxy moiety of 3 selectively address the ligands toward 5-HT1A receptor with respect to α1-ARs and D2-like receptor subtypes. Methoxymethylenoxy derivative 9 showed the best 5-HT1A selectivity profile and the highest potency at 5-HT1A receptor, behaving as a partial agonist. Finally, 9, tested in light/dark exploration test in mice, significantly reduced anxiety-linked behaviors. Therefore, it may be considered a lead for the design of partial agonists potentially useful in the treatment of disorders in which 5-HT1A receptor is involved.

Looking for new antiplasmodial quinazolines: DMAP-catalyzed synthesis of 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines and their in vitro evaluation toward Plasmodium falciparum

A DMAP catalyzed synthesis of new 4-benzyloxy- and 4-aryloxy-2-trichloromethylquinazolines was studied, in a view to react 4-chloroquinazolines with poorly nucleophilic alcohols such as benzylic alcohols, via a simple and cheap SNAr reaction approach. A fast (1 h) general operating procedure, affording good reaction yields, was achieved under microwave irradiation. Thus, a series of 35 molecules was obtained and evaluated in vitro on the K1 multi-resistant Plasmodium falciparum strain, in parallel with a cytotoxicity assessment on the human HepG2 cell line. 5 hit-molecules were identified, presenting both promising antiplasmodial activity (1.5 μM < IC50 < 2 μM) and low cytotoxicities (25 μM < CC50 < 45 μM). Apart for 2 molecules, the global series displayed a satisfying solubility in the aqueous biological media. Structure-activity relationships showed that the molecules presenting a benzyloxy moiety were less cytotoxic than the ones bearing a phenoxy moiety at position 4 of the quinazoline ring. It also appeared that the introduction of a heteroaryl moiety afforded inactive compounds. Finally, the most active and selective molecules (Selectivity Index = 22–27) were the ones presenting either an unsubstituted benzyloxy group or a phenoxy group, this last bearing a p-bromo or an o-acetyl substituent.

Platinum(ii) cyclometallates featuring broad emission bands and their applications in color-tunable OLEDs and high color-rendering WOLEDs

Two new phosphorescent platinum(ii) cyclometallates with flexible phenoxy moieties were prepared whose broad excimeric emissive states in the solid state allow the fabrication of high color-rendering two-emitter WOLEDs.

Phenoxy-Linked Mesoionic Triazol-5-ylidenes as Platforms for Multinuclear Transition Metal Complexes

The preparation and full characterization of a variety of mono- ([L1-H]), di- ([L2-H2], [L2A-H2]), and tri- ([L3-H3]) 1,2,3-triazolium salts constructed form “clicked” hydroxybenzene derivatives are reported. Deprotonation with potassium hexamethyldisilazide, followed by in situ metalation, allowed for the synthesis of a series of mono- (L1·[M]), di- (L2·[M]2, L2·[M]2), and trinuclear (L3·[M]3) group 9–11 (M = [Rh(CO)2Cl], [Pd(allyl)Cl], and [AuCl]) triazol-5-ylidene metal complexes. In solution, all metal complexes feature symmetrical patterns displaying C2 and C3 fold axes when supported by di- and tritriazol-5-ylidene ligands. The vibration frequencies of Ln·[Rh(CO)2Cl]n (n = 1–3) complexes indicate that the electron-donor properties of the new ligands are comparable to those for previously reported MIC complexes and superior to classical NHCs. Prompting coordination of the vicinal phenoxy group to the metal centers proved unsuccessful after treatment of the Ln·[Rh(CO)2Cl]n and Ln·[Pd(allyl)Cl]n (n = 1–3) precursors with AgBF4; the expected chelated cationic complexes were highly unstable, indicating a weak or no coordination availability through the oxygen atom. Crystal structures of the complexes L1·[AuI] and L2A·[Pd(allyl)I]2 illustrated the metal center geometrical environment and confirmed the lack of coordination through the phenoxy moiety of the ligand. Preliminary catalytic trials established the enhanced performance of di- and trimetallic palladium complexes in cross-coupling reactions and the intramolecular cyclization of enynes catalyzed by gold complexes.

Thermotropic Behavior of Syndiotactic Polymethylenes with ω-[4-(trans-4-Pentylcyclohexyl)phenoxy]alkyloxycarbonyl Side Chains

A series of syndiotatic P5CPn polymethylenes was prepared with 4-(trans-4-pentylcyclohexyl)phenoxy moieties linked to each backbone carbon atom via an alkyloxycarbonyl spacer and with even numbers of alkyl carbons n ranging from 2 to 14, and their thermotropic behaviors were investigated. The P5CPn, except P5CP2, formed smectic phases in which the rod-like polymethylene backbones were arranged in rectangular lattices, and the side-chain mesogens were aggregated into layers parallel to the shorter sides of the rectangular lattices. The packing of the mesogens changed with decreasing temperature from smectic C-like to smectic I-like (SmI-like) for n = 4–8 and from smectic A-like to SmI-like for n = 10–14. In the SmI-like phases, each mesogen along the main-chain axis was connected to every sixth backbone carbon atom, revealing a correlation between the packing of the mesogens and the main-chain conformation of a 3/2 helix. Conversely, P5CP2 formed a smectic phase with the main chains arranged in rows and with the mesogens barely aggregated into layers due to the short spacers.

Fractional Extraction and Biodepolymerization of Shengli Lignite

Shengli lignite (SL) was sequentially extracted with aqueous NaOH solution, n-hexane, dichloromethane, an azeotropic mixture of benzene and ethanol, and acetone to obtain extracts 1–5 (E1–E5). Each extract was analyzed using a gas chromatograph/mass spectrometer (GC/MS) and then depolymerized by an isolated fungus. Most of E1 cannot be detected by GC/MS perhaps because of strong polarity, and E1 is recognized as humic acids. E2–E5 consist of normal alkanes, arenes, alkanols, phenols, ketones, carboxylic acids, esters, and organonitrogens according to GC/MS analysis. The biodepolymerization (BDP) of E1 is much easier than that of other extracts. According to GC/MS analysis, both 2,4-xylenzo[h]quinoline and methyl 3-(acetoxymethyl)biphenylene-2-carboxylate disappeared, while 3-(1-ethoxyethoxy)butanal, propane-1,2-diyl diformate, 3-phenylbutan-2-ol, and 2-methyl-7-phenyl-1H-indole were produced from the BDP of E1. In comparison to E1 before BDP, the phenoxy moiety in E1 after BDP was significantly reduced ac...

Looking for new antileishmanial derivatives in 8-nitroquinolin-2(1H)-one series.

From a recently identified antileishmanial pharmacophore, a structure-activity relationship study was conducted by introducing various aminated, phenoxy or thiophenoxy moieties at position 4 of the 8-nitroquinolin-2(1H)-one scaffold, using SNAr reactions. Thus a series of 47 derivatives was synthesized and evaluated invitro on the promastigote stage of Leishmania donovani. In parallel, the cytotoxicity of the active molecules was tested on the human HepG2 cell line. The results we obtained showed that the introduction of a substituent at position 4 of the antileishmanial pharmacophore can either lead to inactive or active derivatives, depending on the nature of the substituent. Aminated moieties appear as very unfavorable toward antileishmanial activity, while phenoxy or thiophenoxy moieties were shown to maintain the invitro antileishmanial profile, especially when the phenyl ring of these moieties was substituted at the para or ortho position by ahalogen atom (except fluorine), a trifluoromethyl group or a methyl group. Most of these derivatives showed a lack of solubility in the culture media which hindered the invitro determination of both their cytotoxicity and activity against the intracellular amastigoste stage of L.donovani.

Direct Chain End Functionalization of Living Polyisobutylene Using Phenoxyalkyl (Meth)acrylates.

Phenoxyalkyl acrylates and methacrylates were studied as quenching (capping) agents for living carbocationic polymerization of isobutylene (IB) at -70 °C in 40/60 (v/v) hexane/methyl chloride, catalyzed by TiCl4. Quenching reactions were carried out by reactivation by TiCl4 of preformed difunctional tert-chloride-terminated polyisobutylene (PIB) or by a one-step method in which IB polymerization and quenching were conducted sequentially in the same reactor. Chain-end concentrations ranged from 0.02 to 0.1 M, and quenchers were used at concentrations of 1.5-2.5 times the chain ends. The phenoxyalkyl (meth)acrylates were synthesized by reaction of (meth)acryloyl chloride with the corresponding phenoxyalkanol; alkylene tethers from two to eight carbons were examined. Quenched polymers were characterized by 1H and 13C NMR, MALDI-TOF mass spectrometry, and size exclusion chromatography (SEC). Alkylation was observed to occur exclusively at the para position of the phenoxy moiety, and SEC showed no coupling or molecular weight degradation as a result of quenching. For short tethers of two or three carbons, quenching was slow and incomplete due to competing loss of living chain ends presumably by carbocation rearrangement. For tethers of four, six, or eight carbons, quenching was much faster and yielded quantitative (meth)acrylate chain-end functionality (number-average functionality ≥1.98 by 1H NMR). MALDI-TOF-MS results were consistent with the expected end group structures. The carbonyl group of the quencher consumes one equivalent of Lewis acid in formation of a 1:1 complex; thus, the highest rate of quenching at a given Lewis acid concentration is achieved by using only a modest excess of quencher relative to living chain ends.

Novel shikonin derivatives targeting tubulin as anticancer agents.

In this study, we report the identification of a new shikonin-phenoxyacetic acid derivative, as an inhibitor of tubulin. A series of compounds were prepared; among them, compound 16 [(R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 2-(4- phenoxyphenyl) acetate] potently inhibited the function of microtubules, inducing cell growth inhibition, apoptosis of cancer cell lines in a concentration and time-dependent manner. Molecular docking involving 16 at the vinblastine binding site of tubulin indicated that a phenoxy moiety interacted with tubulin via hydrogen bonding with asparaginate (Asn) and tyrosine (Tyr). Analysis of microtubules with confocal microscopy demonstrated that 16 altered the microtubule architecture and exhibited a significant reduction in microtubule density. Cell cycle assay further proved that HepG2 cells were blocked in G2/M phase. Our study provides a new, promising compound for the development of tubulin inhibitors by proposing a new target for the anticancer activity of shikonin.

Nowe pochodne benzimidazolu i benzotiazolu z ugrupowaniem fenoksylowym o aktywności herbicydowej

A series of new substituted benzimidazole and benzothiazole containing phenoxy moiety and halogenomethylsulfonyl groups were synthesized. Biological activity of synthesized compounds was evaluated in screening tests. The (R) enantiomers of benzothiazole derivatives containing difluoromethylsulfonyl groups in the benzene ring and phenoxy moiety in the imidazole sceleton exhibited good herbicidal activity. Zsyntezowano nowe pochodne benzoimidazolu i benzotiazolu zawierające w pozycji 2 ugrupowania fenoksyetylowe, a w pierścieniu benzenowym grupy fluorometylosulfonylowe. Oceniono aktywność biologiczną związków w doświadczeniach skryningowych. Najwyższą aktywność chwastobójczą wykazywały enancjomery (R) pochodnych benzotiazolu zawierające w pierścieniu benzenowym ugrupowanie difluorometylosulfonylowe, a w pierścieniu imidazolowym grupy fenoksyetylowe.

Structural Influence of C8-Phenoxy-Guanine in the NarI Recognition DNA Sequence

Phenoxyl radicals can covalently attach to the C8 site of 2'-deoxyguanosine (dG) to generate oxygen-linked biaryl ether C8-dG adducts. To assess the structural impact of an O-linked C8-dG adduct in duplex DNA, C8-phenoxy-G ((PhO)G) and C8-4-fluorophenoxy-G ((4FPhO)G) were incorporated into the G(3) position of the 12-mer NarI recognition sequence (5'-CTCGGCXCCATC, where X = G, (PhO)G, or (4FPhO)G) using solid-phase DNA synthesis with O-linked C8-dG phosphoramidites. The modified strands were hybridized to six different complementary strands that include regular base pairing to C [NarI'(C)], mismatches with G, A, T [NarI'(N)], and an abasic site [NarI'(THF)], and a 10-mer sequence to model a -2 deletion duplex [NarI'(-2)]. All duplex structures were characterized using UV-vis thermal melting temperature analysis, and in each instance, the O-linked C8-phenoxy-G adducts were found to destabilize the duplex relative to the unmodified controls. The most stable duplex structures match the O-linked C8-dG adduct against C and a G mismatch, which are comparable in terms of stability. These duplexes were further characterized using circular dichroism, dynamic (19)F nuclear magnetic resonance experiments, and molecular dynamics simulations. On the basis of these findings, (PhO)dG adopts the B conformation opposite C, with the phenoxy moiety residing in the solvent-exposed major groove. However, opposite the G mismatch, (PhO)dG adopts a "W-type" wedge conformation with the phenoxy group residing in the minor groove. These studies predict that the O-linked C8-dG lesion (PhO)G will have a weak mutagenic effect, as determined for the corresponding single-ringed nitrogen-linked C8-dG adduct derived from aniline.

8-Alkoxy- and 8-Aryloxy-BODIPYs: Straightforward Fluorescent Tagging of Alcohols and Phenols

We demonstrate herein that both alcohols and phenols can be tagged with a BODIPY (borondipyrromethene) moiety to yield highly fluorescent products. Thus, 8-(methylthio)-BODIPY (1) undergoes an S(N)Ar-type reaction with a host of alcohols and phenols in the presence of a base and a Cu(I) additive. The BODIPY dyes bearing alkoxy or nonfunctionalized phenoxy moieties are characterized by a highly efficient fluorescence emission, regardless of the media, in the blue-green part of the visible region. Complementary to this, the presence of electron-donor groups at the aryl ring leads to an intramolecular charge-transfer process, which quenches the fluorescence mainly in polar media. In addition to simple alcohols and phenols, four natural products (eugenol, menthol, cholesterol, and estrone) were labeled in a simple fashion. X-ray structures of the cholesterol and estrone derivatives are discussed. In fact, the BODIPY bearing cholesterol stands out as a bright fluorescence biological marker.

Titanyl phthalocyanines: Electrochemical and spectroelectrochemical characterizations and electrochemical metal ion sensor applications of Langmuir films

Electrochemical and spectroelectrochemical characterizations of titanyl phthalocyanines, which were peripheral (α-TiOPc) and nonperipheral (β-TiOPc) tetra and octa substituted (octa-TiOPc) with 3,4-(methylendioxy)-phenoxy moieties were performed to determine their possible applications in different electrochemical technologies. Voltammetric and in situ spectroelectrochemical measurements illustrate that position and number of 3,4-(methylendioxy)-phenoxy substituents affect the redox behavior of the complexes. While α-TiOPc gives up to four reduction processes, β-TiOPc and octa-TiOPc gives up to three reduction processes. While octa-TiOPc gives metal–metal–ring–ring reductions, α-TiOPc and β-TiOPc complexes give metal–ring–ring–metal reduction mechanism. Solvent of the media also alter the electrochemical behavior of the complexes. In situ electrocolorimetric measurements shows distinct color differences among the electrogenerated anionic and cationic redox species, which indicates their possible applications in display technologies. Multiple and reversible, diffusion controlled and multi-electron redox reaction indicate possible usage of the complexes especially in electrosensing applications. The complexes sense Ag+ and Pd2+ ions in the solution and in the solid states.

Synthesis, structure, and solid-state phosphorescence of heteroleptic platinum(II) complexes bearing iminophenyl and iminophenoxy ligands

A series of heteroleptic platinum(II) complexes 1 bearing iminophenyl and iminophenoxy ligands have been synthesized and characterized using NMR, IR, and emission spectroscopies, mass spectrometry, and single crystal X-ray diffraction. The complexes exhibit intense phosphorescent emission with an absolute quantum efficiency (Φ298K) up to 0.29 in the crystalline state. Chromogenic control of solid-state emission over a range of 99 nm can be performed simply by introducing methoxy (MeO) groups at different positions on the aromatic rings. Hypsochromic and bathochromic shifts from the orange 1a crystal are observed with 4-/11-MeO (para-position of the imine moieties on the phenyl and phenoxy ligands; yellow emission) and 5-/12-MeO (para-position of the phenyl and phenoxy moieties; reddish orange and red emission) substitution, respectively. Time-dependent density functional theory (TD-DFT) calculations (B3LYP/6-31G*, LanL2DZ) indicated that the chromatic variation can be ascribed to the position-specific influence of the substituents on the HOMO and LUMO levels. The solid-state emission and heat-resistance are discussed based on the molecular packing of the crystals.

{Phenoxy-imine}aluminum versus -indium Complexes for the Immortal ROP of Lactide: Different Stereocontrol, Different Mechanisms

A series of dialkylaluminum and -indium {ONR}MR′2 complexes (M = Al, R′ = Me; M = In, R′ = Me, CH2SiMe3) stabilized by a phenoxy-imine {ONR}− ligand platform, with variable R-imino substituents and functionalized by a bulky o-SiPh3 in the phenoxy moiety, has been prepared and structurally characterized in solution and in the solid state. {ONR}AlMe2 complexes reacted with alcohols, in particular with alkyl (S)-H-lactate, to generate the corresponding {ONR}Al(OR)2 compounds. On the other hand, the indium complexes {ONR}InR′2 proved largely inert toward alcohols. When they were combined with an alcohol (iPrOH, BnOH), the {ONR}AlMe2 complexes promoted the living (immortal) ring-opening polymerization ((i)ROP) of racemic lactide (rac-LA) with a good control over the molecular weights and various microstructures, dependent on the R-imino substituent. Complexes having benzyl-type imino substituents enabled the achievement of significant isotacticity (Pm up to 0.80), following grossly the bulkiness of the aryl moiety. The analogous {ONR}InR′2 proved similarly active for the (i)ROP of rac-LA in presence of an external alcohol, but the polymerizations were less controlled and none of the complexes induced stereoselectivity, except one (3a,Pm = 0.70). Kinetic studies revealed different rate laws, with an apparent zero-order dependence on monomer for the aluminum system 1m/iPrOH and a first-order dependence on monomer for the analogous indium system 3m/iPrOH. On the basis of the stoichiometric reactivity of model compounds, two different operative ROP mechanisms are suggested, depending on the nature of the metal center: Al-based complexes proceed through coordination–insertion, while In-based complexes are proposed to operate through an activated monomer mechanism.