Biological Activity Of Ligand Research Articles

Synthesis of metal(II) acetate complexes with a heterocyclic azo dye ligand: Characterization, geometrical molecular structures, antioxidant, biological activities, DNA binding and molecular docking studies

A series of Cu(II), Co(II), Ni(II), Mn(II), and UO2(II) complexes have been prepared from the ligand 4-(2’,4’-dihydroxybenzaldehyde phenylazo)antipyrine (H2L). FT-IR spectra demonstrated that the ligand under investigation behaves as a bi-and tridentate centre ligand through the phenolic oxygen of aldehydic, azo nitrogen atoms and carbonyl oxygen of antipyrine and forms a stable five- and six-membered chelating ring. From the X-ray crystallographic analysis (XRD) patterns of the ligand and complexes showed the polycrystalline phases are indicated by the multiple diffraction peaks in the 1igand and its complex (5). The HOMO‒LUMO energy gaps (∆E) were used to create theoretical models for the structure and confirmation barriers in molecular systems for the ligand (H2L) and metal complexes. It was found that the Cu(II), Co(II), Ni(II), and Mn(II) complexes have lower values for HOMO‒LUMO energy gaps (∆E), indicating that they are more stable than the 1igand. The biological activities of ligand (H2L) and its metal complexes showed that ligand was stronger antimicrobial and antioxidant agent than its metal complexes. 50 µg/ml H2L caused inhibition zones ranged from 13 to 20 mm against the tested bacteria and 13 to 16 against fungi. In addition, the present study tested metal (II) acetate complexes with a heterocyclic azodye ligand for their application in the textile industry as antimicrobial dyed fabrics. All obtained results confirmed the possibility of using the prepared compounds in different industrial applications. The 1igand (H2L) and its metal complexes showed moderate to strong antimicrobial activities in agar well diffusion, MIC, and antioxidant tests. Ligand and its metal complexes revealed inhibition zones against all tested microbes ranged between 6 to 24 mm. The MIC values of ligand and its metal complexes were recorded at 20 to 30 μg/ml and 30 to 145 μg/ml, respectively. 50 µg/ml of 1igand and its metal complexes was enough to complete inhibit Gram negative E. coli moreover they could inhibit the multidrug resistant bacteria K. pneumoniae and Pseudomonas sp. By molecular docking study, it was found that the complex (1) showed the highest and better binding affinity (-8.38874 and -7.74442 kcal/mol) than other 1igand (H2L) and complexes (2–5) for the breast cancer (3HB5) protein central activity and the colon cancer (2HQ6) protein central activity.

The role of physicochemical and topological parameters in drug design

Quantitative structure activity relationship (QSAR) is a widely used tool in rational drug design that establishes relationships between the physicochemical and topological descriptors of ligands and their biological activities. Obtained QSAR models help identify descriptors that play pivotal roles in the biological activity of ligands. This not only helps the prediction of new compounds with desirable biological activities but also helps with the design of new compounds with better activities and low toxicities. QSAR commonly uses lipophilicity (logP), hydrophobicity (logD), water solubility (logS), the acid–base dissociation constant (pKa), the dipole moment, the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), molecular weight (MW), molar volume (MV), molar refractivity (MR), and the kappa index as physicochemical parameters. Some commonly used topological indices in QSAR are the Wiener index, Platt index, Hosoya index, Zagreb indices, Balaban index, and E-state index. This review presents a brief description of the significance of the most extensively used physicochemical and topological parameters in drug design.

Synthesis, characterization and biological activity of a novel N1, N5-bis[2-hydroxyphenyl]-2-methyl-1,5-diaminopentane Schiff base: Effect of methylene spacers on biological activities

A novel ONNO donor tetradentate Schiff base ligand N,N'-bis[2- hydroxyphenyl]-2-methyl-1,5-diaminopentane (1) is synthesized and characterized by using 1H, 13C NMR spectroscopy and mass spectrometry. Biological studies on newly synthesized ligand are carried out and results are compared with the biological activities of known Schiff base ligands: N,N'-bis[{2- hydroxyphenyl }]-1,4-diaminobutane (2) and N,N'-bis[{2- hydroxyphenyl }]-1,3-diaminopropane (3). This comparative study highlights the effect of increasing methylene linkage on the biological activity of these ligands. The anti-microbial activities of all three ligands have been screened against two distinct gram-positive and gram-negative bacteria. In-vitro results of this comparative analysis are also supported by comprehensive molecular docking studies with DNA gyrase subunit B protein of gram-positive bacterium S. aureus and FabH–CoA complex of gram-negative bacterium E. coli. Experimental studies reveal that the spacer group plays a vital role in controlling the biological activities of the ligand. These findings are in good agreement with the theoretical findings. The study demonstrates that the biological activity of ligands is enhanced with increments in the number of spacers. Thus, the newly synthesized ligand (1) with the most extended spacer among the three showed the highest biological activity compared to other two ligands, similar to the popular drug Ciprofloxacin.

Structural and Spectral studies of new mixed Ligand complexes for 2-Amino-4-nitrophenol with some Metallic ions and Evaluation their Biological Activities

New mixed ligand complexes were prepared from 2-Amino-4-nitrophenol (HL1) with curcumin (HL2) and some metal ions M = [ Mn (II), Co (II), Ni (II), Zn (II), Cd (II), Hg(II)], 1:1:1 Molar ratio by using ethanol as a solvent. The complexes were characterized by spectroscopic measurements (UV spectrum, IR spectrum, mass spectrometry, atomic absorption) along with chlorine content, magnetic sensitivity, melting point, elements analysis (C.H.N), molar conductivity. The octahedral geometry was proposed for all complexes prepared according to the results obtained. The biological activity of ligands and all prepared complexes were estimated for three types of bacterial, are [Bacillus subtilis, Eterobactern and Escherichia Coli). The results shown biological activity against the types of bacteria for most of the synthesized complexes compared with ligands.

Metal contained Phthalocyanines with 3,4-Dimethoxyphenethoxy substituents: their anticancer, antibacterial activities and their inhibitory effects on some metabolic enzymes with molecular docking studies

The compounds (3-6) used in this study were re-synthesized in accordance with our previous study. The inhibitory effect of the complexes on some metabolic enzymes was examined and it was demonstrated that the enzymes inhibited by ligands and their complex molecules at micromolar level. The best Ki value for α-glycosidase enzyme was absorved 1.01±0.08 µM for compound 6. The biological activity of ligand and metal complexes against enzymes was compared with molecular docking method. The enzymes used against ligand and metal complexes respectively: Achethylcholinesterase for ID 4M0E (AChE), butyrylcholinesterase for ID 5NN0 (BChE), α-glycosidase for ID 1XSI (α-Gly). ADME analysis was performed to examine the drug properties of the compounds (3-6). Besides, the anticancer properties of the complexes were studied. The doses of all compounds caused significant reductions in MCF-7 cell viability. The 3 and 5 compounds administered to PC-3 cells exhibited a more pronounced cytotoxic effect than the other two compounds (4 and 6). Furthermore, antibacterial activities of these compounds against Escherichia coli and Staphylococcus aureus were examined. Communicated by Ramaswamy H. Sarma

Synthesis, characterisation, thermal properties and biological activity of coordination compounds of novel selenosemicarbazone ligands

A series of novel metal complexes with bidentate selenosemicarbazone Schiff-base ligands HL1 and HL2 are reported. The reaction of 2-(((3-nitrophenyl)amino)(phenyl) methyl)cyclohexan-1-one and 2-((4-methoxyphenyl)(phenylamino)methyl)cyclohexan-1-one with an ethanolic mixture of KSeCN and NH2NH2 afforded the preparation of the novel selenosemicarbazone ligands (E)-2-(2-(((3-nitrophenyl) amino)(phenyl)methyl)cyclohexylidene)hydrazine-1-carboselenoamide (HL1) and (E)-2-(2-((4-methoxyphenyl)(phenylamino)methyl)cyclohexylidene)hydrazine-1-carboselenoamide (HL2), respectively. The reaction of ligands with Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) metal ions resulted in the formation of mononucleating complexes of general formula K2[ML2Cl2] and [M’L2], (M = Mn(II), Co(II) and Ni(II); M’ = Cu(II), Zn(II) and Cd(II)). The mode of bonding and predicted geometry of complexes were determined through their physico-chemical and spectroscopic measurements. These data indicated the formation of the following; (i) a distorted octahedral geometry about Mn(II), Co(II) and Ni(II), (ii) a distorted square planar around Cu(II), and (iii) a tetrahedral arrangement about Zn(II) and Cd(II) ions. The thermal properties and biological activity of ligands and their metal complexes were studied. The title ligands and their metal complexes were screened against Gram negative bacterial strains; Escherichia coli (E. coli), Bacillus sabtuius and Klebsiella pneumoniae and Gram positive bacterial strain Staphylococcus aureus that revealed the metal complexes become more potentially resistive to the microbial activities, compared to the free ligands. Further, selenosemicarbazone ligands and their complexes were examined for their antifungul activity towards Candida albicans, Candida glabrata, Candida tropicalis and Candida parapsilsis, which generally showed complexes are more active compared to the free ligands.

Indole-derived water-soluble N, O bi-dentate ligand-based mononuclear transition metal complexes: in silico and in vitro biological screening, molecular docking and macromolecule interaction studies

A novel tryptophan-derived Schiff base ligand (potassium (E)-2-((4-chloro-3-nitrobenzylidene)amino)-3-(1H-indol-3-yl)propanoate) and a series of its transition metal complexes of the types [ML2] and [ML(1,10-phen)2]Cl where M = Cu(II), Co(II), Ni(II) and Zn(II) were prepared. They were analyzed by various spectral and physicochemical studies. The XRD data were also used to determine the average lattice parameters and crystalline size of the compounds. All the synthesized compounds were tested against a series of five bacterial and fungal strains. The obtained results showed that the biological activity of free ligand was increased on complexation. PASS online software predicts the various biological activities of ligand such as enzyme inhibitor, antiviral, analgesic and antituberculosis. The in silico theoretical prediction of synthesized compounds is also deliberated by Swiss ADME predictor which gives the properties of molecular hydrophobicity (log P), topological polar surface area (TPSA) and oral bioavailability score. The binding energy of the docked molecule with macromolecules 1BNA and 3EQM is also determined by using Hex 8.0 software. The ligand has the least binding energy score which signifies that the potential of binding is greater in the receptor. Moreover, the interactions of complexes with DNA have been explored by electronic absorption titration, fluorescence emission titration, viscosity measurements and gel electrophoresis.HighlightsSynthesis and characterization of novel indole-derived compounds.X-ray diffraction studies demonstrate average crystalline size of the compounds.Metal complexes act as good metallointercalators.Metal complexes show higher antimicrobial activity compared to ligand.Prediction of biological activities of the ligand by PASS online software.Drug-like nature and bioavailability of synthesized compounds predicted by Swiss ADME predictorDocking of the synthesized compounds with 1BNA and 3EQM using HEX 8.0 software.Communicated by Ramaswamy H. Sarma

Synthesis, spectral, and in vitro antimicrobial studies of organosilicon(IV) complexes with Schiff bases derived from dehydroacetic acid

Some new di and tri-organosilicon complexes of type R2Si(L1)Cl, R3Si(L1), and R2Si(L2)/R2Si(L3) (R = Me, Et, Bu, and Ph; L1 = 4-hydroxy-6-methyl-3-[1-(quinolin-8-ylimino)ethyl]pyran-2-one, L2 = 3-[1-(2-aminophenylimino)ethyl]-4-hydroxy-6-methylpyran-2-one, and L3 = 3-[1-(2-amino-4-chlorophenylimino)ethyl]-4-hydroxy-6-methylpyran-2-one) were synthesized from Schiff base ligands derived from 8-aminoquinoline/o-phenylenediamine/4-chloro-o-phenylenediamine with dehydroacetic acid. All the compounds were characterized with the help of molar conductance measurements, elemental analyses, UV–Vis, IR, 1H, 13C, 29Si NMR, and mass spectroscopy. On the basis of all these studies, penta-coordinated environment around central silicon atom in 1:1 molar ratio was proposed. The ligands and their organosilicon complexes were tested in vitro for antibacterial activity against Gram-positive bacteria viz. Staphylococcus aureus, Bacillus subtilis as well as Gram-negative bacteria viz. Escherichia coli and antifungal activity against Aspergillus niger. Antimicrobial activity results indicated that biological activity of ligands was enhanced on complexation with organosilicon group and phenyl derivatives were found to be more effective antimicrobial agents as compared to other complexes. Further, docking simulation of four compounds against E. coli topoisomerase II DNA gyrase B were carried out.

Synthesis, Characterization and Antibacterial of 2,3-Dihydrobenzo Thiazole-2-Carboxylic Acid Complexes with Some Selected Metal Ions

A new ligand 2,3-dihydrobenzo [d] thiazole-2-carboxylic acid (L) has been prepared from the reaction of ortho amino phenyl thiol with dichloroacetic acid in mole ratio (1:1). It has been characterized by elemental analysis (C.H.N.), IR, UV- Vis.spectraand 1H, 13C-NMR. A new series complexes of the bivalent ions (Co, Ni, Cu, Pd, Cd, Hg and Pb) and the trivalent (Cr) have been prepared and characterized too. The structural has been established by elemental analysis (C.H.N.), IR, UV-Vis. spectra, molar conductivity, atomic absorption and magnetic susceptibility measurements. The synthesized complexes were prepared in (1:2) ratio correspond to (Co(II), Ni(II), Cu(II), Pd(II), Cd(II), Hg(II) and Pb(II) complexes while in case Cr(III) complex is (1:1) ratio (M:L). ?, Kf for (Cr(III), Co(II), Ni(II) and Cu(II)) were estimated too. The complexes showed characteristics octahedral geometry with the (O,N) ligand coordinated in bidentate mode except with Pd showed square planer. The study of biological activity of ligand (L) and its complexes showed various activities toward Staphylococcus aureusand E. coli.

Spectroscopic Studies, Biological Activity, and Cytotoxicity of Some Binary and Ternary Palladium and Platinum Complexes of Certain Heterocyclic Ligands

Binary and ternary palladium and platinum complexes were synthesized from [MCl4]2− with certain heterocyclic ligands containing nitrogen and oxygen donors and a secondary ligand (pyridine or bipyridine). Complexes were characterized by elemental analysis, mass, IR, and 1H NMR spectroscopy. Biological activities of ligands and complexes against the Escherchia coli and Staphylococcus aureus bacteria, and the two fungi Aspergillus flavus and Candida albicans were screened. The cytotoxicity of the two complexes [Pt(PCA)(Py)(Cl)]Cl and [Pt(PCA)(μ-Cl)2(Bpy)]Cl2 were checked as antitumor agents on two breast cancer and liver carcinoma cell lines. They exhibited higher in vitro activities toward the tumors relative to cisplatin.

Synthesis of Sulfonamides, Metal Complexes and the Study of In vitro Biological Activities

A modified method for the synthesis of a series of substituted benzenesulfonamides from benzenesulfonylchloride and substituted amines (1:1) in aqueous media have been adopted at controlled pH (8-10). Transition metal complexes of synthesized ligands were also prepared by refluxing ligands and metal salts (2:1) for one hour. The synthesized compounds have been characterized by spectroscopic techniques (FTIR, 1HNMR and mass spectrometry). Synthesized compounds were analyzed for their activity toward acetyl cholinesterase (AChE) inhibition, butyrylcholinesterase (BChE) inhibition, lipoxygenase (LOX) inhibition, antioxidant (DPPH) and antiurease. As regards biological activities of ligands, only N-(2-nitrophenyl) benzenesulfonamide (3) showed appreciated value of IC50= 77.13± 00 mole against LOX while all metal complexes showed low activities. Cu complex (C-4) showed moderate activity against LOX while all the other metal complexes had no activity against any enzyme at all. Similarly Zn complexes (Z-2 to Z-6) showed little activity against AChE but the ligands showed no significant activity against any other. Metal complexes showed high capacity toward antiurease activity. Keywords: Sulfonamides, metal complexes, biological activity, anti-enzyme activity.

Synthetic, Spectroscopic, and Biological Aspects of Triorganosilicon(IV) Complexes of Tridentate Schiff Bases

Hexacoordinated organosilicon complexes of type R3Si(L) (R = ethyl, butyl, phenyl; HL = ligand, obtained by the condensation of 4-aminoantipyrine with 2-hydroxyacetophenone, 2-hydroxybenzophenone, 2-hydroxybenzaldehyde, and 2-hydroxynapthaldehyde) have been synthesized and characterized by elemental analysis, molar conductance, and spectroscopic studies (IR, 1H, 13C, and 29Si NMR). The spectroscopic studies indicated that the ligands acted as tridentate coordinating through azomethine nitrogen, carbonyl oxygen, and oxygen of hydroxyl after deprotonation to the central silicon atom. The ligands and their organosilicon complexes have been evaluated for antimicrobial activities against fungi (Aspergillus niger and Candida albicans), and against Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis), and Gram-negative bacteria (Escherichia coli). The aim of the present work is to synthesize novel eco-friendly fungicides and bactericides and to study the effect of the biological activity of ligands on the complexation with organosilicon moiety. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Synthesis and biological activity of a ferrocenyl ligand derived from thiophenol and its coordination with some transition metals

The new ferrocenyl ligand 1,1′-bis(2,3-dihydro-2-methylbenzo[d]thiazol-2-yl)ferrocene was prepared at room temperature from the condensation reaction of 2-aminothiophenol with 1,1′-diacetylferrocene followed by intramolecular Michael-type addition. The prepared ligand forms 1:1 complexes with manganese(II), cobalt(II), nickel(II), copper(II), and zinc(II) in good yield. Characterization of the ligand and its complexes was carried out using IR, 1H and 13C NMR, electronic absorption, mass spectra, magnetic susceptibility, molar conductance, and elemental analysis. Biological activity of the ligand and its complexes was assessed against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Alcaligenes faecalis, Aspergillus niger, and Candida albicans. The results indicated that the ligand is biologically active but the complexes are more active. The Zn and Cu complexes exhibited biological activity comparable to that of chloramphenicol (commercial broad-spectrum antibiotic).

Synthesis, structural studies and biological activity of dioxomolybdenum(VI), dioxotungsten(VI), thorium(IV) and dioxouranium(VI) complexes with 2-hydroxy-5-methyl and 2-hydroxy-5-chloroacetophenone benzoylhydrazone

New complexes of MoO2(VI), WO2(VI), Th(IV) and UO2(VI) with aroyl hydrazones have been prepared and characterized by various physicochemical methods. Elemental analysis suggested 1 : 1 metal : ligand stoichiometry for MoO2(VI), WO2(VI), and UO2(VI) complexes whereas 1 : 2 for Th(VI) complexes. The physicochemical studies showed that MoO2(VI), Th(IV) and UO2(VI) complexes are octahedral. The electrical conductivity of these complexes lies in the range 1.00 × 10−7−3.37 × 10−11Ω−1 cm−1 at 373 K. The complexes were found to be quite stable and decomposition of the complexes ended with respective metal oxide as a final product. The thermal dehydration and decomposition of these complexes were studied kinetically using both Coats-Redfern and Horowitz-Metzger methods. It was found that the thermal decomposition of the complexes follow first order kinetics. The thermodynamic parameters of the decomposition are also reported. The biological activities of ligands and their metal complexes were tested against various microorganisms.

Pair wise binding affinity: 3D QSAR studies on a set of triazolo [1, 5-a] quinoxalines as antagonists of AMPA and KA receptors

The glutamate receptor system is implicated in the development and maintenance of epileptic seizures and it has been reported that compounds showing high affinity for both AMPA and KA binding sites are more potent anticonvulsants than compounds having selective affinity toward AMPA or KA receptor. These outcomes make such inhibitors future potential antiepileptic drugs. So, the pair wise binding affinity for AMPA and KA receptors inhibition was proposed by using the addition between biological activities of ligands. This approach for evaluation of pair wise binding affinity was exemplified using set of triazolo [1,5-a] quinoxaline for AMPA and KA receptors. The biological activity towards AMPA and KA receptors (expressed as -log IC5O) was taken as a dependent variable for building CoMFA and CoMSIA models. The resulting models show the ways of increasing binding affinity to both AMPA and KA receptors as potential target for epilepsy. The statistically significant results show that pair wise CoMFA and CoMSIA models are better then individual models. The resulting cross-validated r2CV value 0.806 for CoMFA is greater then 0.780 for CoMSIA pair wise model. The non-cross validated run giving a coefficient of determination r2 value of 0.946 and 0.908 for CoMFA and CoMSIA respectively, provided a good correlation between the observed and computed affinities of the compounds.

Structural Response of the Estrogen Receptor Ligand Binding Domain to Selective Ligand Binding by Spin Label Distance Measurements

Estrogen Receptor‐α (ER‐α) is a nuclear hormone receptor that has become an important therapeutic target for tissue‐specific inhibitors. It has been suggested that the dynamics and conformations of the helix 12 (H12) region of the ERα ligand binding domain (LBD) are affected by ligand and coregulator binding. In agonist form, H12 is stabilized by folding over the binding pocket, forming a surface where coregulators bind. Antagonists disrupt this folding, inhibiting the coregulator binding that is necessary for ER‐α to carry out its downstream effects. Selective estrogen receptor modulators (SERMs) show tissue‐selective anti‐estrogenic activity. It has been suggested that SERMs partially disrupt coactivator binding by displacing H12. To investigate this possibility, H12 was spin‐labeled at residue 543 and at residue 530 in the H12 hinge. Changes in structure induced by binding a series of agonist to antagonist ligands and coregulator peptide SRC1 were observed by measuring interspin distances using double electron‐electron resonance (DEER). DEER showed that ligand binding induces dynamic changes that directly correlate with the ligand's biological activity. These results demonstrate the importance of characterizing receptor‐ligand dynamics that are unavailable from standard structural methods.

Constitutive deletion of the serotonin-7 (5-HT 7) receptor decreases electrical and chemical seizure thresholds

The localization of serotonin-7 (5-HT(7)) receptors and the biological activity of ligands have suggested that 5-HT(7) receptors might be involved in pain, migraine, epilepsy, anxiety, depression, memory, and sleep. In the present study, the potential involvement of 5-HT(7) receptors in epilepsy and other seizure disorders was assessed by comparing the seizures produced by three types of electrical stimulation and three chemical convulsants in 5-HT(7) receptor-deficient (knockout, KO) mice to those seizures observed in wild-type (WT) mice. Thresholds for producing electroshock-induced clonic seizures did not differ between KO versus WT mice. However, thresholds for producing electroshock-induced tonic seizures were significantly lower in KO than in WT mice. Seizures produced by pentylenetetrazole (PTZ, a GABA(A) receptor antagonist), N-methyl-d-aspartate (NMDA, an agonist at NMDA-type glutamate receptors), and cocaine (an inhibitor of monoamine uptake) were also studied. PTZ was more potent in inducing seizures in 5-HT(7) KO mice than in wild-type mice. Likewise, cocaine was more potent in inducing seizures in 5-HT(7) KO than in WT mice; moreover, death resulted from cocaine administration in 5-HT(7) KO mice but not in WT mice. There was a similar trend for NMDA that did not reach statistical significance. The present findings point to the potential for a generalized reduction in seizure threshold with constitutive deletion of the 5-HT(7) receptor gene. Since seizures have not been reported with pharmacological blockade of the receptor, the findings suggest that adaptive changes may play a role in the low seizure thresholds in these mice. In addition, the data suggest that the lower thresholds for seizures produced by diverse mechanisms should be taken into account when interpreting other aspects of the phenotype and behavioral pharmacology of this mouse.

A Kinetic Analysis of the Conformational Flexibility of Steroid Hormones

For a set of 10 androgen steroids and estradiol (E2), the kinetic feasibility of conformation flexibility of the cyclic moieties was studied under the constraint of maintaining the ByC trans and CyD trans ring fusion of the natural and biologically active enantiomer. To this end, the conformational energy surface was quantified using the semiempirical quantum chemical AM1 model. The computational analysis included the location of Conformational transition states with associated barriers, and intrinsic reaction coordinate (IRC) calculations to characterize the trajectories of the rotations and the relationships of the transition states to neighbouring chair and twist conformations. Conformational transformations were observed only for the A and B rings except for E2, which yielded corresponding transformations for the B and C ring, respectively. Interestingly, the rotation barriers starting from the lowest-energy conformations differed substantially, ranging from below 10 kJymol for four compounds to 18 ‐ 20 kJymol for another five compounds. Moreover, chair and twist conformations were found only for steroids with higher saturated rings, while semichairs and semitwists occurred for steroids with aromatic or partly unsaturated rings, and B-ring transformations lead to kinetically unstable conformations with very flat energy minima. Although the rotation barriers for most of the transitions are clearly above the thermal energy (kT) at room temperature when evaluated relative to the lowestenergy conformations, the associated energy demands are well below the gain in energy from ligand-receptor binding. The results suggest that conformer interconversion are feasible from both a thermodynamic and kinetic perspective, and support previous investigations in which conformer distributions rather than lowest energy conformations were considered when assessing hormone receptor topography and the biological activity of ligands.