Macrocyclic Ring Structure Research Articles

Fragment-based structural exploration and chemico-biological interaction study of HDAC3 inhibitors through non-linear pattern recognition, chemical space, and binding mode of interaction analysis

HDAC3 is an emerging target for the identification and discovery of novel drug candidates against several disease conditions including cancer. Here, a fragment-based non-linear machine learning (ML) method along with chemical space exploration followed by a structure-based binding mode of interaction analysis study was carried out on some HDAC3 inhibitors to obtain the key structural features modulating HDAC3 inhibition. Both the ML and chemical space analysis identified several physicochemical and structural properties namely lipophilicity, polar and relative polar surface area, arylcarboxamide moiety, bulky fused aromatic group, n-alkyl, and cinnamoyl moieties, the higher number of oxygen atoms, π-electrons for the substituted tetrahydrofuronaphthodioxolone moiety favorable for higher HDAC3 inhibition. Moreover, hydrogen bond forming capabilities, the length and substitution position of the linker moiety, the importance of phenyl ring in the linker motif, the contribution of heterocyclic cap moieties for effective inhibitor binding at the HDAC3 catalytic site that correspondingly affects the HDAC3 inhibitory potency. Again, macrocyclic ring structure and cyclohexyl cap moiety are responsible for lower HDAC3 inhibition. The MD simulation study of selected compounds explained strong binding patterns at the HDAC3 active site as evidenced by the lower RMSD and RMSF values. Nevertheless, it also explained the importance of the crucial structural fragments derived from the fragment-based analysis during ligand-enzyme interactions. Therefore, the outcomes of this current structural analysis will be a useful tool for fragment-based drug discovery of effective HDAC3 inhibitors for clinical therapeutics in the future. Communicated by Ramaswamy H. Sarma

Synthesis, crystal structure, molecular dynamics, docking and in-vitro studies of cyclododecanonethiosemicarbazone, a promising anti tuberculosis agent

Cyclododecanonethiosemicarbazone (CDT), crystallises in triclinic crystal system in spacegroup P-1 having unit cell parameters as a = 5.6152(2)Å, b = 8.3747(4) Å, c = 16.1901(7) Å, α = 91.186(2)°, β = 90.880(2)° and γ = 108.014(2)°, V = 723.68(5) Å3 and Z = 2.The macrocyclic ring structure shows close resemblance to the most stable conformation for a 12 membered aliphatic cyclic ketone, where three C-C bonds are present on each side of the heavy atom framework's square structure. Existence as thione form of the compound is confirmed by IR, NMR and Crystallographic data. There is extensive electron delocalisation along its thiosemicarbazone moiety. A number of short term interactions, including three intermolecular H-bonding interactions involving each S, forms infinite interlinked chains of molecules along a axis. Results of anti tuberculosis activity studies reveal that minimum inhibitory concentration (MIC) of CDT is 800 µg/mL for the test organism Mycobacterium smegmatis. Hirshfeld surface analysis, docking and molecular dynamics studies suggest stable protein –ligand binding with the related 1TEX protein.

Triorganotin(IV) derivatives with semirigid heteroditopic hydroxo‐carboxylato ligands: Synthesis, characterization, and cytotoxic properties

Three organic hydroxy‐carboxylic acids separated by a semirigid aromatic diaza scaffold and carrying alkyl groups of different steric hindrance (H′HL1, cyclopropyl; H′HL2, cyclohexyl; H′HL3, adamantyl) were employed as pro‐ligands. Their reaction with suitable triorganotin precursors leads to 10 complexes of compositions: [Me3Sn(HL1)]n·0.5nC6H5CH3 1, [Et3Sn(HL1)]n 2, [nBu3Sn(HL1)]n 3, [Ph3Sn(HL1)]n 4, [Me3Sn(HL2)]2·2CH2Cl2 5, [Et3Sn(HL2)]2 6, {[nBu3Sn(HL2)][nBu3Sn(HL2)(H2O)]} 7, [Ph3Sn(HL2)]n·nC2H5OH 8, [nBu3Sn(HL3)]n 9, and [Ph3Sn(HL3)]n 10. The solid‐state structures of 1–10 were deduced from single‐crystal X‐ray diffraction studies along with two of the pro‐ligands: H′HL1 and H′HL2. In the solid state, four different extended structure types were observed. In compounds 1–3 with aliphatic substituents at the tin atoms and a small substituent at the ligand backbone (cyclopropyl), 1D coordination polymers based on carboxylate bridging were observed, whereas compounds 4 and 8–10 with large substituents attached to the metal and the ligand (cyclohexyl and adamantyl) were 1D coordination polymers based on heteroditopic binding of the ligands. Albeit having essentially the same ligand conformation, the compounds having smaller substituents at the tin atoms (5, R = Me; 6, R = Et) comprise 24‐membered macrocyclic ring structures. In 7, water molecules are coordinated to half the tin atoms, giving dinuclear fragments {[HL2][nBu3Sn][HL2][nBu3Sn(H2O)]}, which are linked through OwH···Osal hydrogen bonds into 1D hydrogen‐bonded tapes. In solution, the tin atoms in 1–10 are coordinated to a single monoanionic [HL1–3]− ligand molecule utilizing anisobidentate coordination with the carboxylate group, as revealed from 119Sn nuclear magnetic resonance spectral results. The antiproliferative activity of the tri‐n‐butyl and triphenyltin compounds 3, 4, and 7–10 was evaluated against the cervical cancer cells (HeLa) and normal kidney cells (HEK) using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Of these, the adamantyl‐substituted tin complexes 9 and 10 present increased activity with IC50 values of 0.51 ± 0.01 and 0.41 ± 0.03 (μM) and good selectivity. The cell death mechanism was identified as apoptosis based on dual staining with fluorescent dyes (Hoechst 33342/propidium iodide and acridine orange/ethidium bromide) and might be related to reactive oxygen species.

Macrocyclic effect on inhibitory activity: a modeling study on MerTK inhibitors

Macrocyclic ring structures could have drug-like properties such as membrane permeability, metabolic stability, binding affinity, selectivity, and high-biological activities. Synthesized macrocyclic inhibitors have been studied and the effect of ring size has gained attention from drug design community. Marsault et al. showed a positive correlation between ring size and inhibitory activity against rennin. On the other hand, De Clercq et al. suggested that there would be some optimum ring size for histone deacetylase inhibitory activity. Therefore, macrocyclic effects appear elusive while intriguing. In this study, we have selected a large set of macrocyclic inhibitors (14–20-membered rings) to study macrocyclic effect on MerTK using molecular modeling techniques. We carefully positioned all the cyclic inhibitors into the binding pocket utilizing available information obtained from both experimental and theoretical means. Then, from the resultant binding poses, the ligand–receptor interactions were analyzed. Unlike previous reports, we could not observe any relevance between ring size and inhibitory activity. However, there is a correlation between the number of hydrogen bonds and inhibitory activity. Among these hydrogen-bonding interactions, active site residues Arg727, and Asn728 as well as two signature interactions at the hinge region were found to be crucial for MerTK inhibition. Furthermore, the importance of number of hydrogen bonding was further validated statistically by means of 3D-QSAR techniques such as CoMFA and CoMSIA. The involvement of Arg727 and Asn728 was checked graphically by CoMSIA hydrogen-bonding donor map. This outcome could be helpful for more potent MerTK inhibitor design. In addition, more detailed studies on ring size effect would be desirable to understand macrocyclic effects.

Beryllium Complexes with Bio‐Relevant Functional Groups: Coordination Geometries and Binding Affinities

The coordination mode around beryllium in proteins and the binding affinity towards the peptide are unknown because there have been no coordination compounds of beryllium with ligands bearing bio-relevant functional groups. We report the first comprehensive study on Be complexes with monodentate carboxylic acids, esters, aldehydes, and alcohols. Through solution and solid-state techniques we determined that the binding affinities of Be2+ ions towards the functional groups are: carboxylate > alcohol > aldehyde > ester. Crystal structures of all the compounds have been determined including the unprecedented dodeca-nuclear macrocyclic ring structure of non-basic beryllium benzoate, which is the first example of those beryllium carboxylates. These findings enable the evaluation of potential beryllium binding sites inside proteins and is required to understand the mechanism of metal-triggered immune responses.

Synthesis of Molecular Nanohoops Bearing a Tetrahydro[6]cycloparaphenylene Fused to a Hydrogenated or a Bithiophene-Inserted Cycloparaphenylene.

A synthetic pathway to a molecule bearing two molecular nanohoops, including a tetrahydro[6]cycloparaphenylene (4H[6]CPP) fused through two 1,4-dimethoxybenzene units to a 4H[10]CPP, was developed. Similarly, a molecule containing a 4H[6]CPP fused through two 1,4-dimethoxybenzene units to a molecular nanohoop bearing a [6]CPP inserted with two 2,2'-bithiophene-5,5'-diyl groups was synthesized. The Diels-Alder reactions of two (E,E)-1,4-diaryl-1,3-butadienes with 1,4-benzoquinone and the Ni-mediated homocoupling reactions are the key steps for the construction of macrocyclic ring structures. Oxidative aromatization with DDQ converted a hydrogenated system to a fully aromatized nanohoop with 10 aromatic units, including a [6]CPP inserted with two 2,2'-bithiophene-5,5'-diyl groups. The UV-vis and fluorescence spectra of the fused two-hoop systems were investigated.

Synthesis, structure and property of diorganotin complexes with chiral N-(5-chlorosalicylidene)valinate ligand

Six new diorganotin N-[(5-chloro-2-oxyphenyl)methylene]valinates, R2SnL (R = Me, 1; Et, 2; L = 5-Cl-2-OC6H3CH = NCH(i-Pr)COO: (S)-, a; (R)-, b; (RS)-, c), have been synthesized from the reaction of R2SnCl2 with the chiral ligand KHL (potassium salt of HL) in different solvents and characterized by elemental analysis, IR, NMR (1H, 13C and 119Sn) spectra. In benzene, the configuration of the chiral ligand was retained. (S)-Enantiomers (1a and 2a) and (R)-enantiomers (1b and 2b) display discrete molecular structures with distorted trigonal bipyramidal geometries in which two C atoms of organic groups (R) and the imino N atom occupy the equatorial positions and a phenoxide O and an unidentate carboxylate group O atom are in the axial orientation. In the methanol, the chiral ligand was racemized. 1c⋅MeOH is a centrosymmetric dimers formed by (R)- and (S)- enantiomers through two SnO⋅⋅⋅Sn bridges. The coordination geometry of the Sn atom can be described as a distorted pentagonal bipyramid with two methyl groups in axial positions. The crystal of 2c is composed of two threefold symmetric trimers, a [Et2SnL-(R)]3 and a [Et2SnL-(S)]3, with a macrocyclic 12-membered ring structure formed by the bidenate bridging coordination of carboxylate group to tin atoms. Each tin atom is six-coordinated in distorted [SnC2NO3] octahedron geometry. The fluorescence properties of ligand KHL and complexes 1 (1a-1c) and 2 (2a-2c) have been measured. The results show the complexes may be explored for potential luminescent materials.

Synthesis and Structure of a Functionalized [9]Cycloparaphenylene Bearing Three Indeno[2,1-a]fluorene-11,12-dione-2,9-diyl Units.

A synthetic pathway to a functionalized [9]cycloparaphenylene bearing three indeno[2,1-a]fluorene-11,12-dione-2,9-diyl units in the macrocyclic ring structure ([3]CIFO) has been developed. The 1H and 13C NMR spectra show that only the anti rotamer (anti-[3]CIFO) is produced. DFT calculations indicate that the anti rotamer is thermodynamically more stable than the syn rotamer by 4.3 kcal/mol, and the rotational barrier from the anti to syn rotamer is estimated to be 23.3 kcal/mol. The UV-vis and fluorescence spectra and cyclic voltammogram of anti-[3]CIFO were investigated.

Dinuclear organotin(IV) coordination polymers derived from Schiff bases with l-aspartic acid

Reaction of sodium 2-((E)-((Z)-4-hydroxypent-3-en-2-ylidene)amino)succinate and sodium (E)-2-((1-(2-hydroxyphenyl)ethylidene)amino)succinate (L1HNa2 and L2HNa2) in a 1:2 M ratio with Bz2SnCl2 in methanol gave dinuclear diorganotin(IV) complexes of composition [Bz2Sn(Lx)SnBz2Cl] (Lx = L1 (1) and L2 (2)). Reaction of L2HNa2 and Bz3SnCl (1:2) in anhydrous toluene under reflux conditions yielded the analogous chlorine-free product of composition [Bz2Sn(L2)SnBz3] (3) via cleavage of a Sn-C bond for one of the triorganotin precursor equivalents with elimination of toluene. In addition, the tributyltin(IV) compounds of composition [Bu3Sn(LxH)SnBu3] (Lx = L2 (4) and L3 (5)) were prepared in a single-step transformation by combining equimolar proportions of (Bu3Sn)2O, (S)-2-aminosuccinic acid and 2'-hydroxyacetophenone/2-hydroxybenzaldehyde in anhydrous methanol. The structures of the organotin(IV) compounds in solution were assessed using 1H, 13C and 119Sn NMR spectroscopic techniques, while the molecular structures of 1–5 were analyzed by single-crystal X-ray diffraction. In the solid state, complexes 1-3 exhibit one-dimensional coordination polymers with alternate six- and seven-coordinate tin atoms embedded in distorted monocapped trigonal-bipyramidal (1-2)/octahedral (3) and pentagonal-bipyramidal (1-2)/bicapped trigonal-bipyramidal (3) coordination environments. On the contrary, compounds 4–5 are two-dimensional coordination polymers based on 30-membered tetranuclear macrocyclic ring structures, in which the tin atoms comprise distorted trigonal-bipyramidal coordination polyhedra. However, in solution the polymeric structures of 1–5 dissociate to give dinuclear complexes, even in non-coordinating solvents such as chloroform.

Improving the Binding Affinity of in-Vitro-Evolved Cyclic Peptides by Inserting Atoms into the Macrocycle Backbone.

Cyclic peptides binding to targets of interest can be generated efficiently with powerful in vitro display techniques, such as phage display or mRNA display. The cyclic peptide libraries screened with these methods are generated by altering in a combinatorial fashion the amino acid sequence of the peptides, the number of amino acids in the macrocycle rings, and the cyclization chemistry. A structural element that cannot easily be varied in the cyclic peptides is the backbone, which is built from amino acids, each of which contributes three atoms to the macrocyclic ring structure. Here, we proposed to improve the affinity of a phage-selected bicyclic peptide inhibitor of coagulation factor XII (FXII) by screening variants with one or two carbon atoms inserted into different positions of the backbone, and thus tapping into a structural space that was not sampled by phage display. Two mutants showed 4.7- and 2.5-fold improved Ki values. The better one blocked FXII with a Ki of 1.5±0.1 nm and inhibited activation of the intrinsic coagulation pathway (EC2x 1.7 μm). The strategy of ring size variation by one or several atoms should be generally applicable for the affinity maturation of in-vitro-evolved cyclic peptides.

Synthesis, Structure, and Molecular Recognition of S6‐ and (SO2)6‐Corona[6](het)arenes: Control of Macrocyclic Conformation and Properties by the Oxidation State of the Bridging Heteroatoms

We report herein the synthesis, structure, and molecular recognition of S6 - and (SO2 )6 -corona[6](het)arenes, and demonstrate a unique and efficient strategy of regulating macrocyclic conformation and properties by adjusting the oxidation state of the heteroatom linkages. The one-pot nucleophilic aromatic substitution reaction of 1,4-benzenedithiol derivatives, biphenyl-4,4'-dithiol and 9,9-dipropyl-9H-fluorene-2,7-dithiol with 3,6-dichlorotetrazine afforded S6 -corona[3]arene[3]tetrazines. These compounds underwent inverse-electron-demand Diels-Alder reaction with enamines and norbornadiene to produce S6 -corona[3]arene[3]pyridazines. Facile oxidation of sulfide linkages yielded (SO2 )6 -corona[3]arene[3]pyridazines. All corona[6](het)arenes adopted generally hexagonal macrocyclic ring structures; however, their electronic properties and conformation could be fine-tuned by altering the oxidation state of the sulfur linkages. Whereas (SO2 )6 -corona[3]arene[3]pyridazines were electron-deficient, S6 -corona[3]arene[3]pyridazines acted as electron-rich macrocyclic hosts that recognized various organic cations in both aqueous and organic solutions.

Syntheses and Structures of Thiophene-Containing Cycloparaphenylenes and Related Carbon Nanohoops

Thiophene-containing cycloparaphenylenes (CPPs) bearing 8, 10, and 16 aromatic and heteroaromatic units in the macrocyclic ring structures were synthesized. Specifically, two and four thiophene-2,5-diyl units were incorporated into functionalized [6]- and [12]CPP macrocyclic carbon frameworks, respectively. In addition, two 2,2'-bithiophene-5,5'-diyl units were inserted into a functionalized [6]CPP carbon framework. The cyclic and differential pulse voltammetry and the UV-vis and fluorescence spectra of the fully aromatized macrocycles and their precursors exhibited interesting electrochemical and optical properties.

Tuning the Supramolecular Structure through Variation of the Ligand Geometry and Metal Substituents–Diorganotin Macrocycles and Coordination Polymers Derived from cis- and trans-1,2-, 1,3-, and 1,4-Cyclohexanedicarboxylic and cis,cis-1,3,5-Cyclohexanetricarboxylic Acid

cis- and trans-1,2-chdcaH2, 1,3-chdcaH2, and 1,4-chdcaH2 (chdcaH2 = cyclohexanedicarboxylic acid) as well as cis,cis-1,3,5-chtcaH3 (chtcaH3 = cyclohexanetricarboxylic acid) have been treated with dimethyl- and di-n-butyltin reagents, and for the case of 1,4-chdcaH2 additionally with di-tert-butyltin dichloride, to determine whether macrocyclic or polymeric diorganotin dicarboxylates are formed dependent of the spatial orientation of the coordinating ligand functions and the organic substituents at the metal atom and to analyze conformational and topological variations in the resulting supramolecular aggregates. The single-crystal X-ray diffraction studies showed that besides the ligand geometry the substituents at the metal center are key elements for the formation of either monomeric, cyclo-oligomeric, or polymeric assemblies. Two of the compounds characterized by X-ray diffraction analysis exhibited macrocyclic ring structures, [{Me2Sn(cis-e,a-1,4-chdca)}2] and [{nBu2Sn(cis-e,a-1,4-chdca)}4]. For most o...

41-Azido-41-deoxyrapamycin

The title compound, C51H78N4O12, is a derivative of rapamycin, a triene macrolide anti­biotic mol­ecule isolated from Streptomyces hygroscopicus. The macrocyclic ring structure has 15 chiral centres, with one of the substituent hy­droxy groups giving an intra­molecular hydrogen bond to a ketone O-atom acceptor. The mol­ecules also form inter­molecular hy­droxy–ketone O—H⋯O hydrogen-bonding associations, giving one-dimensional chains extending along (010). The crystal has 108 Å3 solvent-accessible voids.

Mutual influence of backbone proline substitution and lipophilic tail character on the biological activity of simplified analogues of caspofungin

The echinocandins represent the most recent class of antifungal drugs. Previous structure-activity relationship studies on these lipopeptides have relied mainly upon semisynthetic derivatives due to their complex chemical structures. A successful strategy for the rapid enantioselective synthesis of the branched fatty acid chain of caspofungin and analogues was developed to synthesize several simplified analogues of caspofungin. The specific minimum inhibitory activity of each mimic was determined against a panel of Candida strains. This approach gave access to new fully synthetic derived caspofungin mimics with high and selective antifungal activities against Candida strains. In addition, the data suggested an important role of the hydroxy proline residue in the bioactive conformation of the macrocyclic peptide ring structure.

Anion and Length‐Modulated Bidentate N‐Donor Ligand Controlled Zn(II) Metal‐Organic Frameworks

AbstractTwo metal complexes [Zn2(BTE)2Cl4](1a) and [Zn(BTEE)Cl2](1b) and two coordination polymers [Zn(BTE)2(NO3)2]n (2) and {[Zn(BTE)2(H2O)2](ClO4)2·2H2O}n (3·2H2O, abbreviated in 3) constructed from two structurally related ligands, 2,2′‐bis(1H‐1,2,4‐triazolyl)ether (BTE) and 2,2′‐bis(1H‐1,2,4‐triazolyl)ethoxyethane (BTEE) have been synthesized. Complexes 1a and 1b display zero‐dimension macrocyclic ring structures, while coordination polymers 2 and 3 exhibit one‐dimension chain and two‐dimension corrugated sheet, respectively. Then, intermolecular hydrogen bonding interactions in 1–3 expand those lower dimension structures to extended frameworks.

Metal–organic frameworks with oxazoline-containing tripodal ligand: structure changes via reaction medium and metal-to-ligand ratio

Six new copper(I) complexes [Cu2(L)2(H2O)](ClO4)2 (1), [Cu3(L)2(CH3CN)3(ClO4)3] (2), [Cu2(L)2Cl]ClO4·(9/4)H2O·(3/4)CH3CN (3), [Cu2(L)2(CH3CN)2](ClO4)2·2H2O (4), [Cu2(L)Br2] (5) and [Cu4(L)2Br4]·2CH3CN (6) [L = 1,3,5-tris(2-oxazolinyl)benzene] were prepared by reactions of ligand L with Cu(I) salts. Complexes 1 and 2 obtained by using the same reactants, but different solvents have 1D chain and trinuclear propeller-shaped M3L2 cage-like structures, respectively. While 3 and 4 with 2D (42·62·82)(4·62)(4·62) topological network and M2L2 macrocyclic ring structures were synthesized by addition of CuCl and CuBr, respectively. Complexes 5 and 6 with different structures were isolated by changing the metal-to-ligand ratios. 5 is an infinite 1D chain while 6 is a 3D framework with (4·122)2(42·124) topology. The results suggest that the reaction solvents, counter anions and metal-to-ligand ratios play important roles in the formation of frameworks. The complexes were characterized by X-ray crystallography and electrospray mass spectrometry. Complex 2 shows modest second harmonic generation (SHG) activity.

Design, synthesis, protein-ligand X-ray structure, and biological evaluation of a series of novel macrocyclic human immunodeficiency virus-1 protease inhibitors to combat drug resistance.

The structure-based design, synthesis, and biological evaluation of a series of nonpeptidic macrocyclic HIV protease inhibitors are described. The inhibitors are designed to effectively fill in the hydrophobic pocket in the S1'-S2' subsites and retain all major hydrogen bonding interactions with the protein backbone similar to darunavir (1) or inhibitor 2. The ring size, the effect of methyl substitution, and unsaturation within the macrocyclic ring structure were assessed. In general, cyclic inhibitors were significantly more potent than their acyclic homologues, saturated rings were less active than their unsaturated analogues and a preference for 10- and 13-membered macrocylic rings was revealed. The addition of methyl substituents resulted in a reduction of potency. Both inhibitors 14b and 14c exhibited marked enzyme inhibitory and antiviral activity, and they exerted potent activity against multidrug-resistant HIV-1 variants. Protein-ligand X-ray structures of inhibitors 2 and 14c provided critical molecular insights into the ligand-binding site interactions.

A theoretical IR spectroscopic study based on DFT calculations for free mn-15S 2O 3 maleonitrile-dithiacrown ether compound

The theoretically possible stable conformers of free mn-15S 2O 3 maleonitrile-dithiacrown ether molecule were searched by means of a conformational study which consists of molecular dynamics and energy minimization calculations performed with MM2 force field and successive geometry optimization + frequency calculations performed first at B3LYP/3-21G and then at B3LYP/6-31G(d) levels of theory. The obtained calculation results have clearly indicated that the free molecule in electronic ground state is very flexible and accordingly has many possible stable conformers of different conformational properties at room temperature; among them, the one having a macrocyclic ring structure in which all of the ether units oriented toward the center of the ring was determined the energetically most preferable conformer. In addition, the equilibrium geometrical parameters, vibrational normal modes and associated IR spectral data of the determined most stable three conformers of the molecule were calculated at B3LYP/6-31+G(d) and B3LYP/6-31++G(d,p) levels of theory. A successful assignment of the fundamental bands observed in the recorded experimental solid phase and solution phase IR spectra of the molecule was achieved in the light of the theoretical data obtained from these DFT calculations. To fit the calculated harmonic wavenumbers to the experimental ones, two different scaling procedures, referred to as “Scaled Quantum Mechanical Force Field (SQM FF) methodology” and “Scaling wavenumbers with empirical dual scale factors”, were proceeded independently.

Thermally Stable Gold(I) β-Diketiminate Complexes

The synthesis and X-ray structures of gold(I) adducts supported by beta-diketiminates have been reported. {[HC{(H)C(2,4,6-Br(3)C(6)H(2))N}(2)]Au}(2) and {[HC{(H)C(Dipp)N}(2)]Au}(2) [Dipp = 2,6-(i-Pr)(2)C(6)H(3)] are easily isolable solids and feature 12-membered macrocyclic ring structures. beta-Diketiminate ligands adopt a W-shaped conformation. Gold atoms are bonded to the nitrogen atoms in a linear fashion. (1)H NMR signals corresponding to the protons at the beta-diketiminate ligand beta-C position of the gold adducts appear at a notably high downfield region.