Mark Gerard Moloney

To better understand the properties of carbene and biscarbene species derived from bisdiazo compounds with varied terminal groups, a density functional theory (DFT) study was conducted on bisdiazo compounds with four terminal groups (bisdiazo‐X, where X=H, Me, NO ₂ and NH ₂ ) and their mono‐ and dicarbene derivatives. The studies included computation of their frontier molecular orbitals (FMOs), electronic structures, electrostatic potential (ESP) and polarity, as well as their IR and UV‐vis spectra and their color in THF solutions. For bisdiazo compounds at both ground and excited states, the computational results matched well with published experimental data. The formation of carbene species from bisdiazo compounds was confirmed via a generalized IRC path calculation and IGMH analysis. The reaction sites and the lone pair electron locations were predicted using minimum ESP (i.e., ESPmin) and orbital‐weighted Fukui dual descriptor for the possible intermediates in the transition state, along with spin density analysis through EPR/ESR predictions. Additionally, physisorption of bisdiazo and carbene species onto single‐layer graphene was evaluated through geometry optimization, in which π‐π stacking among the aromatic‐ring likely determines surface packing via the simulated scanning tunnelling microscope (STM) images. The carbene species permit controlled growth of the patterned functional organic surfaces.

The collapse of bisdiazo compounds with different terminal groups to generate reactive biscarbene intermediates has provided evidence for homopolymerization, in a process which proceeds in the absence of catalysts and is tolerant of oxygen.

While thiol-based adsorbates have achieved significant success in surface modification and molecular electronics, their thermal and storage instability has hindered long-term commercial viability. Carbene-based thin films offer a promising alternative due to their enhanced stability; however, their molecular electronic properties after postfunctionalization remain to be investigated. In this study, by attaching a ferrocene (Fc) unit to a bis(diarylcarbene)-modified gold surface via carbodiimide coupling, the system exhibits diode behavior with a current rectification ratio of ∼100. This diode behavior is highly temperature-dependent, indicating that hopping is the dominant mechanism for current rectification. Notably, the system demonstrated excellent electrical stability under ambient storage conditions for over 6 months. Our work highlights the potential for designing carbene-based molecular junctions through postmodification and for developing durable functional molecular electronic devices.

A chemoselective route which provides direct access to bicyclic tetramates, making use of Dieckmann cyclisation of functionalised oxazolidines and imidazolidines derived from an aminomalonate, is reported; calculations suggest that the observed chemoselectivity is kinetically controlled and leads to the thermodynamically most stable product. Some compounds in the library showed modest antibacterial activity against Gram-positive bacteria, and this activity is maximal in a well-defined region of chemical space (554 < M_w < 722 g mol⁻¹; 5.78 < cLogP < 7.16; 788 < MSA < 972 Ų; 10.3 < rel. PSA < 19.08).

A general route which provides direct access to substituted bicyclic tetramates, making use of Dieckmann cyclisation of oxazolidines derivatives derived from allo-phenylserines, is reported. Of interest is the high level of diastereoselectivity observed for the N-acylation reaction of oxazolidines and the complete chemoselectivity of their ring closure in the Dieckmann cyclisation. Significantly, the sense of the chemoselectivity is different to earlier reported threo-phenylserine systems, showing the importance of steric bulk around the bicyclic ring system. The derived C7-carboxamidotetramates, but not C7-acyl systems, exhibited potent antibacterial activity against MRSA, with the most active compounds exhibiting well-defined physicochemical and structure-activity properties. This work clearly demonstrates that densely functionalised tetramates are both readily available and may exhibit high levels of antibacterial activity.

The insertion of bis(diarylcarbene)s onto a glass fiber (GF) membrane surface provided an active coating for the direct capture of protein – exemplified by the enzyme, cellulase – through a mild diazonium coupling process which does not require additional coupling agents.

We report that phthalimides may be cyclized using a Mukaiyama-type aldol coupling to give variously substituted fused lactam (1,2,3,9b-tetrahydro-5H-pyrrolo[2,1-a]isoindol-5-one) systems. This novel process shows a high level of regioselectivity for o-substituted phthalimides, dictated by steric and electronic factors, but not for m-substituted phthalimides. The initial aldol adduct is prone to elimination, giving 2,3-dihydro-5H-pyrrolo[2,1-a]isoindol-5-ones, and the initial cyclisation can be conducted in such a way that aldol cyclisation-elimination is achievable in a one-pot approach. The 2,3-dihydro-5H-pyrrolo[2,1-a]isoindol-5-ones possess cross conjugation and steric effects which significantly influence the reactivity of several functional groups, but conditions suitable for epoxidation, ester hydrolysis and amide formation, and reduction, which provide for ring manipulation, were identified. Many of the derived lactam systems, and especially the eliminated systems, show low solubility, which compromises biological activity, although in some cases, antibacterial and cytotoxic activity was found, and this new class of small molecule provides a useful skeleton for further elaboration and study.

A general route, which provides direct access to substituted bicyclic tetramates, making use of Dieckmann cyclization of oxazolidines derived from threo-arylserines, is reported; the latter were found to be available by an efficient aldol-like reaction of glycine with some substituted benzaldehydes under alkaline conditions. The tetramates were found to release chelated metal cations acquired during chromatographic purification by mild acid wash. Some compounds in the library showed good antibacterial activity against Gram-positive bacteria. Cheminformatic analysis demonstrates that the most active compounds were Ro5-compliant and occupy a narrow region of chemical space, distinct from that occupied by other known antibiotics, with the most potent compounds having 399 < M_w < 530 Da; 3.5 < cLogP < 6.6; 594 < MSA 2; 9.6 < rel. PSA <13.3%. MIC values were shifted to higher concentrations when tested in the presence of HSA or blood, but was not completely abolished, consistent with a plasma protein binding (PPB) effect.