Therapeutic drug monitoring (TDM) is the clinical practice of measuring pharmaceutical drug concentrations in patients' biofluids at designated intervals, thus allowing a close and timely control of their dosage. To date, TDM in oncology can only be performed by trained personnel in centralized laboratories and core facilities employing conventional analytical techniques (e.g., MS). CPT-11 is an antineoplastic drug that inhibits topoisomerase type I, causing cell death, and is widely used in the treatment of colorectal cancer. CPT-11 was also found to directly inhibit acetylcholine esterase (AChE), an enzyme involved in neuromuscular junction. In this work, we describe an enzymatic biosensor, based on AChE and choline oxidase (ChOx), which can quantify CPT-11. ACh (acetylcholine) substrate is converted to choline, which is subsequently metabolized by ChOx to give betaine aldehyde and hydrogen peroxide. The latter one is then oxidized at a suitably polarized platinum electrode, providing a current transient proportional to the amount of ACh. Such an enzymatic process is hampered by CPT-11. The biosensor showed a ∼60% maximal inhibition toward AChE activity in the clinically relevant concentration range 10-10 000 ng/mL of CPT-11 in both simple (phosphate buffer) and complex (fetal bovine serum) matrixes, while its metabolites showed negligible effects. These findings could open new routes toward a real-time TDM in oncology, thus improving the therapeutic treatments and lowering the related costs.

An imine-linked (+)-syn-benzotricamphor derivative gives access to chiral unimolecular cages exhibiting internal cavities of new shapes and volumes. One of these hosts hydrocarbon gases at low temperatures in solution through CH-pi attractive interactions. No encapsulation is observed when the cage structure is too narrow or too large for the guest.

Therapeutic drug monitoring (TDM) is the clinical practice of measuring pharmaceutical drug concentrations in patients' biofluids at designated intervals to allow a close and timely control of their dosage. This practice allows for rapid medical intervention in case of toxicity-related issues and/or adjustment of dosage to better fit the therapeutic demand. Currently, TDM is performed in centralized laboratories employing instruments, such as immunoassay analyzers and mass spectrometers that can be run only by trained personnel. However the time required for the preparation, samples analysis, and data processing, together with the related financial cost, severely affects the application of TDM in medical practices. Therefore, a new generation of analytical tools is necessary to respond to the timely need of drug administration or reduction aiming at effectively treating oncologic patients. Technological advances in the field of nanosciences and biosensors offer the unique opportunity to address such issues. The interest for the so-called nanobiosensors is considerably increasing, particularly in drug discovery and clinical chemistry, even though there are only few examples reporting their use for TDM. The techniques employing nanobiosensors are mainly based on electrochemical, optical, and mass detection systems. In this review we described the most promising methodologies that, in our opinion, will bring TDM towards the next stage of clinical practice in the future.

SummaryTwo efficient protocols for the palladium-catalyzed synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides in the absence of copper were developed. A simple catalytic system consisting of Pd(OAc)2 and P(p-tol)3 using DBU as the base and THF as the solvent was found to be highly effective for the coupling reaction of 2-methyl-3-butyn-2-ol (4) with a wide range of aryl bromides in good to excellent yields. Analogously, the synthesis of aryl-2-methyl-3-butyn-2-ols was performed also through the decarboxylative coupling reaction of 4-hydroxy-4-methyl-2-pentynoic acid with aryl bromides, using a catalyst containing Pd(OAc)2 in combination with SPhos or XPhos in the presence of tetra-n-butylammonium fluoride (TBAF) as the base and THF as the solvent. Therefore, new efficient approaches to the synthesis of terminal acetylenes from widely available aryl bromides rather than expensive iodides and using 4 or propiolic acid rather than TMS-acetylene as inexpensive alkyne sources are described.

We report the integration of surface plasmon resonance (SPR), cyclic voltammetry and electrochemiluminescence (ECL) responses to survey the interfacial adsorption and energy transfer processes involved in ECL on aplasmonic substrate.I tw as observed that aT ween 80/tripropylamine nonionic layer formed on the gold electrode of the SPR sensor, while enhancing the ECL emission process,affects the electron transfer process to the luminophore,Ru(bpy) 3 2+ ,which in turn has an impact on the plasmon resonance.C oncomitantly,t he surface plasmon modulated the ECL intensity,w hich decreased by about 40 %, due to an interaction between the excited state of Ru(bpy) 3 2+ and the plasmon. This occurred only when the plasmon was excited, demonstrating that the optically excited surface plasmon leads to lower plasmonmediated luminescence and that the plasmon interacts with the excited state of Ru(bpy) 3 2+ within av ery thin layer.Surface plasmon resonance (SPR) [1] and electrogenerated chemiluminescence (ECL) [2] are increasingly employed for clinical analysis.B oth techniques rely on the concepts of biosensors,i nw hich capture molecules situated near the surface of the SPR chip or near the electrode in the case of ECL provides selectivity to the sensor.Hence,itwas revealed that SPR and ECL are complementary and offer similar performances for the detection of antibodies. [3] SPR sensors provide quantitative real-time information on the adsorption of molecules to as urface,a lthough the analysis of clinical samples in biofluids may be difficult. [4] ECL provides high sensitivity,h igh selectivity,a nd low detection limits even in crude matrices as it is relatively insensitive to nonspecific adsorption of biofluids,b ut lacks information on the adsorption processes occurring on the electrode.H ence,t he combination of SPR and ECL in as ingle instrument would be beneficial to monitor interfacial processes involved in ECL and to design biosensors with improved performances. To fully benefit from the combination of the techniques, at horough understanding of the underlying principles is needed. As they are both based on the electromagnetic properties of materials,s urface plasmons and luminophores can couple and give rise to enhanced chemiluminescence properties. [5] Analogous to the concept of metal-enhanced fluorescence, [6] in which the plasmon interaction with af luorophore enhances excitation and radiative relaxation pathways through the electromagnetic field of the plasmon, chemiluminescence [7] and electrochemiluminescence [8] can be enhanced by proximity to ap lasmonic substrate.I nt hese cases,the luminophore must be placed at adistance of about 10 nm to experience the greatest enhancement, which is on the order of 3-to 6-fold. [6c, 8, 9] At distances shorter than 10 nm, quenching of ECL was observed due to the energy transfer of the excited state of the luminophore to the metal surface.At greater distances,the plasmon enhancement decreases due to lower field enhancement. [6c, 8] In recent years,t he distance-depend...

The efficient aldol condensation between a derivative of methyl 3-hydroxy-5-oxohexanoate and a pyrimidinecarbaldehyde comprising the core structure of rosuvastatin has been developed as an alternative approach to the classical methods employing ylides for the synthesis of rosuvastatin.

In this work, a surface plasmon resonance (SPR)-based assay for the quantification of antineoplastic drug irinotecan in human plasma samples has been developed for the first time. The selective binding of irinotecan with an aptamer receptor, operating in human plasma, allowed to set-up a novel analytical methodology to detect the drug in the analytical range of interest by using SPR as detection technique. After hybridizing the aptamer to the sensing platform and optimizing the sample preparation procedure, a quantitative assay was validated according to FDA regulatory guidelines. The analytical working range was found between 100 and 7500 ng mL −1 with negligible interferences from plasma components and co-medication associated with the administration of irinotecan. The utility of the new SPR assay was confirmed by analyzing plasma samples in parallel with LC-MS as reference technique, providing a new analytical tool for the therapeutic drug monitoring of irinotecan in patients under chemotherapy regimens.

The synthesis of enantiopure (+)-benzotricamphor syn-5, an important chiral C3-symmetric rigid building block for supramolecular applications, was studied in detail to reduce the number of steps and to increase the diastereoselectivity and overall yield. The new synthetic procedure allowed larger amounts of syn-5 to be obtained and used for the preparation of new derivatives, such as the corresponding tris-trifluoromethanesulfonate syn-12, which was efficiently transformed into (+)-benzotribornenetrinitrile syn-1 and (+)-benzotribornenetris(ethynyl-4-pyridine) syn-2. The previously reported (+)-benzotricamphortrioxime syn-6 was transformed into tris-nitrile syn-3 by Beckman reaction. Compounds syn-1-3 were employed as multidentate ligands for silver(I) and platinum(II) centres in apolar solvents. The linear coordination geometry of Ag(I) and square-planar geometry of cis-chelated Pt(II) in combination with the chiral tripodal ligands syn-1-3 led to the formation of chiral enantiopure capsules with M3 L2 stoichiometry, as confirmed by 2D NMR NOESY and DOSY experiments as well as ESI mass spectrometry.