Contribution of H-Bonding to the Preference of Platinum Anti-Tumour Drugs for Particular Bases and Particular Cross-Links

The stereochemical factors that influence the tendencies for sequence specific binding of platinum antitumour drugs to DNA are examined. The NHs of the platinum-amine moiety can form hydrogen bonds to the O6 of guanine or to a phosphate oxygen of DNA. Modelling the stereochemistry of the NH atoms can lead to compounds with a strong preference for forming one type of adduct with DNA

Reaction of cis- and trans-Dichlorotetra(Dimethylsulfoxide)Ruthenium(II) With the Antiviral Drug Acyclovir

NMR was used to investigate the reaction of cis- and trans-[RuCl2(DMSO)4] with the antiviral drug acyclovir, a guanine derivative containing the acyclic (2-hydroxo) ethoxymethyl pendant linked to N(9). Studies were performed in aqueous solutions at ambient temperature and at 37 °C, and at various molar ratios. Both isomers yielded two compounds, a monoadduct and a bisadduct, the relative yields being dependent upon the metal to ligand concentration ratios. The products derived from the two Ru isomers displayed identical NMR spectra, suggesting that they have the same coordination environment, however the rate of formation of the monoadduct was higher in the case of the trans isomer than in the case of the cis isomer, while the rate of conversion of the monoadduct into the bisadduct appeared to be similar in both cases. As a consequence in the case of the trans isomer there is accumulation of monoadduct in the early stage of the reaction, whose concentration afterwards decreases with the progress of the reaction. As for platinum, also for ruthenium the preferred binding site is N(7) of the purine base, however, in the case of ruthenium a discrete amount of bisadduct is formed even in the presence of an excess of metallic substrate with respect to the acyclovir ligand; under similar conditions a platinum substrate would have given, nearly exclusively, the monoadduct

Contraction of general transportation costs along solutions to Fokker-Planck equations with monotone drifts

We shall prove new contraction properties of general transportation costs along nonnegative measure-valued solutions to Fokker-Planck equations in Rd, when the drift is a monotone (or lambda-monotone) operator. A new duality approach to contraction estimates has been developed: it relies on the Kantorovich dual formulation of optimal transportation problems and on a variable-doubling technique. The latter is used to derive a new comparison property of solutions of the backward Kolmogorov (or dual) equation. The advantage of this technique is twofold: it directly applies to distributional solutions without requiring stronger regularity and it extends the Wasserstein theory of Fokker-Planck equations with gradient drift terms started by Jordan-Kinderlehrer-Otto [14] to more general costs and monotone drifts, without requiring the drift to be a gradient and without assuming any growth conditions

Regulating Exclusions? Gender, Development and the Limits of Inclusionary Financial Platforms

Digital financial inclusion platforms have gained increasing attention as instruments for economic growth which also contribute to development goals such as poverty reduction and gender equality. One of the most acclaimed digital financial platforms to date is M-Pesa (M for mobile, pesa, Swahili for money) in Kenya, a mobile-phone-enabled money transfer service realised via a public-private partnership between the UK’s Department for International Development, Vodafone and its local partner Safaricom. Since its launch in 2007 M-Pesa has grown at a phenomenal rate and it is now used by over 70 per cent of the Kenyan population. Bringing together socio-legal enquiry, feminist political economy analysis and postcolonial literature, this paper discusses M-Pesa’s inclusionary regulatory arrangements and examines their implications for gender equality. It shows that while these arrangements contribute to including women in the formal financial system, they fail to adopt the redistributive measures necessary to address the gendered socio-economic disadvantages that cause and reproduce financial exclusion

Digital finance and the mobile money “social” enterprise : a socio-legal critique of M-Pesa in Kenya

Financial technology or fintech initiatives are gaining increasing global attention as instruments for financial inclusion and economic and social development. Among such initiatives, mobile-phone-enabled money transfer systems, or “mobile money”, have been particularly acclaimed for facilitating access to financial services and creating opportunities for the so-called “unbanked poor”. One of the first and most-discussed mobile money projects to date is M-Pesa in Kenya, a digital payment system which is now used by over 70 per cent of the Kenyan population across a variety of sectors including finance, commerce, education, health, and social welfare. M-Pesa is premised on a narrative of social entrepreneurship and has increasingly embraced the idea of philanthrocapitalism, promoting the logic that digital financial inclusion can simultaneously address social problems and produce profit. This paper brings together socio-legal enquiry and international political economy analysis to illustrate the institutional arrangements underpinning the development of M-Pesa and examine some of the projects built on its infrastructure. It argues that social entrepreneurship promotes a logic of opportunity rather than a politics of redistribution, favouring mobile money providers and the institutions involved in the mobile money social business over improving the lives of the intended beneficiaries, namely the unbanked poor

Digital Finance Inclusion and the Mobile Money “Social” Enterprise: A Socio-Legal Critique of M-Pesa in Kenya

Special Issue: Social Finance, Impact Investing, and the Financialization of the Public Interes

“Lantern-Shaped” Platinum(III) Complexes with Axially Bound 9-Ethylguanine or 1-Methylcytosine (L) of General Formula [Pt2{HN=C(But)O}4L2](NO3)2

The synthesis, NMR characterization, and X-ray crystallography of “lantern-shaped” platinum(III) complexes with four pivaloamidate bridging ligands and two 9-ethylguanines (9-EtG) or 1-methylcytosines (1-MeC) in axial positions are reported: cis-N2O2-[Pt2{HN=C(But)O}4(9-EtG)2](NO3)2 and cis-N2O2-[Pt2{HN=C(But)O}4(1-MeC)2](NO3)2. The last complex is, to the best of our knowledge, the first dinuclear compound of platinum(III) with axially bound 1-MeC

Chiral discrimination in platinum anticancer drugs.

In this article we review the biological activity of analogs of the antitumor drug cisplatin that contain chiral amine ligands. Interaction with DNA and formation of cross-links with adjacent purine bases are considered to be the crucial steps in the antitumor activity of this class of complexes. Because double-helical DNA has a chiral structure, interaction with enantiomeric complexes of platinum should lead to diastereomeric adducts. It has been demonstrated that DNA cross-links of platinum complexes with enantiomeric amine ligands not only can exhibit different conformational features but also can be processed differently by the cellular machinery as a consequence of these conformational differences. These results expand the general knowledge of how the stereochemistry of the platinum-DNA adduct can influence the cell response and contribute to understanding the processes that are crucial for antitumor activity. The steric requirements of the chiral ligands, in terms of configuration and flexibility, are also elucidated

Platinum(II)-Acyclovir Complexes: Synthesis, Antiviral and Antitumour Activity

A platinum(II) complex with the antiviral drug acyclovir was synthesized and its antiviral and anticancer properties were investigated in comparison to those of acyclovir and cisplatin. The platinum-acyclovir complex maintained the antiviral activity of the parent drug acyclovir, though showing a minor efficacy on a molar basis (ID50  =   7.85 and 1.02 μΜ for platinum-acyclovir and cisplatin, respectively). As anticancer agent, the platinum-acyclovir complex was markedly less potent than cisplatin on a mole-equivalent basis, but it was as effective as cisplatin when equitoxic dosages were administered in vivo to P388 leukaemia-bearing mice (%T/C = 209 and 211 for platinum-acyclovir and cisplatin, respectively). The platinum-acyclovir complex was also active against a cisplatin-resistant subline of the P388 leukaemia (%T/C = 140), thus suggesting a different mechanism of action. The DNA interaction properties (sequence specificity and interstrand cross-linking ability) of platinum-acyclovir were also investigated in comparison to those of cisplatin and [Pt(dien)Cl]+, an antitumour-inactive platinum-triamine compound. The results of this study point to a potential new drug endowed, at the same time, with antiviral and anticancer activity and characterized by DNA interaction properties different from those of cisplatin