Prodrugs of acyclovir--a computational approach.

Density functional theory calculation results demonstrated that the efficiency of the acid-catalyzed hydrolysis of Kirby's acid amides 1-15 is strongly dependent on the substitution on the C-C double bond and the nature of the amide N-alkyl group. Further, the results established that while in the gas phase the hydrolysis rate-limiting step is the tetrahedral intermediate formation in polar solvents such as water, the rate-limiting step could be either the formation or the collapse of the tetrahedral intermediate depending on the substitution on the C-C double bond and on the amide nitrogen substituent. Based on a linear correlation between the calculated and experimental effective molarities, the study on the systems reported herein could provide a good basis for designing prodrug systems that are less hydrophilic than their parental drugs and can be used, in different dosage forms, to release the parent drug in a controlled manner. For example, based on the calculated log effective molarities values, the predicted t(1/2) (a time needed for 50% of the reactant to be hydrolyzed to products) for acyclovir prodrugs, ProD 1-4, was 29.2 h, 6097 days, 4.6 min, and 8.34 h, respectively. Hence, the rate by which acyclovir prodrug releases acyclovir can be determined according to the structural features of the linker (Kirby's acid amide moiety).

Neighbors and enemies: lessons to be learned from the Palestinian-Israeli conflict regarding cooperation in public health.

We aim to demonstrate on the example of recent Palestinian-Israeli collaborative projects how sustainable cooperation can be achieved despite unfavorable political atmosphere and continuing violent disputes. Palestinian and Israeli participants of the collaborative projects declared that their attitude and belief in coexistence was positively changed as a result of their experience in cooperative work. Their main motivations were a desire to contribute to the resolution of the conflict and to improve professional skills. The experience in Israeli-Palestinian conflict showed that the collaborative projects of higher chance of success and sustainability should address issues of high priority to the concerned parties, lead to demonstrable benefits in the immediate future, and preferably be organized by non-governmental organizations. Also, to secure long-term success of collaborative projects, parity and symmetry should be maintained, as well as equal division of work and responsibility between the partners. Collaboration in public health field is first to be (re)established in conflict areas to alleviate suffering, minimize future health risks, and prevent further health deterioration. Thereby, public health can serve as a bridge to peace in areas of unrest or war.